Triple negative breast cancer: Deciphering the biology and heterogeneity

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The figure shows the structural and nonstructural proteins the way they are organized throughout the genome as well as the untranslated regions in 5′ and 3′. The name, size in amino acids and function is showed for each protein. The figure is drawn to scale based on the reference ZIKV genome with GenBank access number: <a class="elsevierStyleInterRef" id="intr0005" href="ncbi-n:NC_012532.1">NC_012532.1</a>.<a class="elsevierStyleCrossRef" href="#bib0450">13</a> The information regarding viral protein function was obtained from the UniProt database using dengue virus due to the lack of published data. The accession number used was P17763.<a class="elsevierStyleCrossRef" href="#bib0770">77</a> NS: nonstructural protein; C: capsid; E: envelope; prM: precursor membrane; UTR: untranslated region; Kb: kilobases." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "K.A. Galán-Huerta, A.M. Rivas-Estilla, E.A. Martinez-Landeros, D. Arellanos-Soto, J. Ramos-Jiménez" "autores" => array:5 [ 0 => array:2 [ "nombre" => "K.A." "apellidos" => "Galán-Huerta" ] 1 => array:2 [ "nombre" => "A.M." "apellidos" => "Rivas-Estilla" ] 2 => array:2 [ "nombre" => "E.A." "apellidos" => "Martinez-Landeros" ] 3 => array:2 [ "nombre" => "D." "apellidos" => "Arellanos-Soto" ] 4 => array:2 [ "nombre" => "J." "apellidos" => "Ramos-Jiménez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665579616300588?idApp=UINPBA00004N" "url" => "/16655796/0000001800000071/v1_201608180032/S1665579616300588/v1_201608180032/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S1665579616300618" "issn" => "16655796" "doi" => "10.1016/j.rmu.2016.06.001" "estado" => "S300" "fechaPublicacion" => "2016-04-01" "aid" => "75" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "ssu" "cita" => "Medicina Universitaria. 2016;18:98-104" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2243 "formatos" => array:3 [ "EPUB" => 55 "HTML" => 1837 "PDF" => 351 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Bases and foundations of the treatment of peritoneal carcinomatosis: Review article" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "98" "paginaFinal" => "104" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1531 "Ancho" => 947 "Tamanyo" => 247038 ] ] "descripcion" => array:1 [ "en" => "Coliseum technique, with placement of influx and drainage tubes and temperature sensors." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.F. Castro-Mesta, J.F. González-Guerrero, P. Barrios-Sánchez, G. Villarreal-Cavazos" "autores" => array:4 [ 0 => array:2 [ "nombre" => "J.F." "apellidos" => "Castro-Mesta" ] 1 => array:2 [ "nombre" => "J.F." "apellidos" => "González-Guerrero" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Barrios-Sánchez" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "Villarreal-Cavazos" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665579616300618?idApp=UINPBA00004N" "url" => "/16655796/0000001800000071/v1_201608180032/S1665579616300618/v1_201608180032/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Triple negative breast cancer: Deciphering the biology and heterogeneity" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "105" "paginaFinal" => "114" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "G.I. Uscanga-Perales, S.K. Santuario-Facio, R. Ortiz-López" "autores" => array:3 [ 0 => array:3 [ "nombre" => "G.I." "apellidos" => "Uscanga-Perales" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "S.K." "apellidos" => "Santuario-Facio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "R." "apellidos" => "Ortiz-López" "email" => array:1 [ 0 => "rortizlopez@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Genómica, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León, Monterrey, Mexico" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at: Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Av. Francisco I. Madero y Dr. Eduardo Aguirre Pequeño, s/n Col. Mitras Centro, Monterrey, N.L. C.P. 64460, Mexico. Tel.: +52 81 83485287; fax: +52 81 83337747." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1400 "Ancho" => 2595 "Tamanyo" => 226783 ] ] "descripcion" => array:1 [ "en" => "Lehman's triple negative breast cancer classification, gene ontology and proportion. TNBC, triple negative breast cancer; BL1, basal like 1; BL2, basal like 2; IM, immunomodulatory; M, mesenchymal; MSL, mesenchymal stem cell-type; LAR, androgen luminal receptor; MET, mesenchymal epithelial transition." ] ] ] "textoCompleto" => "IntroductionBreast cancer (BC) is the main cause of death by cancer among women, and represents 30% of all new cancer cases in the Caucasian population. A woman living in the United States has a 12.3% (1 in every 8) risk of being diagnosed with breast cancer.<a class="elsevierStyleCrossRef" href="#bib0390">1</a> According to the World Health Organization, 1.67 million new cases were registered worldwide in 2012.<a class="elsevierStyleCrossRef" href="#bib0395">2</a> In Mexico, BC is also the first place in malignant neoplasia incidence among women. It represents 11.34% of all cancer cases, with a global increase of approximately 1.5% annually. However, in emerging countries this increase is up to 5%.<a class="elsevierStyleCrossRef" href="#bib0400">3</a>Despite having the same origin tissue, BC represents a heterogeneous cancer group with complex biological behavior and a great clinical variability. Over the last 10 years, extensive research at a molecular and genetic level has been conducted in order to sub-type these BCs. This has permitted the determination of clinical, pathological and molecular variables, to select treatment modalities and forecast, in some cases, the evolution of the disease at the moment of diagnosis.<a class="elsevierStyleCrossRef" href="#bib0405">4</a>Breast cancer classificationIn the traditional way the most important information that pathologists gave oncologists, respect to the classification of breast cancer, included the status of the nodules and tumor size, histological grade and standard immunohistochemistry tests (IHC) status of hormone receptors: estrogen receptor (ER) and progesterone receptor (PR) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Later on, in the era of trastuzumab, information on the amplification status of the human epidermal growth factor receptor 2 gene (HER2) became routine. Combining all these parameters, it was possible to classify patients as high or low risk. There were however a group of patients who were in an intermediate category that could not be classified between these two groups. Results showed that 15% of the patients classified as low risk had relapsed or died due to a very aggressive disease. And patients classified as high risk, surprisingly 10–15% had a favorable response. All those results led to the conclusion that the method of classification was not very appropriate.Thus, based only on standard IHC directed at cellular markers that reflect the availability of targeted therapies, breast cancer can also be classified into three main groups: (a) homone sensitive (ER or PR positive), (b) HER2 positive, sensitive to trastuzumab or (c) triple negative breast cancer (TNBC), defined by the absence of ER, PR and HER2 amplification.<a class="elsevierStyleCrossRefs" href="#bib0410">5–8</a>No targeted treatment is available for TNBT and chemotherapy remains the best therapeutic option. However, in the case of recurrence or chemoresistance, therapeutic options are very limited.<a class="elsevierStyleCrossRef" href="#bib0430">9</a>Subsequently, in the late 90s, when platforms for genomic studies were available, IHC methods coupled with complementary DNA (cDNA) microarray technology, allowed for a more extensive BC classification and were able to define four different BC subgroups, which differ in prognosis and targets: (a) luminal A – positive to ER and PR, negative to the amplification of HER2, with a low proliferation index (Ki-67<14%); (b) luminal B – ER positive, HER2 positive or negative, high proliferation index (Ki-67>14%), negative or low positive PR; (c) positive for HER2 – overexpressed or amplified HER2, negative ER and PR; (d) basal-like or TNBC, also defined by the absence of ER, PR and HER2 amplification. However, this last assumption is not strictly accurate due as not all basal-like tumors are completely TNBC.<a class="elsevierStyleCrossRefs" href="#bib0435">10,11</a>This classification is based on the consideration that there are two cell types in the mammary gland, luminal cells and basal cells. These two cell types can be differentiated by IHC tests as luminal cells, which express ER and PR and that are positive for keratins 8/18, while basal cells are positive for keratins 5/6 and 17.<a class="elsevierStyleCrossRefs" href="#bib0445">12,13</a>Because of the cost involved in utilizing microarray technology in the clinic, the most employed technique for BC classification remains IHC and FISH.<a class="elsevierStyleCrossRefs" href="#bib0415">6,8,14</a>Between 60% and 70% of all breast cancers correspond to positive ER and PR subtypes,<a class="elsevierStyleCrossRef" href="#bib0415">6</a> which usually respond to targeted ER therapy, such as selective ER modulators (i.e. tamoxifen, or aromatase inhibitors) which reduce serum estrogen concentrations. Around 15–20% of BCs amplify or overexpress the HER2 oncogene. This type of cancer is associated with an incorrect prognosis and the treatments specifically aimed at HER2 (i.e. trastuzumab) have greatly improved results in women with BC HER2+.<a class="elsevierStyleCrossRef" href="#bib0460">15</a>Prognostic value of genomic signatures in BCDespite the fact that they have not completely turned into routine methods, genomic methods have been used in research studies with the purpose of: (a) getting a better understanding of the nature of these variations of BC; (b) stratifying patients through assessment of the evolution of the disease (evaluating clinical pathological characteristics), and (c) understanding the possible response of the patient to treatment (in relationship with ER, PR, HER2 and the proliferation rate).<a class="elsevierStyleCrossRefs" href="#bib0410">5,16</a>Through global expression analysis with microarrays, the identification of gene groups (genomic signatures) has been possible, which allow us to estimate risk of recurrence of the disease and/or predict the response to adjuvant therapy in BC patients in the early stages.<a class="elsevierStyleCrossRefs" href="#bib0470">17–20</a> Some of these genomic signatures have been validated in large cohorts and have been the precedent for some commercial genomic tests, providing complementary information to clinicians in order to obtain a more precisely classification patients who has a high risk of recurrence, and to offer more personalized attention.The first commercial signature, and the one still widely distributed under its commercial name, is MammaPrint® (Agilent, Amsterdam, Holland). This signature measures mRNA of 70 gene expression and was approved by the US FDA and by regulators in the EU as an essay with prognostic value in patients with BC who are under 61 years of age, in an I/II stage, with negative lymph nodes or one to three positive lymph nodes. In addition to accurately identifying patients who can safely avoid adjuvant chemotherapy.<a class="elsevierStyleCrossRefs" href="#bib0470">17,21</a> MammaPrint stratifies patients into low-risk or high-risk groups.<a class="elsevierStyleCrossRef" href="#bib0470">17</a> However, even though discrimination is good for ER+ cancers, it is not the same with ER− cancers,<a class="elsevierStyleCrossRefs" href="#bib0495">22,23</a> limiting its clinical value to a subgroup of patients.Another widely distributed and commercially available assay is Oncotype DX® test (Genomic Health, Redwood City, CA, U.S.). This test is used to classify patients with Luminal A and B BCs, as well as HER2+ subtypes (though not TNBC), since it has been designed to assess genes related to ER, proliferation genes, HER2 genes, and genes related to invasion, among others.<a class="elsevierStyleCrossRef" href="#bib0480">19</a> This test allows the oncologist to discern whether or not chemotherapy treatment will be beneficial. This essay measures the 21-gene expression, which provides information of the recurrence of the disease through a scoring system from 0 to 100, stratifying patients into low-risk (score <18), intermediate risk (score 18–30) or high risk (≥31) groups.<a class="elsevierStyleCrossRefs" href="#bib0480">19,20</a>A third test, consisting of an algorithm for the intrinsic molecular classification of BC, has been nominated PAM50 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). This was designed to improve IHC and microarray classification aggreance.<a class="elsevierStyleCrossRef" href="#bib0505">24</a> This 50-gene signature can classify BCs as luminal A, luminal B, HER2 and basal-like. The PAM50 score was designed with the purpose of translating the different intrinsic subtypes into an associated prognostic value.<a class="elsevierStyleCrossRef" href="#bib0505">24</a> An application of this score is the identification of patients who may benefit from the weekly addition of paclitaxel to conventional chemotherapy with anthracycline as an adjuvant treatment of operable BC with positive lymph nodes.<a class="elsevierStyleCrossRef" href="#bib0510">25</a> In 2013, Prosigna (Seattle, Washington, U.S.) started commercializing a diagnostic kit which qualifies mRNA expression of the 50 genes used by the algorithm in order to calculate the risk of recurrence.<a class="elsevierStyleCrossRef" href="#bib0515">26</a><elsevierMultimedia ident="fig0010"></elsevierMultimedia>In addition to these tests, which are the most commonly distributed, there are others in the market,<a class="elsevierStyleCrossRefs" href="#bib0520">27–29</a> where the common denominator is the measurement of gene expression of proliferation related genes. It is important to mention that these multiple-gene assays are for the most part, if not exclusively, applicable to luminal BC, thus stressing once more the need to search for and identify markers with prognostic value and response to treatment in BC patients with negative hormonal receptors or HER2 amplification.Triple negative breast cancer (TNBC)Since 1997, the National Comprehensive Cancer Network (NCCN) has gathered data of women with newly diagnosed breast cancer, representing many institutions around the U.S. HER2 by IHC's status was added to the data from the NCCN as a routine element in the year 1999, and HER2 status through fluorescent in situ hybridization (FISH) was added in 2001. The term “Triple Negative Breast Cancer” (TNBC) appeared for the first time in the literature in 2005.<a class="elsevierStyleCrossRef" href="#bib0535">30</a> Due to the lack of effective therapeutic options, many studies have focused on the understanding of the biology of TNBC for the selection of biomarkers and therapeutic targets. In this review, we will focus on making a compilation of molecular and gene studies in reference to this BC subgroup.TNBC risk factorsTNBC makes up about 15–20% of all BCs and follows an aggressive clinical course, including a high incidence of visceral and nervous metastases, compared to BCs positive to hormone receptors, TNBC is more frequently associated with BRCA1 and, to a lesser extent, BRCA2 mutations.<a class="elsevierStyleCrossRefs" href="#bib0540">31,32</a> It has also been associated with a high local recurrence rate at three years after treatment, and a high death rate at 5 years. Upon long-range metastasis, the survival rate is poor.<a class="elsevierStyleCrossRef" href="#bib0550">33</a> Differently from other subtypes of BC (Luminal A, B and HER2), where early pregnancy has been recognized as a protective factor against BC, gestation appears to be an important risk factor in the development of the triple negative phenotype. In a study by Phipps et al.,<a class="elsevierStyleCrossRef" href="#bib0555">34</a> they reported that women who had more children (three or more) had a greater risk (1.4 times) of TNBC. Later, a study by Tamimi et al.<a class="elsevierStyleCrossRef" href="#bib0560">35</a> reaffirmed that multiple pregnancies were associated with an increased risk of developing TNBC.Other behaviors associated with the triple negative subtype are a lack of lactation,<a class="elsevierStyleCrossRef" href="#bib0565">36</a> and various studies have made an association between TNBC and a high body mass index (BMI), a metabolic syndrome, type 2 diabetes, obesity and/or insulin resistance.<a class="elsevierStyleCrossRefs" href="#bib0570">37–43</a> Consequently, patients with TNBC are the group with the worst prognosis, which is important to consider in a country like Mexico, which has an elevated prevalence of obesity and metabolic syndrome.Racial ancestry has been shown to have an important relation to TNBC, since 21% of Afro American BCs have been classified as TNBC (compared to 15% of the Caucasian population).<a class="elsevierStyleCrossRefs" href="#bib0605">44–46</a> The Hispanic population has also shown a high incidence of this cancer subtype, with a frequency of 21.3% in Peru,<a class="elsevierStyleCrossRef" href="#bib0620">47</a> 27% in Brasil,<a class="elsevierStyleCrossRef" href="#bib0625">48</a> 24.1% in Venezuela<a class="elsevierStyleCrossRef" href="#bib0630">49</a> and 23.1% in Mexico.<a class="elsevierStyleCrossRef" href="#bib0635">50</a>TNBC presents a high rate of proliferation<a class="elsevierStyleCrossRef" href="#bib0640">51</a> and is highly aggressive.<a class="elsevierStyleCrossRefs" href="#bib0545">32,52–54</a> In a study by Sorlie et al., in which the response to an uniform treatment was evaluated, they reported differing results between patients belonging to groups of distinct subtypes. Among these results exist a report that patients with TNBC had the worst prognosis by a significant margin when compared to patients with cancers that had positive hormone receptors.<a class="elsevierStyleCrossRef" href="#bib0440">11</a> In a later study, Dent et al. compared the clinical history, outcome and the nature of the disease in women with TNBC to women with other subtypes. The results showed that TNBC had a low survival rate and a high rate of long-distance metastasis after treatment.<a class="elsevierStyleCrossRef" href="#bib0645">52</a> Due to TNBC's aggressive course, these types of cancers can be highly sensitive to cytotoxic medications. The proportion of patients who reach a complete pathological response (CPR) after treatment were found to be 30–45%,<a class="elsevierStyleCrossRefs" href="#bib0660">55,56</a> and the patients, which achieved a CPR had excellent long-term results, with a global survival rate higher than 90%. In addition, if CPR is achieved, patients with TNBC or other types of BC had a similar survival rate. However, those patients with TNBC who presented with a residual disease had worse results than patients with other types of BC.<a class="elsevierStyleCrossRefs" href="#bib0610">45,57</a> The aggressiveness of TNBC and the shortage of specific therapeutic options underline the need to understand the ways in which this type of cancer develops.Molecular classification of TNBC subtypesIn 2007, Kreike et al. reported that TNBCs were synonymous with basal type molecular cancers.<a class="elsevierStyleCrossRef" href="#bib0675">58</a> However, as we mentioned before, it has been proven that TNBC's molecular biology is diverse and heterogenous,<a class="elsevierStyleCrossRef" href="#bib0680">59</a> and that TNBC is not an ideal substitute for the basal phenotype. In 2011, Lehmann et al.<a class="elsevierStyleCrossRef" href="#bib0685">60</a> identified 6 subtypes of TNBC, as well as 1 unstable subtype. The six subtypes included two basal like (BL1 and BL2), one immunomodulatory class, one mesenchymal class, one mesenchymal stem cell (MSC) class, and one luminal androgen receptor (LAR) class. In addition, gene expression analysis allowed the authors to identify the cell lines representative of each TNBC subtype to later evaluate their response to different medications.<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">BLI: Cancers in this group are characterized by their rapid cell division, with an increased proliferation rate and loss of cell cycle control. Due to this, they present an elevated expression (mRNA) of Ki67 and respond to antimitotic agents.</li><li class="elsevierStyleListItem" id="lsti0010">BL2: These cancers present the expression of EGFR, TP63, MET, etc. and involve activation of glycolysis and gluconeogenesis routes.</li><li class="elsevierStyleListItem" id="lsti0015">IM: They are composed of response cells from the immune system, and present antigens and cytokine expression. They overlap with medullary breast cancer with a favorable prognosis.</li><li class="elsevierStyleListItem" id="lsti0020">M and MSL: These groups present epithelial-mesenchymal transition markers, including angiogenesis (VEGFR2) and most likely respond to desatinib (TK inhibitors) and mTOR.</li><li class="elsevierStyleListItem" id="lsti0025">LAR: This group is characterized by the expression of androgen receptors (AR). They are RE negative, but maintain an elevated hormonal component, regulated by steroid synthesis, porphyrin metabolism genes and androgens/estrogens. The AR's expression is up to nine times more than the other groups, and are prime candidates for anti-androgen therapies.</li></ul>The signaling pathways obtained by the study are potential pharmacological targets in these cell models to that analysis of these distinct genetic signatures can be used to select a therapy. In general, it was observed that the BL1 and BL2 subtypes respond well to cisplatin, and that the M and MSL types respond well to NVP-BEZ235, a PI3K/mTOR inhibitor and dasatinib (a tyrosine kinase inhibitor). The LAR subtype was only sensitive to bicalutamide (an androgen receptor agonist).Later, Burstein et al.<a class="elsevierStyleCrossRef" href="#bib0690">61</a> confirmed four of the subtypes reported by Lehmann with the base DNA profiles or the single nucleotide DNA markers from 198 TNBC samples: one luminal androgen receptor type, one mesenchymal type, and two basal types. These studies by Burstein and Lehmann suggested the existence of at least 4 TNBC subtypes (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>The search for TNBC biomarkersVarious expression studies have been performed on TNBC with the aim of identifying therapeutic targets, which have been summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. This summary includes the characteristics of each study and the selected differentially expressed principal genes. This table shows the variability of the data obtained from each study. This indicates that validation of these possible molecular targets is necessary and even more studies are required to find efficient biomarkers for the treatment of TNBC.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>TNBC is a subtype of BC with a very heterogeneous behavior which, based on gene expression analysis by microarray, was classified by Lehmann into six distinct groups. This sub-classification is not only useful to the better understanding of this disease, but also to identify new molecular targets for its treatment. Following are some of the proteins which have been identified in these TNBC groups as potential therapeutic targets.<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030">EGFR: This is one of the principal receptors, and plays an important role in the survival of the tumor. It is a marker of cellular proliferation, angiogenesis, metastasis and apoptosis inhibition.</li><li class="elsevierStyleListItem" id="lsti0035">VEGF: This is the principal marker for angiogenesis. It induces proliferation and maintains the integrity of the cell.</li><li class="elsevierStyleListItem" id="lsti0040">C-kit and basal cytokeratins: C-kit unites with the receptor of a growth factor, stimulates survival and differentiation, and induces invasiveness in the cancerous cell. The basal cytokeratins are intermediate filament proteins. Their expression is constant when epithelium undergoes transformation.</li><li class="elsevierStyleListItem" id="lsti0045">P53: suppressor protein important in cell cycle regulation and tumor apoptosis.</li><li class="elsevierStyleListItem" id="lsti0050">hKi67: A cellular proliferation marker which is present in the nucleus during interphase and mitosis. Ki67 expression in normal mammary tissue is <3%. The expression of TNBC can elevate it up to 80%. It self-expresses particularly in RE-negative cells. It is associated with an unfavorable prognosis.</li><li class="elsevierStyleListItem" id="lsti0055">PARP: A family of cell signaling enzymes. 18 PARP proteins have been identified. PARP1 is responsible for the majority of its functions. It is a DNA damage sensor and plays an important role in its repair and in responses to inflammation, ischemia and oxidative stress. In cells with a BRCA mutation, PARP inhibition contributes to cell death by apoptosis.</li><li class="elsevierStyleListItem" id="lsti0060">Hsp90: A cellular chaperone, it stabilizes the conformation of many labile proteins, such as steroid receptors, CDK4, RAF-1 and AKT, etc. PU-H71 is a cyclin inhibitor which has been shown to be useful in some TNBC models.</li><li class="elsevierStyleListItem" id="lsti0065">COX2: This protein is expressed by the inflammatory stimulus and its expression is associated with an unfavorable prognosis.</li><li class="elsevierStyleListItem" id="lsti0070">TK: A regulatory protein which helps the cell grow and differentiate itself.</li><li class="elsevierStyleListItem" id="lsti0075">mTOR: The over-expression of these proteins (PI3K/mTOR) is associated with a poor response to treatment with hormones and trastuzumab.</li></ul>TNBC treatmentWomen with TNBC are not able to take endocrinology therapies neither HER2 targeted therapies, hence treatment options are limited to surgery, radiotherapy and chemotherapy,<a class="elsevierStyleCrossRefs" href="#bib0695">62,63</a> being chemotherapy the standard treatment of TNBC. In the past two decades the use of more aggressive therapy has produced a clearer improvement in quality of life; however, there is a consensus opinion, which considers that it would be impossible to improve these results if this cytotoxic therapy remained the only option to be offered to these patients. For this reason, there is an urge to find new “intelligent drugs” capable of solving chemoresistance and reducing the risks of chemotherapy in patients who do respond. The greatest obstacle to find actionable targets is the vast heterogeneity both inter and intra-tumor of the TNBC. In fact, several years of study have failed to prove a unified alteration which may serve as targets of a targeted therapy.Several researches about TNBC describe genomic signatures involving affected signaling pathways, including cellular, immunologic and metabolic processes like – basal keratin differential expressions, interferon proliferation and regulation routes, low expression in Claudine, mesenchymal epithelial transition, androgen receptor expression (AR) and angiogenesis activation (VEGF).<a class="elsevierStyleCrossRefs" href="#bib0675">58–60</a> These findings have revealed potential molecular targets,<a class="elsevierStyleCrossRef" href="#bib0630">49</a> and different drug types are currently found under investigation, which can basically be defined in four groups: (1) agents which cause damage to DNA (i.e. cisplatin, cyclophosphamide), (2) agents which inhibit poly (ADP-ribose) polymerase (PARP inhibitors), (3) tyrosine-kinase inhibitors and (4) agents which inhibit downstream signaling pathways (mainly PI3K/AKT).<a class="elsevierStyleCrossRef" href="#bib0705">64</a> Down below there are the descriptions of treatments which have been proven depending upon identified therapeutic targets in TNBC.<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0080">•Bevacizumab: Anti-VEGF (vascular endothelial growth factor) monoclonal antibody that blocks angiogenesis; although, a lack of efficiency as well as a toxicity increment have been observed.<a class="elsevierStyleCrossRef" href="#bib0710">65</a></li><li class="elsevierStyleListItem" id="lsti0085">•Olaparib/iniparib: PARP inhibitors in patients with mutations in BRCA1/2, they have also been widely studied since they have shown to have anticancer selective activity in BRCA1 and BRCA2-deficient cancers; nevertheless, the relevance of the inhibition of these enzymes has yet to be confirmed.<a class="elsevierStyleCrossRef" href="#bib0715">66</a></li><li class="elsevierStyleListItem" id="lsti0090">•Cetuximab: Anti-EGFR monoclonal targeted antibody, it has been evaluated as monotherapy or with a platinum-based therapy (carboplatin). Even though, at first, this therapy seemed to be very promising, it has proven very modest results.<a class="elsevierStyleCrossRef" href="#bib0720">67</a></li><li class="elsevierStyleListItem" id="lsti0095">•mTOR inhibitors (mammalian target of rapamycin) – mTOR is a PI3K signaling pathway effector regulated by AKT and suppressor of PTEN tumors. PI3K pathway proteins are frequently affected by mutations in mammary carcinomas, and the loss of PTEN is a frequent discovery in TNBC; thus, increasing the activation of mTOR in the diseases.<a class="elsevierStyleCrossRef" href="#bib0725">68</a> It is for this reason that today, mTOR inhibitor drugs have been under evaluation.<a class="elsevierStyleCrossRef" href="#bib0730">69</a></li><li class="elsevierStyleListItem" id="lsti0100">•Bicalutamide/enzalutamide (“anti-androgen” targeted therapy): Some preclinical studies showed that luminal TNBC which expresses the androgen receptor (AR) is sensitive to androgen deprivation. Bicalutamide as monotherapy demonstrated a clinical benefit of 19% of the AR positive.<a class="elsevierStyleCrossRef" href="#bib0735">70</a> Today, a phase II study is evaluating enzalutamide's safety and efficacy in TNBC and AR positive patients. Results are yet to be seen.</li></ul>Targeted therapies against some identified biomarkers in TNBC have not proven a significant improvement, the problem has been the lack of dependable predictive biomarkers, which is essential before any of these treatments can be introduced in clinical practice.ConclusionsTNBC is usually the most aggressive type of cancer and it is linked to the highest mortality rate in comparison to other types of BC. Numerous advances in the understanding of this cancer have been made. Reported genomic signatures to date reflect the heterogeneity of the triple negative phenotype, at the same time have allowed for a TNBC classification into 6 clinically relevant subgroups. One of these subgroups has a strongly immune component. Another subgroup shares biological characteristics with mutations in genes BRCA1/2 with deficiency in DNA repair.While several TNBC biomarkers are reported in the literature every year, only few have exceeded validation to justify its use in clinical practice. The reason for this deterioration may be due to the fact that while strong associations often derive initially between the expression of a putative biomarker and the stage of the disease, candidate markers do not often have any relevant and significant functions of the disease in clinical laboratory and therapeutic practice. For TNBC specifically, different research groups that used the information generated by microarrays obtained results varying from one group to another and in some cases these results have not been able to be validated. This could be a result of the inherent heterogeneity of TNBC or each experiment design's own limitations, such as: (1) the use of large data base retrospective cohorts, where TNBC's classification is based solely on the information obtained from the gene expression profile data, this methodology is not the standard in clinical practice. Also, this information shows limitations due to how varying the data collection and sample management methods are used (in some cases paraffin-embedded tissue was utilized, others utilized fresh tissue, etc.) to feed the databases that are afterwards referenced by other researchers; (2) limited gene expression analysis of a determined number of genes, instead of conducting a global analysis of gene expression; (3) previous works and researches compared TNBC gene expression profiles vs other BC subtypes, or TNBC vs normal tissue, which does not unify stratification criteria.In Mexico, there are few research papers which report the analysis of TNBC expression profiles This is concerning, since this type of BC jeopardizes a considerable amount of cases among the Mexican population, hence it is necessary to increase efforts in the search of biomarkers or possible therapeutic targets which can be validated in our population.FundingCONACyT Fondo Salud162301 and Convocatoria de Becas Nacionales2014-370024.Conflict of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres719218" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec724449" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Breast cancer classification" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Prognostic value of genomic signatures in BC" ] 5 => array:3 [ "identificador" => "sec0020" "titulo" => "Triple negative breast cancer (TNBC)" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "TNBC risk factors" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Molecular classification of TNBC subtypes" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "The search for TNBC biomarkers" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "TNBC treatment" ] ] ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusions" ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-12-15" "fechaAceptado" => "2016-05-04" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec724449" "palabras" => array:3 [ 0 => "Triple negative breast cancer" 1 => "Gene expression" 2 => "Biomarkers" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Triple negative breast cancer (TNBC) is a subtype of breast cancer (BC) with a heterogeneous nature that stains negatively for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) during immunohistochemistry. Approximately 15–20% of all cases of breast cancer are triple negative phenotypes. Compared to patients with hormone receptor-positive cancer, TNBC patients are typically younger (<50 years), African American, and have a high incidence of mutations in BRCA1/2 genes. To date, not a single targeted therapy has been approved for TNBC treatment, and cytotoxic chemotherapy remains as the standard systemic treatment, meaning that TNBC is an aggressive subtype of breast cancer with a poor prognosis. In this review, the literature search was done up to date on which gene expression profile of TNBC has been analyzed in order to identify the consensus on molecular mechanisms involved in carcinogenesis and/or the prognostic markers of the disease. In conclusion, these studies have reported that TNBC is composed of several clusters or genomic signatures as basal keratins. They have also reported on their proliferation, luminal/basal apocrine, regulatory interferon, immune cells/immunoglobulin related to stem cells, epithelial-mesenchymal, androgen receptor and angiogenesis. However, not all research groups have reported reproducible results. This confirms the heterogeneous nature of TNBC and the need for research on uniform selection criteria. However, these discoveries have led to the proposal of new treatments, such as the addition of platinum salts, new combinations of therapeutic agents, some targeted therapies such as PARP inhibitors, and PI3K and androgen antagonists. There is no doubt that a better understanding of the nature of TNBC will allow individualized and more effective therapies." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1515 "Ancho" => 2646 "Tamanyo" => 214223 ] ] "descripcion" => array:1 [ "en" => "Breast cancer classification according to immunohistochemistry cellular markers (IHC) or according to a combination of IHC and microarray expression methods (gene signatures). ER, estrogen receptors; PR, progesterone receptors; HER2, epidermal growth receptor 2; CK, cytokeratin; EGFR, growth factor receptor." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1999 "Ancho" => 2833 "Tamanyo" => 649725 ] ] "descripcion" => array:1 [ "en" => "Breast cancer classification example using PAM50." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1400 "Ancho" => 2595 "Tamanyo" => 226783 ] ] "descripcion" => array:1 [ "en" => "Lehman's triple negative breast cancer classification, gene ontology and proportion. TNBC, triple negative breast cancer; BL1, basal like 1; BL2, basal like 2; IM, immunomodulatory; M, mesenchymal; MSL, mesenchymal stem cell-type; LAR, androgen luminal receptor; MET, mesenchymal epithelial transition." ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Author \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Observation \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Main genes \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Signature objective \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Experiment design</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sample characteristics \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Comparison \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rody, 2011<a class="elsevierStyleCrossRef" href="#bib0680">59</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 meta-genes: basal phenotype, androgen receptor signaling, diverse immune cells, stroma, Claudine CD24, blood cell markers and adipocytes, inflammation and angiogenesis (VEGF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">EPHB3, GABRP, AR, FOXA1, IgG, TCR, LCK, ITK, HLA-DR, -DM, -DP, -DQ, HLA-A, -B, -C, -E, -F, -G, OAS1, OAS2, OAS3, MX1, Decorin, Osteonectin, Fibronectin. COL5A1, CLDN3, CLDN4, CD24, ELF3, BUB1, CDC2, STK6, BIRC5, TOP2A, HBA1, HBA2, HBB, FABP4, PLIN, ADIPOQ, ADH1B, VEGF, adrenomedulina, ANGPTL4, IL-8, CXCL1, CXCL2, HOXA-4, -5, -7, -9, -10, -11, Histones H2A, H2B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prognosis/therapeutic target \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Public database \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">394 TNBC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Karn, 2011<a class="elsevierStyleCrossRef" href="#bib0740">71</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 signatures (26 main genes) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL8, SCD, AQP3, SERPINE1, LYPDC1, PGK1, SEC23A, SNAPC1, SNF7DC2, SORT1, SPOCK, SRPX2, STC1, STMN2, SYNCRIP, TAX1BP3, TBC1D22B, TGFB2, TGFBI, THBS1, TIAM1, TLE6, TNFAIP1, TNFRSF10B, TRIM23, TSGA10, TXNDC9, U2AF1L1, ULBP2, UQCRC1, VLDLR, VMD2, WFDC1, WWTR1, ZA20D1, ZP2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prognosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Public database \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">394 TNBC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cascione, 2013<a class="elsevierStyleCrossRef" href="#bib0745">72</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2× microRNA signatures and 4 gene subgroups \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">miR-16, 155, 125b, 374a and miR-16, 125b, 374a, 374b, 421, 655, 497 Molecular subgroup 1: SPP1, MMP9, MYB12, BIRC5, TOP2A, CDC2, CDKN2A. Molecular subgroup 2: BCL2, EGF, ERBB4, AR, ESR1, IL1A, FGFR2, WT1, MYC, FGF2, AKT1, CASP10. Molecular subgroup 3: MET, L1CAM, IGFBP3. Molecular subgroup 4: TIMP1, TIMP2, CDKN1A, CCND2, MAP3K8, CAV1, LAMB1, JUN, CEBPA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sub-classification/therapeutic target \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Paraffin-embedded tissue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TNBC vs Adjacent tissue and lymph node injuries \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Komatsu, 2013<a class="elsevierStyleCrossRef" href="#bib0750">73</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">322 unregulated genes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Main overexpressed genes: UBE2C, S100P, UCHL1, PTTG1, UBE2T, SIX1, PRC1, TOP2A, HORMAD1, FABP5, ATAD2. Main sub-expressed genes: PIP, DNAL11, WIF1, SCUBE2, TBC1D9, TFF3, ERBB4, GATA3, MLPH. LAMAB, LTBP2, LIFR, LRP2, MASP2, MATN2, MGP, NTN4, NRG1, PTHLH, PI15, PLAT, PDGFA, PTN, PIGR, PIP, SCGB1D1, SCGB1D2, SCGB3A1, SEMA3G, STC2, THSD4, TFF3. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Therapeutic target \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fresh tissue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TNBC vs epithelial ductal cells \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Al-Ejeh, 2014<a class="elsevierStyleCrossRef" href="#bib0755">74</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 genes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAPT, MYB, MELK, MCM10, CENPA, EXO1, TTK and KIF2C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prognosis/therapeutic target \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Meta-analysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CMTN vs CMnTN \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Khaled, 2015<a class="elsevierStyleCrossRef" href="#bib0760">75</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 gene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BCL11A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Therapeutic target \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Public data base \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CMTN vs CMnTN \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">He, 2015<a class="elsevierStyleCrossRef" href="#bib0765">76</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 genes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">DUSP1 and FOXA1. DUSP1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Therapeutic targets \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Public data base \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CMTN vs CMnTN \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pacheco-Velazquez, 2014<a class="elsevierStyleCrossRef" href="#bib0770">77</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 genes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HIF-1α+c-MYC+2OGDH+E-cadherina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prognosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fresh tissue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CMTN vs CMnTN vs Normal tissue \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1182389.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main genes reported from researches which analyze TNBC gene expression profiles. TNBC, triple negative breast cancer; nTNBC, non-triple negative breast cancer." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:77 [ 0 => array:3 [ "identificador" => "bib0390" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Breast cancer statistics, 2013" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. DeSantis" 1 => "Surveillance and Health Services Research ACSEAG" 2 => "J. Ma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3322/caac.21203" "Revista" => array:6 [ "tituloSerie" => "CA Cancer J Clin" "fecha" => "2015" "volumen" => "64" "paginaInicial" => "52" "paginaFinal" => "62" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24114568" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0395" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Fact Sheets by Cancer. 2015; <a id="intr0005" class="elsevierStyleInterRef" href="http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx">http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx</a>." ] ] ] 2 => array:3 [ "identificador" => "bib0400" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Mexico – INEGI – Estadasticas a proposito del Dia Mundial de la lucha contra el cancer de mama. 19 October 2016; <a id="intr0010" class="elsevierStyleInterRef" href="http://mx.noticiasol.com/inegi/estadsticas-a-propsito-del-da-mundial-de-la-lucha-contra-el-cncer-de-mama--19-de-octubre.html">http://mx.noticiasol.com/inegi/estadsticas-a-propsito-del-da-mundial-de-la-lucha-contra-el-cncer-de-mama--19-de-octubre.html</a>." ] ] ] 3 => array:3 [ "identificador" => "bib0405" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biomarkers in triple negative breast cancer: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B.S. Yadav" 1 => "P. Chanana" 2 => "S. Jhamb" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5306/wjco.v6.i6.252" "Revista" => array:6 [ "tituloSerie" => "World J Clin Oncol" "fecha" => "2015" "volumen" => "6" "paginaInicial" => "252" "paginaFinal" => "263" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26677438" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0410" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Goldhirsch" 1 => "E.P. Winer" 2 => "A.S. Coates" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/annonc/mdt303" "Revista" => array:6 [ "tituloSerie" => "Ann Oncol" "fecha" => "2013" "volumen" => "24" "paginaInicial" => "2206" "paginaFinal" => "2223" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23917950" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0415" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Issues and updates: evaluating estrogen receptor-α, progesterone receptor, and HER2 in breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.C. Allred" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/modpathol.2010.55" "Revista" => array:6 [ "tituloSerie" => "Mod Pathol" "fecha" => "2010" "volumen" => "23" "paginaInicial" => "s52" "paginaFinal" => "s59" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20436503" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0420" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Integrative investigation on breast cancer in ER, PR and HER2-defined subgroups using mRNA and miRNA expression profiling" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "X. Dai" 1 => "A. Chen" 2 => "Z. Bai" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/srep06566" "Revista" => array:5 [ "tituloSerie" => "Sci Rep" "fecha" => "2014" "volumen" => "4" "paginaInicial" => "6566" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25338681" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0425" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular portraits revealing the heterogeneity of breast tumor subtypes defined using immunohistochemistry markers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "X. Dai" 1 => "Y. Li" 2 => "Z. Bai" 3 => "X.Q. Tang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/srep14499" "Revista" => array:6 [ "tituloSerie" => "Sci Rep" "fecha" => "2015" "volumen" => "5" "paginaInicial" => "14499" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26404658" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0264410X15014371" "estado" => "S300" "issn" => "0264410X" ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0430" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Triple-negative breast cancer: advancements in characterization and treatment approach" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. Hurvitz" 1 => "M. Mead" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/GCO.0000000000000239" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Obstet Gynecol" "fecha" => "2016" "volumen" => "28" "paginaInicial" => "59" "paginaFinal" => "69" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26694831" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0435" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular portraits of human breast tumours" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C.M. Perou" 1 => "T. Sørlie" 2 => "M.B. Eisen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/35021093" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2000" "volumen" => "406" "paginaInicial" => "747" "paginaFinal" => "752" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10963602" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0440" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "T. Sorlie" 1 => "C.M. Perou" 2 => "R. Tibshirani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.191367098" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci U S A" "fecha" => "2001" "volumen" => "98" "paginaInicial" => "10869" "paginaFinal" => "10874" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11553815" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0445" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "E.A. Rakha" 1 => "T.C. Putti" 2 => "D.M. Abd El-Rehim" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/path.1916" "Revista" => array:6 [ "tituloSerie" => "J Pathol" "fecha" => "2006" "volumen" => "208" "paginaInicial" => "495" "paginaFinal" => "506" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16429394" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0450" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. van de Rijn" 1 => "C.M. Perou" 2 => "R. Tibshirani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0002-9440(10)64476-8" "Revista" => array:6 [ "tituloSerie" => "Am J Pathol" "fecha" => "2002" "volumen" => "161" "paginaInicial" => "1991" "paginaFinal" => "1996" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12466114" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0455" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F.M. Blows" 1 => "K.E. Driver" 2 => "M.K. Schmidt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pmed.1000279" "Revista" => array:5 [ "tituloSerie" => "PLoS Med" "fecha" => "2010" "volumen" => "7" "paginaInicial" => "e1000279" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20520800" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0460" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Correlation of ER, PR and HER-2/Neu with other prognostic factors in infiltrating ductal carcinoma of breast" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Siadati" 1 => "M. Sharbatdaran" 2 => "N. Nikbakhsh" 3 => "N. Ghaemian" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Iran J Pathol" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "221" "paginaFinal" => "226" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26351488" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0465" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Strategies for subtypes – dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Goldhirsch" 1 => "W.C. Wood" 2 => "A.S. Coates" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/annonc/mdr304" "Revista" => array:6 [ "tituloSerie" => "Ann Oncol" "fecha" => "2011" "volumen" => "22" "paginaInicial" => "1736" "paginaFinal" => "1747" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21709140" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0470" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A gene-expression signature as a predictor of survival in breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.J. van de Vijver" 1 => "Y.D. He" 2 => "L.J. van’t Veer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa021967" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2002" "volumen" => "347" "paginaInicial" => "1999" "paginaFinal" => "2009" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12490681" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0475" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gene expression profiling predicts clinical outcome of breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "L.J. van’t Veer" 1 => "H. Dai" 2 => "M.J. van de Vijver" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/415530a" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2002" "volumen" => "415" "paginaInicial" => "530" "paginaFinal" => "536" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11823860" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0480" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Paik" 1 => "S. Shak" 2 => "G. Tang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa041588" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2004" "volumen" => "351" "paginaInicial" => "2817" "paginaFinal" => "2826" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15591335" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0485" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Paik" 1 => "G. Tang" 2 => "S. Shak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2005.04.7985" "Revista" => array:7 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2006" "volumen" => "24" "paginaInicial" => "3726" "paginaFinal" => "3734" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16720680" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0264410X14000826" "estado" => "S300" "issn" => "0264410X" ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0490" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1–3 positive lymph nodes in an independent validation study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Mook" 1 => "M.K. Schmidt" 2 => "G. Viale" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10549-008-0130-2" "Revista" => array:6 [ "tituloSerie" => "Breast Cancer Res Treat" "fecha" => "2009" "volumen" => "116" "paginaInicial" => "295" "paginaFinal" => "302" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18661261" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0495" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C.A. Drukker" 1 => "J.M. Bueno-de-Mesquita" 2 => "V.P. Retel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ijc.28082" "Revista" => array:7 [ "tituloSerie" => "Int J Cancer" "fecha" => "2013" "volumen" => "133" "paginaInicial" => "929" "paginaFinal" => "936" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23371464" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S073510971600944X" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0500" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Knauer" 1 => "S. Mook" 2 => "E.J. Rutgers" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Breast Cancer Res Treat" "fecha" => "2010" "volumen" => "120" "paginaInicial" => "655" "paginaFinal" => "661" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0505" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Supervised risk predictor of breast cancer based on intrinsic subtypes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.S. Parker" 1 => "M. Mullins" 2 => "M.C. Cheang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2008.18.1370" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2009" "volumen" => "27" "paginaInicial" => "1160" "paginaFinal" => "1167" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19204204" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0510" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Martin" 1 => "A. Prat" 2 => "A. Rodriguez-Lescure" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10549-013-2416-2" "Revista" => array:6 [ "tituloSerie" => "Breast Cancer Res Treat" "fecha" => "2013" "volumen" => "138" "paginaInicial" => "457" "paginaFinal" => "466" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23423445" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0515" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Dowsett" 1 => "I. Sestak" 2 => "E. Lopez-Knowles" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2012.46.1558" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2013" "volumen" => "31" "paginaInicial" => "2783" "paginaFinal" => "2790" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23816962" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0520" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prognostic utility of the breast cancer index and comparison to Adjuvant! Online in a clinical case series of early breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R.C. Jankowitz" 1 => "K. Cooper" 2 => "M.G. Erlander" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/bcr3038" "Revista" => array:5 [ "tituloSerie" => "Breast Cancer Res" "fecha" => "2011" "volumen" => "13" "paginaInicial" => "R98" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21999244" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0525" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Filipits" 1 => "M. Rudas" 2 => "R. Jakesz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-11-0926" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2011" "volumen" => "17" "paginaInicial" => "6012" "paginaFinal" => "6020" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21807638" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0530" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. Cuzick" 1 => "M. Dowsett" 2 => "S. Pineda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2010.31.2835" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2011" "volumen" => "29" "paginaInicial" => "4273" "paginaFinal" => "4278" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21990413" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0535" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular classification and molecular forecasting of breast cancer: ready for clinical application?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.D. Brenton" 1 => "L.A. Carey" 2 => "A.A. Ahmed" 3 => "C. Caldas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2005.03.3845" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2005" "volumen" => "23" "paginaInicial" => "7350" "paginaFinal" => "7360" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16145060" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0540" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "W.D. Foulkes" 1 => "I.M. Stefansson" 2 => "P.O. Chappuis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Natl Cancer Inst" "fecha" => "2003" "volumen" => "95" "paginaInicial" => "1482" "paginaFinal" => "1485" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14519755" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0545" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California Cancer Registry" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K.R. Bauer" 1 => "M. Brown" 2 => "R.D. Cress" 3 => "C.A. Parise" 4 => "V. Caggiano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cncr.22618" "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "2007" "volumen" => "109" "paginaInicial" => "1721" "paginaFinal" => "1728" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17387718" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0550" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The prognostic importance of triple negative breast carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H. Mersin" 1 => "E. Yildirim" 2 => "U. Berberoglu" 3 => "K. Gulben" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.breast.2007.11.031" "Revista" => array:6 [ "tituloSerie" => "Breast" "fecha" => "2008" "volumen" => "17" "paginaInicial" => "341" "paginaFinal" => "346" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18450442" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0555" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.I. Phipps" 1 => "R.T. Chlebowski" 2 => "R. Prentice" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/jnci/djr030" "Revista" => array:6 [ "tituloSerie" => "J Natl Cancer Inst" "fecha" => "2011" "volumen" => "103" "paginaInicial" => "470" "paginaFinal" => "477" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21346227" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0560" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R.M. Tamimi" 1 => "G.A. Colditz" 2 => "A. Hazra" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10549-011-1702-0" "Revista" => array:7 [ "tituloSerie" => "Breast Cancer Res Treat" "fecha" => "2012" "volumen" => "131" "numero" => "1" "paginaInicial" => "159" "paginaFinal" => "167" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21830014" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0565" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.M. Gaudet" 1 => "M.F. Press" 2 => "R.W. Haile" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10549-011-1616-x" "Revista" => array:6 [ "tituloSerie" => "Breast Cancer Res Treat" "fecha" => "2011" "volumen" => "130" "paginaInicial" => "587" "paginaFinal" => "597" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21667121" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0570" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A case–control study of reproductive factors associated with subtypes of breast cancer in Northeast China" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Xing" 1 => "J. Li" 2 => "F. Jin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s12032-009-9308-7" "Revista" => array:6 [ "tituloSerie" => "Med Oncol" "fecha" => "2010" "volumen" => "27" "paginaInicial" => "926" "paginaFinal" => "931" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19771534" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0575" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.I. Phipps" 1 => "R.T. Chlebowski" 2 => "R. Prentice" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cancer Epidemiol Biomark Prev" "fecha" => "2011" "volumen" => "20" "paginaInicial" => "454" "paginaFinal" => "463" "itemHostRev" => array:3 [ "pii" => "S0140673611606879" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0580" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.L. Kwan" 1 => "L.H. Kushi" 2 => "E. Weltzien" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/bcr2261" "Revista" => array:5 [ "tituloSerie" => "Breast Cancer Res" "fecha" => "2009" "volumen" => "11" "paginaInicial" => "R31" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19463150" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0585" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metabolic syndrome, insulin resistance, and mammographic density in pre- and postmenopausal women" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "B.K. Kim" 1 => "Y. Chang" 2 => "J. Ahn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10549-015-3544-7" "Revista" => array:6 [ "tituloSerie" => "Breast Cancer Res Treat" "fecha" => "2015" "volumen" => "153" "paginaInicial" => "425" "paginaFinal" => "434" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26277917" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0590" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The association of metabolic syndrome with triple-negative breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B. Maiti" 1 => "M.N. Kundranda" 2 => "T.P. Spiro" 3 => "H.A. Daw" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10549-009-0591-y" "Revista" => array:6 [ "tituloSerie" => "Breast Cancer Res Treat" "fecha" => "2010" "volumen" => "121" "paginaInicial" => "479" "paginaFinal" => "483" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19851862" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0595" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metabolic syndrome and triple-negative breast cancer: a new paradigm" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.A. Davis" 1 => "V.G. Kaklamani" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Int J Breast Cancer" "fecha" => "2012" "volumen" => "2012" "paginaInicial" => "1" "paginaFinal" => "10" ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0600" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Insulin-like growth factor-dependent proliferation and survival of triple-negative breast cancer cells: implications for therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Z. Davison" 1 => "G.E. de Blacquiere" 2 => "B.R. Westley" 3 => "F.E. May" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Neoplasia" "fecha" => "2011" "volumen" => "13" "paginaInicial" => "504" "paginaFinal" => "515" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21677874" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0605" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Higher population-based incidence rates of triple-negative breast cancer among young African-American women: implications for breast cancer screening recommendations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.C. Amirikia" 1 => "P. Mills" 2 => "J. Bush" 3 => "L.A. Newman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cncr.25862" "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "2011" "volumen" => "117" "paginaInicial" => "2747" "paginaFinal" => "2753" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21656753" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0610" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Triple receptor-negative breast cancer: the effect of race on response to primary systemic treatment and survival outcomes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Dawood" 1 => "K. Broglio" 2 => "S.W. Kau" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2008.17.9952" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2009" "volumen" => "27" "paginaInicial" => "220" "paginaFinal" => "226" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19047281" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0615" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ethnicity and breast cancer: factors influencing differences in incidence and outcome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R.T. Chlebowski" 1 => "Z. Chen" 2 => "G.L. Anderson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/jnci/dji064" "Revista" => array:7 [ "tituloSerie" => "J Natl Cancer Inst" "fecha" => "2005" "volumen" => "97" "paginaInicial" => "439" "paginaFinal" => "448" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15770008" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0264410X15000304" "estado" => "S300" "issn" => "0264410X" ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0620" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Breast cancer classification according to immunohistochemistry markers: subtypes and association with clinicopathologic variables in a peruvian hospital database" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C.S. Vallejos" 1 => "H.L. Gomez" 2 => "W.R. Cruz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3816/CBC.2010.n.038" "Revista" => array:6 [ "tituloSerie" => "Clin Breast Cancer" "fecha" => "2010" "volumen" => "10" "paginaInicial" => "294" "paginaFinal" => "300" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20705562" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0625" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunohistochemical profile and clinical-pathological variables in breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.R. Cintra" 1 => "M.T. Teixeira" 2 => "R.W. Diniz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Assoc Med Bras" "fecha" => "2012" "volumen" => "58" "paginaInicial" => "178" "paginaFinal" => "187" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22569612" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0630" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "[Molecular classification of breast cancer patients obtained through the technique of chromogenic in situ hybridization (CISH)]" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Fernandez" 1 => "A. Reigosa" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Investig Clin" "fecha" => "2013" "volumen" => "54" "paginaInicial" => "406" "paginaFinal" => "416" ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0635" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis, and association with menopausal status, body mass index, and parity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F. Lara-Medina" 1 => "V. Perez-Sanchez" 2 => "D. Saavedra-Perez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cncr.25961" "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "2011" "volumen" => "117" "paginaInicial" => "3658" "paginaFinal" => "3669" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21387260" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0640" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is triple negative a prognostic factor in breast cancer?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. Nishimura" 1 => "N. Arima" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s12282-008-0042-3" "Revista" => array:6 [ "tituloSerie" => "Breast Cancer" "fecha" => "2008" "volumen" => "15" "paginaInicial" => "303" "paginaFinal" => "308" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18369692" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0645" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Triple-negative breast cancer: clinical features and patterns of recurrence" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R. Dent" 1 => "M. Trudeau" 2 => "K.I. Pritchard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-06-3045" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2007" "volumen" => "13" "paginaInicial" => "4429" "paginaFinal" => "4434" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17671126" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0650" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B.S. Abdulkarim" 1 => "J. Cuartero" 2 => "J. Hanson" 3 => "J. Deschenes" 4 => "D. Lesniak" 5 => "S. Sabri" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2010.33.4714" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2011" "volumen" => "29" "paginaInicial" => "2852" "paginaFinal" => "2858" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21670451" "web" => "Medline" ] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0655" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "P.L. Nguyen" 1 => "A.G. Taghian" 2 => "M.S. Katz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2007.14.4287" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2008" "volumen" => "26" "paginaInicial" => "2373" "paginaFinal" => "2378" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18413639" "web" => "Medline" ] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0660" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "H. Masuda" 1 => "K.A. Baggerly" 2 => "Y. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-13-0799" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "5533" "paginaFinal" => "5540" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23948975" "web" => "Medline" ] ] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0665" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "G. von Minckwitz" 1 => "M. Untch" 2 => "J.U. Blohmer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2011.38.8595" "Revista" => array:7 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2012" "volumen" => "30" "paginaInicial" => "1796" "paginaFinal" => "1804" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22508812" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0264410X15000353" "estado" => "S300" "issn" => "0264410X" ] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0670" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. Liedtke" 1 => "C. Mazouni" 2 => "K.R. Hess" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2007.14.4147" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2008" "volumen" => "26" "paginaInicial" => "1275" "paginaFinal" => "1281" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18250347" "web" => "Medline" ] ] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0675" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "B. Kreike" 1 => "M. van Kouwenhove" 2 => "H. Horlings" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/bcr1771" "Revista" => array:5 [ "tituloSerie" => "Breast Cancer Res" "fecha" => "2007" "volumen" => "9" "paginaInicial" => "R65" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17910759" "web" => "Medline" ] ] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0680" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A clinically relevant gene signature in triple negative and basal-like breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Rody" 1 => "T. Karn" 2 => "C. Liedtke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/bcr3035" "Revista" => array:6 [ "tituloSerie" => "Breast Cancer Res" "fecha" => "2011" "volumen" => "13" "paginaInicial" => "R97" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21978456" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0264410X14017216" "estado" => "S300" "issn" => "0264410X" ] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0685" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "B.D. Lehmann" 1 => "J.A. Bauer" 2 => "X. Chen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI45014" "Revista" => array:6 [ "tituloSerie" => "J Clin Investig" "fecha" => "2011" "volumen" => "121" "paginaInicial" => "2750" "paginaFinal" => "2767" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21633166" "web" => "Medline" ] ] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0690" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.D. Burstein" 1 => "A. Tsimelzon" 2 => "G.M. Poage" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-14-0432" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2015" "volumen" => "21" "paginaInicial" => "1688" "paginaFinal" => "1698" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25208879" "web" => "Medline" ] ] ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0695" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "L.A. Carey" 1 => "E.C. Dees" 2 => "L. Sawyer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-06-1109" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2007" "volumen" => "13" "paginaInicial" => "2329" "paginaFinal" => "2334" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17438091" "web" => "Medline" ] ] ] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0700" "etiqueta" => "63" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Higher locoregional recurrence rate for triple-negative breast cancer following neoadjuvant chemotherapy, surgery and radiotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. Zhang" 1 => "S. Wang" 2 => "H.P. Israel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s40064-015-1116-2" "Revista" => array:5 [ "tituloSerie" => "SpringerPlus" "fecha" => "2015" "volumen" => "4" "paginaInicial" => "386" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26240784" "web" => "Medline" ] ] ] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0705" "etiqueta" => "64" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Targeted approaches to triple-negative breast cancer: current practice and future directions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Brunello" 1 => "L. Borgato" 2 => "U. Basso" 3 => "F. Lumachi" 4 => "V. Zagonel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Curr Med Chem" "fecha" => "2013" "volumen" => "20" "paginaInicial" => "605" "paginaFinal" => "612" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23278396" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0264410X14016934" "estado" => "S300" "issn" => "0264410X" ] ] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0710" "etiqueta" => "65" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changing end points in breast-cancer drug approval – the Avastin story" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.B. D’Agostino Sr." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMp1106984" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2011" "volumen" => "365" "paginaInicial" => "e2" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21707384" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109713060282" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0715" "etiqueta" => "66" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The PARP inhibitor AZD2281 (Olaparib) induces autophagy/mitophagy in BRCA1 and BRCA2 mutant breast cancer cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B. Arun" 1 => "U. Akar" 2 => "A.M. Gutierrez-Barrera" 3 => "G.N. Hortobagyi" 4 => "B. Ozpolat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3892/ijo.2015.3003" "Revista" => array:6 [ "tituloSerie" => "Int J Oncol" "fecha" => "2015" "volumen" => "47" "paginaInicial" => "262" "paginaFinal" => "268" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25975349" "web" => "Medline" ] ] ] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0720" "etiqueta" => "67" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "L.A. Carey" 1 => "H.S. Rugo" 2 => "P.K. Marcom" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2010.34.5579" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2012" "volumen" => "30" "paginaInicial" => "2615" "paginaFinal" => "2623" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22665533" "web" => "Medline" ] ] ] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0725" "etiqueta" => "68" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "L.H. Saal" 1 => "K. Holm" 2 => "M. Maurer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/0008-5472-CAN-04-3913" "Revista" => array:6 [ "tituloSerie" => "Cancer Res" "fecha" => "2005" "volumen" => "65" "paginaInicial" => "2554" "paginaFinal" => "2559" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15805248" "web" => "Medline" ] ] ] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0730" "etiqueta" => "69" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S.L. Ellard" 1 => "M. Clemons" 2 => "K.A. Gelmon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2008.21.3033" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2009" "volumen" => "27" "paginaInicial" => "4536" "paginaFinal" => "4541" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19687332" "web" => "Medline" ] ] ] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0735" "etiqueta" => "70" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Gucalp" 1 => "S. Tolaney" 2 => "S.J. Isakoff" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-12-3327" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "5505" "paginaFinal" => "5512" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23965901" "web" => "Medline" ] ] ] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0740" "etiqueta" => "71" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Homogeneous datasets of triple negative breast cancers enable the identification of novel prognostic and predictive signatures" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "T. Karn" 1 => "L. Pusztai" 2 => "U. Holtrich" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0028403" "Revista" => array:5 [ "tituloSerie" => "PLoS ONE" "fecha" => "2011" "volumen" => "6" "paginaInicial" => "e28403" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22220191" "web" => "Medline" ] ] ] ] ] ] ] ] 71 => array:3 [ "identificador" => "bib0745" "etiqueta" => "72" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Integrated microRNA and mRNA signatures associated with survival in triple negative breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "L. Cascione" 1 => "P. Gasparini" 2 => "F. Lovat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0055910" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "e55910" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23405235" "web" => "Medline" ] ] ] ] ] ] ] ] 72 => array:3 [ "identificador" => "bib0750" "etiqueta" => "73" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Komatsu" 1 => "T. Yoshimaru" 2 => "T. Matsuo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3892/ijo.2012.1744" "Revista" => array:6 [ "tituloSerie" => "Int J Oncol" "fecha" => "2013" "volumen" => "42" "paginaInicial" => "478" "paginaFinal" => "506" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23254957" "web" => "Medline" ] ] ] ] ] ] ] ] 73 => array:3 [ "identificador" => "bib0755" "etiqueta" => "74" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Meta-analysis of the global gene expression profile of triple-negative breast cancer identifies genes for the prognostication and treatment of aggressive breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F. Al-Ejeh" 1 => "P.T. Simpson" 2 => "J.M. Sanus" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/oncsis.2014.14" "Revista" => array:5 [ "tituloSerie" => "Oncogenesis" "fecha" => "2014" "volumen" => "3" "paginaInicial" => "E100" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24752235" "web" => "Medline" ] ] ] ] ] ] ] ] 74 => array:3 [ "identificador" => "bib0760" "etiqueta" => "75" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "W.T. Khaled" 1 => "S. Choon Lee" 2 => "J. Stingl" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ncomms6987" "Revista" => array:6 [ "tituloSerie" => "Nat Commun" "fecha" => "2015" "volumen" => "6" "paginaInicial" => "5987" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25574598" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0264410X08017623" "estado" => "S300" "issn" => "0264410X" ] ] ] ] ] ] ] 75 => array:3 [ "identificador" => "bib0765" "etiqueta" => "76" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular features of triple negative breast cancer: microarray evidence and further integrated analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. He" 1 => "J. Yang" 2 => "W. Chen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0129842" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "e0129842" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26103053" "web" => "Medline" ] ] ] ] ] ] ] ] 76 => array:3 [ "identificador" => "bib0770" "etiqueta" => "77" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of a metabolic and canonical biomarker signature in Mexican HR+/HER2−, triple positive and triple-negative breast cancer patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S.C. Pacheco-Velazquez" 1 => "J.C. Gallardo-Perez" 2 => "J.L. 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Review article

G.I. Uscanga-Peralesa, S.K. Santuario-Faciob, R. Ortiz-Lópeza,b,

Corresponding author

rortizlopez@gmail.com

Corresponding author at: Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Av. Francisco I. Madero y Dr. Eduardo Aguirre Pequeño, s/n Col. Mitras Centro, Monterrey, N.L. C.P. 64460, Mexico. Tel.: +52 81 83485287; fax: +52 81 83337747.

a Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico

b Unidad de Genómica, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León, Monterrey, Mexico

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annually&#46; However&#44; in emerging countries this increase is up to 5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Despite having the same origin tissue&#44; BC represents a heterogeneous cancer group with complex biological behavior and a great clinical variability&#46; Over the last 10 years&#44; extensive research at a molecular and genetic level has been conducted in order to sub-type these BCs&#46; This has permitted the determination of clinical&#44; pathological and molecular variables&#44; to select treatment modalities and forecast&#44; in some cases&#44; the evolution of the disease at the moment of diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Breast cancer classification</span><p id="par0015" class="elsevierStylePara elsevierViewall">In the traditional way the most important information that pathologists gave oncologists&#44; respect to the classification of breast cancer&#44; included the status of the nodules and tumor size&#44; histological grade and standard immunohistochemistry tests &#40;IHC&#41; status of hormone receptors&#58; estrogen receptor &#40;ER&#41; and progesterone receptor &#40;PR&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Later on&#44; in the era of trastuzumab&#44; information on the amplification status of the human epidermal growth factor receptor 2 gene &#40;HER2&#41; became routine&#46; Combining all these parameters&#44; it was possible to classify patients as high or low risk&#46; There were however a group of patients who were in an intermediate category that could not be classified between these two groups&#46; Results showed that 15&#37; of the patients classified as low risk had relapsed or died due to a very aggressive disease&#46; And patients classified as high risk&#44; surprisingly 10&#8211;15&#37; had a favorable response&#46; All those results led to the conclusion that the method of classification was not very appropriate&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Thus&#44; based only on standard IHC directed at cellular markers that reflect the availability of targeted therapies&#44; breast cancer can also be classified into three main groups&#58; &#40;a&#41; homone sensitive &#40;ER or PR positive&#41;&#44; &#40;b&#41; HER2 positive&#44; sensitive to trastuzumab or &#40;c&#41; triple negative breast cancer &#40;TNBC&#41;&#44; defined by the absence of ER&#44; PR and HER2 amplification&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">5&#8211;8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">No targeted treatment is available for TNBT and chemotherapy remains the best therapeutic option&#46; However&#44; in the case of recurrence or chemoresistance&#44; 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negative or low positive PR&#59; &#40;c&#41; positive for HER2 &#8211; overexpressed or amplified HER2&#44; negative ER and PR&#59; &#40;d&#41; basal-like or TNBC&#44; also defined by the absence of ER&#44; PR and HER2 amplification&#46; However&#44; this last assumption is not strictly accurate due as not all basal-like tumors are completely TNBC&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">This classification is based on the consideration that there are two cell types in the mammary gland&#44; luminal cells and basal cells&#46; These two cell types can be differentiated by IHC tests as luminal cells&#44; which express ER and PR and that are positive for keratins 8&#47;18&#44; while basal cells are positive for keratins 5&#47;6 and 17&#46;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Because of the cost involved in utilizing microarray technology in the clinic&#44; the most employed technique for BC classification remains IHC and FISH&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">6&#44;8&#44;14</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Between 60&#37; and 70&#37; of all breast cancers correspond to positive ER and PR subtypes&#44;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">6</span></a> which usually respond to targeted ER therapy&#44; such as selective ER modulators &#40;i&#46;e&#46; tamoxifen&#44; or aromatase inhibitors&#41; which reduce serum estrogen concentrations&#46; Around 15&#8211;20&#37; of BCs amplify or overexpress the HER2 oncogene&#46; This type of cancer is associated with an incorrect prognosis and the treatments specifically aimed at HER2 &#40;i&#46;e&#46; trastuzumab&#41; have greatly improved results in women with BC HER2&#43;&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Prognostic value of genomic signatures in BC</span><p id="par0055" class="elsevierStylePara elsevierViewall">Despite the fact that they have not completely turned into routine methods&#44; genomic methods have been used in research studies with the purpose of&#58; &#40;a&#41; getting a better understanding of the nature of these variations of BC&#59; &#40;b&#41; stratifying patients through assessment of the evolution of the disease &#40;evaluating clinical pathological characteristics&#41;&#44; and &#40;c&#41; understanding the possible response of the patient to treatment &#40;in relationship with ER&#44; PR&#44; HER2 and the proliferation rate&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">5&#44;16</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Through global expression analysis with microarrays&#44; the identification of gene groups &#40;genomic signatures&#41; has been possible&#44; which allow us to estimate risk of recurrence of the disease and&#47;or predict the response to adjuvant therapy in BC patients in the early stages&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">17&#8211;20</span></a> Some of these genomic signatures have been validated in large cohorts and have been the precedent for some commercial genomic tests&#44; providing complementary information to clinicians in order to obtain a more precisely classification patients who has a high risk of recurrence&#44; and to offer more personalized attention&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The first commercial signature&#44; and the one still widely distributed under its commercial name&#44; is MammaPrint<span class="elsevierStyleSup">&#174;</span> &#40;Agilent&#44; Amsterdam&#44; Holland&#41;&#46; This signature measures mRNA of 70 gene expression and was approved by the US FDA and by regulators in the EU as an essay with prognostic value in patients with BC who are under 61 years of age&#44; in an I&#47;II stage&#44; with negative lymph nodes or one to three positive lymph nodes&#46; In addition to accurately identifying patients who can safely avoid adjuvant chemotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">17&#44;21</span></a> MammaPrint stratifies patients into low-risk or high-risk groups&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">17</span></a> However&#44; even though discrimination is good for ER&#43; cancers&#44; it is not the same with ER&#8722; cancers&#44;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">22&#44;23</span></a> limiting its clinical value to a subgroup of patients&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Another widely distributed and commercially available assay is Oncotype DX<span class="elsevierStyleSup">&#174;</span> test &#40;Genomic Health&#44; Redwood City&#44; CA&#44; U&#46;S&#46;&#41;&#46; This test is used to classify patients with Luminal A and B BCs&#44; as well as HER2&#43; subtypes &#40;though not TNBC&#41;&#44; since it has been designed to assess genes related to ER&#44; proliferation genes&#44; HER2 genes&#44; and genes related to invasion&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">19</span></a> This test allows the oncologist to discern whether or not chemotherapy treatment will be beneficial&#46; This essay measures the 21-gene expression&#44; which provides information of the recurrence of the disease through a scoring system from 0 to 100&#44; stratifying patients into low-risk &#40;score &#60;18&#41;&#44; intermediate risk &#40;score 18&#8211;30&#41; or high risk &#40;&#8805;31&#41; groups&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">19&#44;20</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">A third test&#44; consisting of an algorithm for the intrinsic molecular classification of BC&#44; has been nominated PAM50 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; This was designed to improve IHC and microarray classification aggreance&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">24</span></a> This 50-gene signature can classify BCs as luminal A&#44; luminal B&#44; HER2 and basal-like&#46; The PAM50 score was designed with the purpose of translating the different intrinsic subtypes into an associated prognostic value&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">24</span></a> An application of this score is the identification of patients who may benefit from the weekly addition of paclitaxel to conventional chemotherapy with anthracycline as an adjuvant treatment of operable BC with positive lymph nodes&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">25</span></a> In 2013&#44; Prosigna &#40;Seattle&#44; Washington&#44; U&#46;S&#46;&#41; started commercializing a diagnostic kit which qualifies mRNA expression of the 50 genes used by the algorithm in order to calculate the risk of recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">26</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">In addition to these tests&#44; which are the most commonly distributed&#44; there are others in the market&#44;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">27&#8211;29</span></a> where the common denominator is the measurement of gene expression of proliferation related genes&#46; It is important to mention that these multiple-gene assays are for the most part&#44; if not exclusively&#44; applicable to luminal BC&#44; thus stressing once more the need to search for and identify markers with prognostic value and response to treatment in BC patients with negative hormonal receptors or HER2 amplification&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Triple negative breast cancer &#40;TNBC&#41;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Since 1997&#44; the National Comprehensive Cancer Network &#40;NCCN&#41; has gathered data of women with newly diagnosed breast cancer&#44; representing many institutions around the U&#46;S&#46; HER2 by IHC&#39;s status was added to the data from the NCCN as a routine element in the year 1999&#44; and HER2 status through fluorescent in situ hybridization &#40;FISH&#41; was added in 2001&#46; The term &#8220;Triple Negative Breast Cancer&#8221; &#40;TNBC&#41; appeared for the first time in the literature in 2005&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">30</span></a> Due to the lack of effective therapeutic options&#44; many studies have focused on the understanding of the biology of TNBC for the selection of biomarkers and therapeutic targets&#46; In this review&#44; we will focus on making a compilation of molecular and gene studies in reference to this BC subgroup&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">TNBC risk factors</span><p id="par0090" class="elsevierStylePara elsevierViewall">TNBC makes up about 15&#8211;20&#37; of all BCs and follows an aggressive clinical course&#44; including a high incidence of visceral and nervous metastases&#44; compared to BCs positive to hormone receptors&#44; TNBC is more frequently associated with BRCA1 and&#44; to a lesser extent&#44; BRCA2 mutations&#46;<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">31&#44;32</span></a> It has also been associated with a high local recurrence rate at three years after treatment&#44; and a high death rate at 5 years&#46; Upon long-range metastasis&#44; the survival rate is poor&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">33</span></a> Differently from other subtypes of BC &#40;Luminal A&#44; B and HER2&#41;&#44; where early pregnancy has been recognized as a protective factor against BC&#44; gestation appears to be an important risk factor in the development of the triple negative phenotype&#46; In a study by Phipps et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">34</span></a> they reported that women who had more children &#40;three or more&#41; had a greater risk &#40;1&#46;4 times&#41; of TNBC&#46; Later&#44; a study by Tamimi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">35</span></a> reaffirmed that multiple pregnancies were associated with an increased risk of developing TNBC&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Other behaviors associated with the triple negative subtype are a lack of lactation&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">36</span></a> and various studies have made an association between TNBC and a high body mass index &#40;BMI&#41;&#44; a metabolic syndrome&#44; type 2 diabetes&#44; obesity and&#47;or insulin resistance&#46;<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">37&#8211;43</span></a> Consequently&#44; patients with TNBC are the group with the worst prognosis&#44; which is important to consider in a country like Mexico&#44; which has an elevated prevalence of obesity and metabolic syndrome&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Racial ancestry has been shown to have an important relation to TNBC&#44; since 21&#37; of Afro American BCs have been classified as TNBC &#40;compared to 15&#37; of the Caucasian population&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">44&#8211;46</span></a> The Hispanic population has also shown a high incidence of this cancer subtype&#44; with a frequency of 21&#46;3&#37; in Peru&#44;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">47</span></a> 27&#37; in Brasil&#44;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">48</span></a> 24&#46;1&#37; in Venezuela<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">49</span></a> and 23&#46;1&#37; in Mexico&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">50</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">TNBC presents a high rate of proliferation<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">51</span></a> and is highly aggressive&#46;<a class="elsevierStyleCrossRefs" href="#bib0545"><span class="elsevierStyleSup">32&#44;52&#8211;54</span></a> In a study by Sorlie et al&#46;&#44; in which the response to an uniform treatment was evaluated&#44; they reported differing results between patients belonging to groups of distinct subtypes&#46; Among these results exist a report that patients with TNBC had the worst prognosis by a significant margin when compared to patients with cancers that had positive hormone receptors&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">11</span></a> In a later study&#44; Dent et al&#46; compared the clinical history&#44; outcome and the nature of the disease in women with TNBC to women with other subtypes&#46; The results showed that TNBC had a low survival rate and a high rate of long-distance metastasis after treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">52</span></a> Due to TNBC&#39;s aggressive course&#44; these types of cancers can be highly sensitive to cytotoxic medications&#46; The proportion of patients who reach a complete pathological response &#40;CPR&#41; after treatment were found to be 30&#8211;45&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0660"><span class="elsevierStyleSup">55&#44;56</span></a> and the patients&#44; which achieved a CPR had excellent long-term results&#44; with a global survival rate higher than 90&#37;&#46; In addition&#44; if CPR is achieved&#44; patients with TNBC or other types of BC had a similar survival rate&#46; However&#44; those patients with TNBC who presented with a residual disease had worse results than patients with other types of BC&#46;<a class="elsevierStyleCrossRefs" href="#bib0610"><span class="elsevierStyleSup">45&#44;57</span></a> The aggressiveness of TNBC and the shortage of specific therapeutic options underline the need to understand the ways in which this type of cancer develops&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Molecular classification of TNBC subtypes</span><p id="par0110" class="elsevierStylePara elsevierViewall">In 2007&#44; Kreike et al&#46; reported that TNBCs were synonymous with basal type molecular cancers&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">58</span></a> However&#44; as we mentioned before&#44; it has been proven that TNBC&#39;s molecular biology is diverse and heterogenous&#44;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">59</span></a> and that TNBC is not an ideal substitute for the basal phenotype&#46; In 2011&#44; Lehmann et al&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">60</span></a> identified 6 subtypes of TNBC&#44; as well as 1 unstable subtype&#46; The six subtypes included two basal like &#40;BL1 and BL2&#41;&#44; one immunomodulatory class&#44; one mesenchymal class&#44; one mesenchymal stem cell &#40;MSC&#41; class&#44; and one luminal androgen receptor &#40;LAR&#41; class&#46; In addition&#44; gene expression analysis allowed the authors to identify the cell lines representative of each TNBC subtype to later evaluate their response to different medications&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">BLI&#58;</span> Cancers in this group are characterized by their rapid cell division&#44; with an increased proliferation rate and loss of cell cycle control&#46; Due to this&#44; they present an elevated expression &#40;mRNA&#41; of Ki67 and respond to antimitotic agents&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><p id="par0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">BL2&#58;</span> These cancers present the expression of EGFR&#44; TP63&#44; MET&#44; etc&#46; and involve activation of glycolysis and gluconeogenesis routes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><p id="par0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">IM&#58;</span> They are composed of response cells from the immune system&#44; and present antigens and cytokine expression&#46; They overlap with medullary breast cancer with a favorable prognosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">M and MSL&#58;</span> These groups present epithelial-mesenchymal transition markers&#44; including angiogenesis &#40;VEGFR2&#41; and most likely respond to desatinib &#40;TK inhibitors&#41; and mTOR&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">LAR&#58;</span> This group is characterized by the expression of androgen receptors &#40;AR&#41;&#46; They are RE negative&#44; but maintain an elevated hormonal component&#44; regulated by steroid synthesis&#44; porphyrin metabolism genes and androgens&#47;estrogens&#46; The AR&#39;s expression is up to nine times more than the other groups&#44; and are prime candidates for anti-androgen therapies&#46;</p></li></ul></p><p id="par0140" class="elsevierStylePara elsevierViewall">The signaling pathways obtained by the study are potential pharmacological targets in these cell models to that analysis of these distinct genetic signatures can be used to select a therapy&#46; In general&#44; it was observed that the BL1 and BL2 subtypes respond well to cisplatin&#44; and that the M and MSL types respond well to NVP-BEZ235&#44; a PI3K&#47;mTOR inhibitor and dasatinib &#40;a tyrosine kinase inhibitor&#41;&#46; The LAR subtype was only sensitive to bicalutamide &#40;an androgen receptor agonist&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Later&#44; Burstein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">61</span></a> confirmed four of the subtypes reported by Lehmann with the base DNA profiles or the single nucleotide DNA markers from 198 TNBC samples&#58; one luminal androgen receptor type&#44; one mesenchymal type&#44; and two basal types&#46; These studies by Burstein and Lehmann suggested the existence of at least 4 TNBC subtypes &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">The search for TNBC biomarkers</span><p id="par0150" class="elsevierStylePara elsevierViewall">Various expression studies have been performed on TNBC with the aim of identifying therapeutic targets&#44; which have been summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; This summary includes the characteristics of each study and the selected differentially expressed principal genes&#46; This table shows the variability of the data obtained from each study&#46; This indicates that validation of these possible molecular targets is necessary and even more studies are required to find efficient biomarkers for the treatment of TNBC&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">TNBC is a subtype of BC with a very heterogeneous behavior which&#44; based on gene expression analysis by microarray&#44; was classified by Lehmann into six distinct groups&#46; This sub-classification is not only useful to the better understanding of this disease&#44; but also to identify new molecular targets for its treatment&#46; Following are some of the proteins which have been identified in these TNBC groups as potential therapeutic targets&#46;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030"><p id="par0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">EGFR&#58;</span> This is one of the principal receptors&#44; and plays an important role in the survival of the tumor&#46; It is a marker of cellular proliferation&#44; angiogenesis&#44; metastasis and apoptosis inhibition&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><p id="par0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">VEGF&#58;</span> This is the principal marker for angiogenesis&#46; It induces proliferation and maintains the integrity of the cell&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><p id="par0170" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">C-kit and basal cytokeratins&#58;</span> C-kit unites with the receptor of a growth factor&#44; stimulates survival and differentiation&#44; and induces invasiveness in the cancerous cell&#46; The basal cytokeratins are intermediate filament proteins&#46; Their expression is constant when epithelium undergoes transformation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><p id="par0175" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">P53&#58;</span> suppressor protein important in cell cycle regulation and tumor apoptosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><p id="par0180" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">hKi67&#58;</span> A cellular proliferation marker which is present in the nucleus during interphase and mitosis&#46; Ki67 expression in normal mammary tissue is &#60;3&#37;&#46; The expression of TNBC can elevate it up to 80&#37;&#46; It self-expresses particularly in RE-negative cells&#46; It is associated with an unfavorable prognosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><p id="par0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">PARP&#58;</span> A family of cell signaling enzymes&#46; 18 PARP proteins have been identified&#46; PARP1 is responsible for the majority of its functions&#46; It is a DNA damage sensor and plays an important role in its repair and in responses to inflammation&#44; ischemia and oxidative stress&#46; In cells with a BRCA mutation&#44; PARP inhibition contributes to cell death by apoptosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Hsp90&#58;</span> A cellular chaperone&#44; it stabilizes the conformation of many labile proteins&#44; such as steroid receptors&#44; CDK4&#44; RAF-1 and AKT&#44; etc&#46; PU-H71 is a cyclin inhibitor which has been shown to be useful in some TNBC models&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">COX2&#58;</span> This protein is expressed by the inflammatory stimulus and its expression is associated with an unfavorable prognosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><p id="par0200" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">TK&#58;</span> A regulatory protein which helps the cell grow and differentiate itself&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><p id="par0205" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">mTOR&#58;</span> The over-expression of these proteins &#40;PI3K&#47;mTOR&#41; is associated with a poor response to treatment with hormones and trastuzumab&#46;</p></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">TNBC treatment</span><p id="par0210" class="elsevierStylePara elsevierViewall">Women with TNBC are not able to take endocrinology therapies neither HER2 targeted therapies&#44; hence treatment options are limited to surgery&#44; radiotherapy and chemotherapy&#44;<a class="elsevierStyleCrossRefs" href="#bib0695"><span class="elsevierStyleSup">62&#44;63</span></a> being chemotherapy the standard treatment of TNBC&#46; In the past two decades the use of more aggressive therapy has produced a clearer improvement in quality of life&#59; however&#44; there is a consensus opinion&#44; which considers that it would be impossible to improve these results if this cytotoxic therapy remained the only option to be offered to these patients&#46; For this reason&#44; there is an urge to find new &#8220;intelligent drugs&#8221; capable of solving chemoresistance and reducing the risks of chemotherapy in patients who do respond&#46; The greatest obstacle to find actionable targets is the vast heterogeneity both inter and intra-tumor of the TNBC&#46; In fact&#44; several years of study have failed to prove a unified alteration which may serve as targets of a targeted therapy&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Several researches about TNBC describe genomic signatures involving affected signaling pathways&#44; including cellular&#44; immunologic and metabolic processes like &#8211; basal keratin differential expressions&#44; interferon proliferation and regulation routes&#44; low expression in Claudine&#44; mesenchymal epithelial transition&#44; androgen receptor expression &#40;AR&#41; and angiogenesis activation &#40;VEGF&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0675"><span class="elsevierStyleSup">58&#8211;60</span></a> These findings have revealed potential molecular targets&#44;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">49</span></a> and different drug types are currently found under investigation&#44; which can basically be defined in four groups&#58; &#40;1&#41; agents which cause damage to DNA &#40;i&#46;e&#46; cisplatin&#44; cyclophosphamide&#41;&#44; &#40;2&#41; agents which inhibit poly &#40;ADP-ribose&#41; polymerase &#40;PARP inhibitors&#41;&#44; &#40;3&#41; tyrosine-kinase inhibitors and &#40;4&#41; agents which inhibit downstream signaling pathways &#40;mainly PI3K&#47;AKT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">64</span></a> Down below there are the descriptions of treatments which have been proven depending upon identified therapeutic targets in TNBC&#46;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0220" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Bevacizumab&#58;</span> Anti-VEGF &#40;vascular endothelial growth factor&#41; monoclonal antibody that blocks angiogenesis&#59; although&#44; a lack of efficiency as well as a toxicity increment have been observed&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">65</span></a></p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8226;</span><p id="par0225" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Olaparib&#47;iniparib&#58;</span> PARP inhibitors in patients with mutations in BRCA1&#47;2&#44; they have also been widely studied since they have shown to have anticancer selective activity in BRCA1 and BRCA2-deficient cancers&#59; nevertheless&#44; the relevance of the inhibition of these enzymes has yet to be confirmed&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">66</span></a></p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8226;</span><p id="par0230" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Cetuximab&#58;</span> Anti-EGFR monoclonal targeted antibody&#44; it has been evaluated as monotherapy or with a platinum-based therapy &#40;carboplatin&#41;&#46; Even though&#44; at first&#44; this therapy seemed to be very promising&#44; it has proven very modest results&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">67</span></a></p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8226;</span><p id="par0235" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">mTOR inhibitors</span> &#40;mammalian target of rapamycin&#41; &#8211; mTOR is a PI3K signaling pathway effector regulated by AKT and suppressor of PTEN tumors&#46; PI3K pathway proteins are frequently affected by mutations in mammary carcinomas&#44; and the loss of PTEN is a frequent discovery in TNBC&#59; thus&#44; increasing the activation of mTOR in the diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">68</span></a> It is for this reason that today&#44; mTOR inhibitor drugs have been under evaluation&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">69</span></a></p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8226;</span><p id="par0240" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Bicalutamide&#47;enzalutamide</span> &#40;&#8220;anti-androgen&#8221; targeted therapy&#41;&#58; Some preclinical studies showed that luminal TNBC which expresses the androgen receptor &#40;AR&#41; is sensitive to androgen deprivation&#46; Bicalutamide as monotherapy demonstrated a clinical benefit of 19&#37; of the AR positive&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">70</span></a> Today&#44; a phase II study is evaluating enzalutamide&#39;s safety and efficacy in TNBC and AR positive patients&#46; Results are yet to be seen&#46;</p></li></ul></p><p id="par0245" class="elsevierStylePara elsevierViewall">Targeted therapies against some identified biomarkers in TNBC have not proven a significant improvement&#44; the problem has been the lack of dependable predictive biomarkers&#44; which is essential before any of these treatments can be introduced in clinical practice&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="par0250" class="elsevierStylePara elsevierViewall">TNBC is usually the most aggressive type of cancer and it is linked to the highest mortality rate in comparison to other types of BC&#46; Numerous advances in the understanding of this cancer have been made&#46; Reported genomic signatures to date reflect the heterogeneity of the triple negative phenotype&#44; at the same time have allowed for a TNBC classification into 6 clinically relevant subgroups&#46; One of these subgroups has a strongly immune component&#46; Another subgroup shares biological characteristics with mutations in genes BRCA1&#47;2 with deficiency in DNA repair&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">While several TNBC biomarkers are reported in the literature every year&#44; only few have exceeded validation to justify its use in clinical practice&#46; The reason for this deterioration may be due to the fact that while strong associations often derive initially between the expression of a putative biomarker and the stage of the disease&#44; candidate markers do not often have any relevant and significant functions of the disease in clinical laboratory and therapeutic practice&#46; For TNBC specifically&#44; different research groups that used the information generated by microarrays obtained results varying from one group to another and in some cases these results have not been able to be validated&#46; This could be a result of the inherent heterogeneity of TNBC or each experiment design&#39;s own limitations&#44; such as&#58; &#40;1&#41; the use of large data base retrospective cohorts&#44; where TNBC&#39;s classification is based solely on the information obtained from the gene expression profile data&#44; this methodology is not the standard in clinical practice&#46; Also&#44; this information shows limitations due to how varying the data collection and sample management methods are used &#40;in some cases paraffin-embedded tissue was utilized&#44; others utilized fresh tissue&#44; etc&#46;&#41; to feed the databases that are afterwards referenced by other researchers&#59; &#40;2&#41; limited gene expression analysis of a determined number of genes&#44; instead of conducting a global analysis of gene expression&#59; &#40;3&#41; previous works and researches compared TNBC gene expression profiles vs other BC subtypes&#44; or TNBC vs normal tissue&#44; which does not unify stratification criteria&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">In Mexico&#44; there are few research papers which report the analysis of TNBC expression profiles This is concerning&#44; since this type of BC jeopardizes a considerable amount of cases among the Mexican population&#44; hence it is necessary to increase efforts in the search of biomarkers or possible therapeutic targets which can be validated in our population&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Funding</span><p id="par0265" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleGrantSponsor" id="gs1">CONACyT Fondo Salud</span><span class="elsevierStyleGrantNumber" refid="gs1">162301</span> and <span class="elsevierStyleGrantSponsor" id="gs2">Convocatoria de Becas Nacionales</span><span class="elsevierStyleGrantNumber" refid="gs2">2014-370024</span>&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of interest</span><p id="par0270" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "titulo" => "Introduction"
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        3 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Breast cancer classification"
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        4 => array:2 [
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          "titulo" => "Prognostic value of genomic signatures in BC"
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          "titulo" => "Triple negative breast cancer &#40;TNBC&#41;"
          "secciones" => array:4 [
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              "identificador" => "sec0025"
              "titulo" => "TNBC risk factors"
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            1 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Molecular classification of TNBC subtypes"
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            2 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "The search for TNBC biomarkers"
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            3 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "TNBC treatment"
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        6 => array:2 [
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          "titulo" => "Conclusions"
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          "titulo" => "Funding"
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          "identificador" => "sec0055"
          "titulo" => "Conflict of interest"
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          "titulo" => "References"
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    "fechaRecibido" => "2015-12-15"
    "fechaAceptado" => "2016-05-04"
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        0 => array:4 [
          "clase" => "keyword"
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            0 => "Triple negative breast cancer"
            1 => "Gene expression"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Triple negative breast cancer &#40;TNBC&#41; is a subtype of breast cancer &#40;BC&#41; with a heterogeneous nature that stains negatively for estrogen receptor &#40;ER&#41;&#44; progesterone receptor &#40;PR&#41; and human epidermal growth factor 2 &#40;HER2&#41; during immunohistochemistry&#46; Approximately 15&#8211;20&#37; of all cases of breast cancer are triple negative phenotypes&#46; Compared to patients with hormone receptor-positive cancer&#44; TNBC patients are typically younger &#40;&#60;50 years&#41;&#44; African American&#44; and have a high incidence of mutations in BRCA1&#47;2 genes&#46; To date&#44; not a single targeted therapy has been approved for TNBC treatment&#44; and cytotoxic chemotherapy remains as the standard systemic treatment&#44; meaning that TNBC is an aggressive subtype of breast cancer with a poor prognosis&#46; In this review&#44; the literature search was done up to date on which gene expression profile of TNBC has been analyzed in order to identify the consensus on molecular mechanisms involved in carcinogenesis and&#47;or the prognostic markers of the disease&#46; In conclusion&#44; these studies have reported that TNBC is composed of several clusters or genomic signatures as basal keratins&#46; They have also reported on their proliferation&#44; luminal&#47;basal apocrine&#44; regulatory interferon&#44; immune cells&#47;immunoglobulin related to stem cells&#44; epithelial-mesenchymal&#44; androgen receptor and angiogenesis&#46; However&#44; not all research groups have reported reproducible results&#46; This confirms the heterogeneous nature of TNBC and the need for research on uniform selection criteria&#46; However&#44; these discoveries have led to the proposal of new treatments&#44; such as the addition of platinum salts&#44; new combinations of therapeutic agents&#44; some targeted therapies such as PARP inhibitors&#44; and PI3K and androgen antagonists&#46; There is no doubt that a better understanding of the nature of TNBC will allow individualized and more effective therapies&#46;</p></span>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Breast cancer classification example using PAM50&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Lehman&#39;s triple negative breast cancer classification&#44; gene ontology and proportion&#46; TNBC&#44; triple negative breast cancer&#59; BL1&#44; basal like 1&#59; BL2&#44; basal like 2&#59; IM&#44; immunomodulatory&#59; M&#44; mesenchymal&#59; MSL&#44; mesenchymal stem cell-type&#59; LAR&#44; androgen luminal receptor&#59; MET&#44; mesenchymal epithelial transition&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Observation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Main genes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Signature objective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Experiment design</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sample characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Comparison&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rody&#44; 2011<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">59</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16 meta-genes&#58; basal phenotype&#44; androgen receptor signaling&#44; diverse immune cells&#44; stroma&#44; Claudine CD24&#44; blood cell markers and adipocytes&#44; inflammation and angiogenesis &#40;VEGF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">EPHB3&#44; GABRP&#44; AR&#44; FOXA1&#44; IgG&#44; TCR&#44; LCK&#44; ITK&#44; HLA-DR&#44; -DM&#44; -DP&#44; -DQ&#44; HLA-A&#44; -B&#44; -C&#44; -E&#44; -F&#44; -G&#44; OAS1&#44; OAS2&#44; OAS3&#44; MX1&#44; Decorin&#44; Osteonectin&#44; Fibronectin&#46;<br>COL5A1&#44; CLDN3&#44; CLDN4&#44; CD24&#44; ELF3&#44; BUB1&#44; CDC2&#44; STK6&#44; BIRC5&#44; TOP2A&#44; HBA1&#44; HBA2&#44; HBB&#44; FABP4&#44; PLIN&#44; ADIPOQ&#44; ADH1B&#44; VEGF&#44; adrenomedulina&#44; ANGPTL4&#44; IL-8&#44; CXCL1&#44; CXCL2&#44; HOXA-4&#44; -5&#44; -7&#44; -9&#44; -10&#44; -11&#44; Histones H2A&#44; H2B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prognosis&#47;therapeutic target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Public database&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">394 TNBC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Karn&#44; 2011<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">71</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 signatures &#40;26 main genes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL8&#44; SCD&#44; AQP3&#44; SERPINE1&#44; LYPDC1&#44; PGK1&#44; SEC23A&#44; SNAPC1&#44; SNF7DC2&#44; SORT1&#44; SPOCK&#44; SRPX2&#44; STC1&#44; STMN2&#44; SYNCRIP&#44; TAX1BP3&#44; TBC1D22B&#44; TGFB2&#44; TGFBI&#44; THBS1&#44; TIAM1&#44; TLE6&#44; TNFAIP1&#44; TNFRSF10B&#44; TRIM23&#44; TSGA10&#44; TXNDC9&#44; U2AF1L1&#44; ULBP2&#44; UQCRC1&#44; VLDLR&#44; VMD2&#44; WFDC1&#44; WWTR1&#44; ZA20D1&#44; ZP2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prognosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Public database&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">394 TNBC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cascione&#44; 2013<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">72</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#215; microRNA signatures and 4 gene subgroups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">miR-16&#44; 155&#44; 125b&#44; 374a and miR-16&#44; 125b&#44; 374a&#44; 374b&#44; 421&#44; 655&#44; 497<br>Molecular subgroup 1&#58; SPP1&#44; MMP9&#44; MYB12&#44; BIRC5&#44; TOP2A&#44; CDC2&#44; CDKN2A&#46; Molecular subgroup 2&#58; BCL2&#44; EGF&#44; ERBB4&#44; AR&#44; ESR1&#44; IL1A&#44; FGFR2&#44; WT1&#44; MYC&#44; FGF2&#44; AKT1&#44; CASP10&#46; Molecular subgroup 3&#58; MET&#44; L1CAM&#44; IGFBP3&#46; Molecular subgroup 4&#58; TIMP1&#44; TIMP2&#44; CDKN1A&#44; CCND2&#44; MAP3K8&#44; CAV1&#44; LAMB1&#44; JUN&#44; CEBPA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sub-classification&#47;therapeutic target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Paraffin-embedded tissue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TNBC vs Adjacent tissue and lymph node injuries&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Komatsu&#44; 2013<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">73</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">322 unregulated genes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Main overexpressed genes&#58; UBE2C&#44; S100P&#44; UCHL1&#44; PTTG1&#44; UBE2T&#44; SIX1&#44; PRC1&#44; TOP2A&#44; HORMAD1&#44; FABP5&#44; ATAD2&#46; Main sub-expressed genes&#58; PIP&#44; DNAL11&#44; WIF1&#44; SCUBE2&#44; TBC1D9&#44; TFF3&#44; ERBB4&#44; GATA3&#44; MLPH&#46; LAMAB&#44; LTBP2&#44; LIFR&#44; LRP2&#44; MASP2&#44; MATN2&#44; MGP&#44; NTN4&#44; NRG1&#44; PTHLH&#44; PI15&#44; PLAT&#44; PDGFA&#44; PTN&#44; PIGR&#44; PIP&#44; SCGB1D1&#44; SCGB1D2&#44; SCGB3A1&#44; SEMA3G&#44; STC2&#44; THSD4&#44; TFF3&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Therapeutic target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fresh tissue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TNBC vs epithelial ductal cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Al-Ejeh&#44; 2014<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">74</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 genes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MAPT&#44; MYB&#44; MELK&#44; MCM10&#44; CENPA&#44; EXO1&#44; TTK and KIF2C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prognosis&#47;therapeutic target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Meta-analysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CMTN vs CMnTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Khaled&#44; 2015<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">75</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 gene&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BCL11A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Therapeutic target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Public data base&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CMTN vs CMnTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">He&#44; 2015<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">76</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 genes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DUSP1 and FOXA1&#46; DUSP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Therapeutic targets&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Public data base&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CMTN vs CMnTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pacheco-Velazquez&#44; 2014<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">77</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 genes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">HIF-1&#945;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>c-MYC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>2OGDH<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>E-cadherina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prognosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fresh tissue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CMTN vs CMnTN vs Normal tissue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:77 [
            0 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Breast cancer statistics&#44; 2013"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46; DeSantis"
                            1 => "Surveillance and Health Services Research ACSEAG"
                            2 => "J&#46; Ma"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3322/caac.21203"
                      "Revista" => array:6 [
                        "tituloSerie" => "CA Cancer J Clin"
                        "fecha" => "2015"
                        "volumen" => "64"
                        "paginaInicial" => "52"
                        "paginaFinal" => "62"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24114568"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Fact Sheets by Cancer&#46; 2015&#59; <a id="intr0005" class="elsevierStyleInterRef" href="http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx">http&#58;&#47;&#47;globocan&#46;iarc&#46;fr&#47;Pages&#47;fact&#95;sheets&#95;cancer&#46;aspx</a>&#46;"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Mexico &#8211; INEGI &#8211; Estadasticas a proposito del Dia Mundial de la lucha contra el cancer de mama&#46; 19 October 2016&#59; <a id="intr0010" class="elsevierStyleInterRef" href="http://mx.noticiasol.com/inegi/estadsticas-a-propsito-del-da-mundial-de-la-lucha-contra-el-cncer-de-mama--19-de-octubre.html">http&#58;&#47;&#47;mx&#46;noticiasol&#46;com&#47;inegi&#47;estadsticas-a-propsito-del-da-mundial-de-la-lucha-contra-el-cncer-de-mama--19-de-octubre&#46;html</a>&#46;"
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biomarkers in triple negative breast cancer&#58; a review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "B&#46;S&#46; Yadav"
                            1 => "P&#46; Chanana"
                            2 => "S&#46; Jhamb"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.5306/wjco.v6.i6.252"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Clin Oncol"
                        "fecha" => "2015"
                        "volumen" => "6"
                        "paginaInicial" => "252"
                        "paginaFinal" => "263"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26677438"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Personalizing the treatment of women with early breast cancer&#58; highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Goldhirsch"
                            1 => "E&#46;P&#46; Winer"
                            2 => "A&#46;S&#46; Coates"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mdt303"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2013"
                        "volumen" => "24"
                        "paginaInicial" => "2206"
                        "paginaFinal" => "2223"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23917950"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Issues and updates&#58; evaluating estrogen receptor-&#945;&#44; progesterone receptor&#44; and HER2 in breast cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46;C&#46; Allred"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/modpathol.2010.55"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mod Pathol"
                        "fecha" => "2010"
                        "volumen" => "23"
                        "paginaInicial" => "s52"
                        "paginaFinal" => "s59"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20436503"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Integrative investigation on breast cancer in ER&#44; PR and HER2-defined subgroups using mRNA and miRNA expression profiling"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "X&#46; Dai"
                            1 => "A&#46; Chen"
                            2 => "Z&#46; Bai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/srep06566"
                      "Revista" => array:5 [
                        "tituloSerie" => "Sci Rep"
                        "fecha" => "2014"
                        "volumen" => "4"
                        "paginaInicial" => "6566"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25338681"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Molecular portraits revealing the heterogeneity of breast tumor subtypes defined using immunohistochemistry markers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "X&#46; Dai"
                            1 => "Y&#46; Li"
                            2 => "Z&#46; Bai"
                            3 => "X&#46;Q&#46; Tang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/srep14499"
                      "Revista" => array:6 [
                        "tituloSerie" => "Sci Rep"
                        "fecha" => "2015"
                        "volumen" => "5"
                        "paginaInicial" => "14499"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26404658"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0264410X15014371"
                          "estado" => "S300"
                          "issn" => "0264410X"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Triple-negative breast cancer&#58; advancements in characterization and treatment approach"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46; Hurvitz"
                            1 => "M&#46; Mead"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/GCO.0000000000000239"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Obstet Gynecol"
                        "fecha" => "2016"
                        "volumen" => "28"
                        "paginaInicial" => "59"
                        "paginaFinal" => "69"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26694831"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Molecular portraits of human breast tumours"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46;M&#46; Perou"
                            1 => "T&#46; S&#248;rlie"
                            2 => "M&#46;B&#46; Eisen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/35021093"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2000"
                        "volumen" => "406"
                        "paginaInicial" => "747"
                        "paginaFinal" => "752"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10963602"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "T&#46; Sorlie"
                            1 => "C&#46;M&#46; Perou"
                            2 => "R&#46; Tibshirani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.191367098"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci U S A"
                        "fecha" => "2001"
                        "volumen" => "98"
                        "paginaInicial" => "10869"
                        "paginaFinal" => "10874"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11553815"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "E&#46;A&#46; Rakha"
                            1 => "T&#46;C&#46; Putti"
                            2 => "D&#46;M&#46; Abd El-Rehim"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/path.1916"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pathol"
                        "fecha" => "2006"
                        "volumen" => "208"
                        "paginaInicial" => "495"
                        "paginaFinal" => "506"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16429394"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46; van de Rijn"
                            1 => "C&#46;M&#46; Perou"
                            2 => "R&#46; Tibshirani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0002-9440(10)64476-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Pathol"
                        "fecha" => "2002"
                        "volumen" => "161"
                        "paginaInicial" => "1991"
                        "paginaFinal" => "1996"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12466114"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival&#58; a collaborative analysis of data for 10&#44;159 cases from 12 studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "F&#46;M&#46; Blows"
                            1 => "K&#46;E&#46; Driver"
                            2 => "M&#46;K&#46; Schmidt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pmed.1000279"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS Med"
                        "fecha" => "2010"
                        "volumen" => "7"
                        "paginaInicial" => "e1000279"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20520800"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Correlation of ER&#44; PR and HER-2&#47;Neu with other prognostic factors in infiltrating ductal carcinoma of breast"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Siadati"
                            1 => "M&#46; Sharbatdaran"
                            2 => "N&#46; Nikbakhsh"
                            3 => "N&#46; Ghaemian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Iran J Pathol"
                        "fecha" => "2015"
                        "volumen" => "10"
                        "paginaInicial" => "221"
                        "paginaFinal" => "226"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26351488"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Strategies for subtypes &#8211; dealing with the diversity of breast cancer&#58; highlights of the St&#46; Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Goldhirsch"
                            1 => "W&#46;C&#46; Wood"
                            2 => "A&#46;S&#46; Coates"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mdr304"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2011"
                        "volumen" => "22"
                        "paginaInicial" => "1736"
                        "paginaFinal" => "1747"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21709140"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A gene-expression signature as a predictor of survival in breast cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46;J&#46; van de Vijver"
                            1 => "Y&#46;D&#46; He"
                            2 => "L&#46;J&#46; van&#8217;t Veer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa021967"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2002"
                        "volumen" => "347"
                        "paginaInicial" => "1999"
                        "paginaFinal" => "2009"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12490681"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gene expression profiling predicts clinical outcome of breast cancer"
                      "autores" => array:1 [
                        0 => array:2 [
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                          "autores" => array:3 [
                            0 => "L&#46;J&#46; van&#8217;t Veer"
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                            2 => "M&#46;J&#46; van de Vijver"
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                    0 => array:2 [
                      "doi" => "10.1038/415530a"
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                        "tituloSerie" => "Nature"
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                        "volumen" => "415"
                        "paginaInicial" => "530"
                        "paginaFinal" => "536"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11823860"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "A multigene assay to predict recurrence of tamoxifen-treated&#44; node-negative breast cancer"
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                          "etal" => true
                          "autores" => array:3 [
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                            1 => "S&#46; Shak"
                            2 => "G&#46; Tang"
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                      ]
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                  "host" => array:1 [
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                      "doi" => "10.1056/NEJMoa041588"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "351"
                        "paginaInicial" => "2817"
                        "paginaFinal" => "2826"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15591335"
                            "web" => "Medline"
                          ]
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                  ]
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              ]
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              "identificador" => "bib0485"
              "etiqueta" => "20"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gene expression and benefit of chemotherapy in women with node-negative&#44; estrogen receptor-positive breast cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46; Paik"
                            1 => "G&#46; Tang"
                            2 => "S&#46; Shak"
                          ]
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2005.04.7985"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2006"
                        "volumen" => "24"
                        "paginaInicial" => "3726"
                        "paginaFinal" => "3734"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16720680"
                            "web" => "Medline"
                          ]
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                        "itemHostRev" => array:3 [
                          "pii" => "S0264410X14000826"
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                          "issn" => "0264410X"
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              "identificador" => "bib0490"
              "etiqueta" => "21"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1&#8211;3 positive lymph nodes in an independent validation study"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46; Mook"
                            1 => "M&#46;K&#46; Schmidt"
                            2 => "G&#46; Viale"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10549-008-0130-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Breast Cancer Res Treat"
                        "fecha" => "2009"
                        "volumen" => "116"
                        "paginaInicial" => "295"
                        "paginaFinal" => "302"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18661261"
                            "web" => "Medline"
                          ]
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            21 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46;A&#46; Drukker"
                            1 => "J&#46;M&#46; Bueno-de-Mesquita"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ijc.28082"
                      "Revista" => array:7 [
                        "tituloSerie" => "Int J Cancer"
                        "fecha" => "2013"
                        "volumen" => "133"
                        "paginaInicial" => "929"
                        "paginaFinal" => "936"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23371464"
                            "web" => "Medline"
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                          "issn" => "07351097"
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              "identificador" => "bib0500"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46; Knauer"
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                            2 => "E&#46;J&#46; Rutgers"
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Breast Cancer Res Treat"
                        "fecha" => "2010"
                        "volumen" => "120"
                        "paginaInicial" => "655"
                        "paginaFinal" => "661"
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                  ]
                ]
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              "identificador" => "bib0505"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Supervised risk predictor of breast cancer based on intrinsic subtypes"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;S&#46; Parker"
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                            2 => "M&#46;C&#46; Cheang"
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                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2009"
                        "volumen" => "27"
                        "paginaInicial" => "1160"
                        "paginaFinal" => "1167"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19204204"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46; Martin"
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                            2 => "A&#46; Rodriguez-Lescure"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10549-013-2416-2"
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                        "tituloSerie" => "Breast Cancer Res Treat"
                        "fecha" => "2013"
                        "volumen" => "138"
                        "paginaInicial" => "457"
                        "paginaFinal" => "466"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23423445"
                            "web" => "Medline"
                          ]
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                ]
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              "identificador" => "bib0515"
              "etiqueta" => "26"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2013"
                        "volumen" => "31"
                        "paginaInicial" => "2783"
                        "paginaFinal" => "2790"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23816962"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0520"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognostic utility of the breast cancer index and comparison to Adjuvant&#33; Online in a clinical case series of early breast cancer"
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                          "etal" => true
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                    0 => array:2 [
                      "doi" => "10.1186/bcr3038"
                      "Revista" => array:5 [
                        "tituloSerie" => "Breast Cancer Res"
                        "fecha" => "2011"
                        "volumen" => "13"
                        "paginaInicial" => "R98"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21999244"
                            "web" => "Medline"
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              "identificador" => "bib0525"
              "etiqueta" => "28"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "A new molecular predictor of distant recurrence in ER-positive&#44; HER2-negative breast cancer adds independent information to conventional clinical risk factors"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
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                            2 => "R&#46; Jakesz"
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-11-0926"
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                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2011"
                        "volumen" => "17"
                        "paginaInicial" => "6012"
                        "paginaFinal" => "6020"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21807638"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Prognostic value of a combined estrogen receptor&#44; progesterone receptor&#44; Ki-67&#44; and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer"
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                        0 => array:2 [
                          "etal" => true
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2010.31.2835"
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                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2011"
                        "volumen" => "29"
                        "paginaInicial" => "4273"
                        "paginaFinal" => "4278"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21990413"
                            "web" => "Medline"
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              "identificador" => "bib0535"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Molecular classification and molecular forecasting of breast cancer&#58; ready for clinical application&#63;"
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                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;D&#46; Brenton"
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                    0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2005"
                        "volumen" => "23"
                        "paginaInicial" => "7350"
                        "paginaFinal" => "7360"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16145060"
                            "web" => "Medline"
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                ]
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              "identificador" => "bib0540"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer"
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                            0 => "W&#46;D&#46; Foulkes"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Natl Cancer Inst"
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                        "volumen" => "95"
                        "paginaInicial" => "1482"
                        "paginaFinal" => "1485"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14519755"
                            "web" => "Medline"
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                  ]
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              "identificador" => "bib0545"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Descriptive analysis of estrogen receptor &#40;ER&#41;-negative&#44; progesterone receptor &#40;PR&#41;-negative&#44; and HER2-negative invasive breast cancer&#44; the so-called triple-negative phenotype&#58; a population-based study from the California Cancer Registry"
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                          "etal" => false
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                    0 => array:2 [
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                        "tituloSerie" => "Cancer"
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                        "paginaInicial" => "1721"
                        "paginaFinal" => "1728"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17387718"
                            "web" => "Medline"
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              "identificador" => "bib0550"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The prognostic importance of triple negative breast carcinoma"
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                        "tituloSerie" => "Breast"
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                        "volumen" => "17"
                        "paginaInicial" => "341"
                        "paginaFinal" => "346"
                        "link" => array:1 [
                          0 => array:2 [
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                            "web" => "Medline"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer"
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                  "host" => array:1 [
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                        "tituloSerie" => "J Natl Cancer Inst"
                        "fecha" => "2011"
                        "volumen" => "103"
                        "paginaInicial" => "470"
                        "paginaFinal" => "477"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21346227"
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                    0 => array:2 [
                      "titulo" => "Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer"
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                        "tituloSerie" => "Breast Cancer Res Treat"
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                        "paginaFinal" => "167"
                        "link" => array:1 [
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                    0 => array:2 [
                      "titulo" => "Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger"
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                      "doi" => "10.1007/s10549-011-1616-x"
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                        "tituloSerie" => "Breast Cancer Res Treat"
                        "fecha" => "2011"
                        "volumen" => "130"
                        "paginaInicial" => "587"
                        "paginaFinal" => "597"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21667121"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "A case&#8211;control study of reproductive factors associated with subtypes of breast cancer in Northeast China"
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                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46; Xing"
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                        "tituloSerie" => "Med Oncol"
                        "fecha" => "2010"
                        "volumen" => "27"
                        "paginaInicial" => "926"
                        "paginaFinal" => "931"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19771534"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0575"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Body size&#44; physical activity&#44; and risk of triple-negative and estrogen receptor-positive breast cancer"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46;I&#46; Phipps"
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                            2 => "R&#46; Prentice"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer Epidemiol Biomark Prev"
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                        "volumen" => "20"
                        "paginaInicial" => "454"
                        "paginaFinal" => "463"
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673611606879"
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                          "issn" => "01406736"
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            38 => array:3 [
              "identificador" => "bib0580"
              "etiqueta" => "39"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46;L&#46; Kwan"
                            1 => "L&#46;H&#46; Kushi"
                            2 => "E&#46; Weltzien"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
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                      "Revista" => array:5 [
                        "tituloSerie" => "Breast Cancer Res"
                        "fecha" => "2009"
                        "volumen" => "11"
                        "paginaInicial" => "R31"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19463150"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0585"
              "etiqueta" => "40"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Metabolic syndrome&#44; insulin resistance&#44; and mammographic density in pre- and postmenopausal women"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "B&#46;K&#46; Kim"
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                            2 => "J&#46; Ahn"
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                      ]
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                  "host" => array:1 [
                    0 => array:2 [
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                      "Revista" => array:6 [
                        "tituloSerie" => "Breast Cancer Res Treat"
                        "fecha" => "2015"
                        "volumen" => "153"
                        "paginaInicial" => "425"
                        "paginaFinal" => "434"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26277917"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0590"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The association of metabolic syndrome with triple-negative breast cancer"
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                          "etal" => false
                          "autores" => array:4 [
                            0 => "B&#46; Maiti"
                            1 => "M&#46;N&#46; Kundranda"
                            2 => "T&#46;P&#46; Spiro"
                            3 => "H&#46;A&#46; Daw"
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                    0 => array:2 [
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                        "tituloSerie" => "Breast Cancer Res Treat"
                        "fecha" => "2010"
                        "volumen" => "121"
                        "paginaInicial" => "479"
                        "paginaFinal" => "483"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19851862"
                            "web" => "Medline"
                          ]
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                      ]
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                  ]
                ]
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            41 => array:3 [
              "identificador" => "bib0595"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metabolic syndrome and triple-negative breast cancer&#58; a new paradigm"
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;A&#46; Davis"
                            1 => "V&#46;G&#46; Kaklamani"
                          ]
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                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Breast Cancer"
                        "fecha" => "2012"
                        "volumen" => "2012"
                        "paginaInicial" => "1"
                        "paginaFinal" => "10"
                      ]
                    ]
                  ]
                ]
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            42 => array:3 [
              "identificador" => "bib0600"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Insulin-like growth factor-dependent proliferation and survival of triple-negative breast cancer cells&#58; implications for therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Z&#46; Davison"
                            1 => "G&#46;E&#46; de Blacquiere"
                            2 => "B&#46;R&#46; Westley"
                            3 => "F&#46;E&#46; May"
                          ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Neoplasia"
                        "fecha" => "2011"
                        "volumen" => "13"
                        "paginaInicial" => "504"
                        "paginaFinal" => "515"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21677874"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            43 => array:3 [
              "identificador" => "bib0605"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Higher population-based incidence rates of triple-negative breast cancer among young African-American women&#58; implications for breast cancer screening recommendations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "K&#46;C&#46; Amirikia"
                            1 => "P&#46; Mills"
                            2 => "J&#46; Bush"
                            3 => "L&#46;A&#46; Newman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cncr.25862"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "2011"
                        "volumen" => "117"
                        "paginaInicial" => "2747"
                        "paginaFinal" => "2753"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21656753"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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            44 => array:3 [
              "identificador" => "bib0610"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Triple receptor-negative breast cancer&#58; the effect of race on response to primary systemic treatment and survival outcomes"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46; Dawood"
                            1 => "K&#46; Broglio"
                            2 => "S&#46;W&#46; Kau"
                          ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2008.17.9952"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2009"
                        "volumen" => "27"
                        "paginaInicial" => "220"
                        "paginaFinal" => "226"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19047281"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            45 => array:3 [
              "identificador" => "bib0615"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ethnicity and breast cancer&#58; factors influencing differences in incidence and outcome"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "R&#46;T&#46; Chlebowski"
                            1 => "Z&#46; Chen"
                            2 => "G&#46;L&#46; Anderson"
                          ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/jnci/dji064"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Natl Cancer Inst"
                        "fecha" => "2005"
                        "volumen" => "97"
                        "paginaInicial" => "439"
                        "paginaFinal" => "448"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15770008"
                            "web" => "Medline"
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                        "itemHostRev" => array:3 [
                          "pii" => "S0264410X15000304"
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                          "issn" => "0264410X"
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            46 => array:3 [
              "identificador" => "bib0620"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Breast cancer classification according to immunohistochemistry markers&#58; subtypes and association with clinicopathologic variables in a peruvian hospital database"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
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                            2 => "W&#46;R&#46; Cruz"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3816/CBC.2010.n.038"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Breast Cancer"
                        "fecha" => "2010"
                        "volumen" => "10"
                        "paginaInicial" => "294"
                        "paginaFinal" => "300"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20705562"
                            "web" => "Medline"
                          ]
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                ]
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            47 => array:3 [
              "identificador" => "bib0625"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunohistochemical profile and clinical-pathological variables in breast cancer"
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                            2 => "R&#46;W&#46; Diniz"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Assoc Med Bras"
                        "fecha" => "2012"
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                        "paginaInicial" => "178"
                        "paginaFinal" => "187"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22569612"
                            "web" => "Medline"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Investig Clin"
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                        "volumen" => "54"
                        "paginaInicial" => "406"
                        "paginaFinal" => "416"
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              "identificador" => "bib0635"
              "etiqueta" => "50"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Triple-negative breast cancer in Hispanic patients&#58; high prevalence&#44; poor prognosis&#44; and association with menopausal status&#44; body mass index&#44; and parity"
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                        0 => array:2 [
                          "etal" => true
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cncr.25961"
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                        "tituloSerie" => "Cancer"
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                        "volumen" => "117"
                        "paginaInicial" => "3658"
                        "paginaFinal" => "3669"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21387260"
                            "web" => "Medline"
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              "identificador" => "bib0640"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Is triple negative a prognostic factor in breast cancer&#63;"
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                          "autores" => array:2 [
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "Breast Cancer"
                        "fecha" => "2008"
                        "volumen" => "15"
                        "paginaInicial" => "303"
                        "paginaFinal" => "308"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18369692"
                            "web" => "Medline"
                          ]
                        ]
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                    ]
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                ]
              ]
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            51 => array:3 [
              "identificador" => "bib0645"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Triple-negative breast cancer&#58; clinical features and patterns of recurrence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "R&#46; Dent"
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                            2 => "K&#46;I&#46; Pritchard"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-06-3045"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2007"
                        "volumen" => "13"
                        "paginaInicial" => "4429"
                        "paginaFinal" => "4434"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17671126"
                            "web" => "Medline"
                          ]
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                    ]
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                ]
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            52 => array:3 [
              "identificador" => "bib0650"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                            1 => "J&#46; Cuartero"
                            2 => "J&#46; Hanson"
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                            4 => "D&#46; Lesniak"
                            5 => "S&#46; Sabri"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2010.33.4714"
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                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2011"
                        "volumen" => "29"
                        "paginaInicial" => "2852"
                        "paginaFinal" => "2858"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21670451"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0655"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Breast cancer subtype approximated by estrogen receptor&#44; progesterone receptor&#44; and HER-2 is associated with local and distant recurrence after breast-conserving therapy"
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                        0 => array:2 [
                          "etal" => true
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                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2008"
                        "volumen" => "26"
                        "paginaInicial" => "2373"
                        "paginaFinal" => "2378"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18413639"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0660"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "H&#46; Masuda"
                            1 => "K&#46;A&#46; Baggerly"
                            2 => "Y&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-13-0799"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2013"
                        "volumen" => "19"
                        "paginaInicial" => "5533"
                        "paginaFinal" => "5540"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23948975"
                            "web" => "Medline"
                          ]
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            55 => array:3 [
              "identificador" => "bib0665"
              "etiqueta" => "56"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "G&#46; von Minckwitz"
                            1 => "M&#46; Untch"
                            2 => "J&#46;U&#46; Blohmer"
                          ]
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1200/JCO.2011.38.8595"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2012"
                        "volumen" => "30"
                        "paginaInicial" => "1796"
                        "paginaFinal" => "1804"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22508812"
                            "web" => "Medline"
                          ]
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                          "pii" => "S0264410X15000353"
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                          "issn" => "0264410X"
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            56 => array:3 [
              "identificador" => "bib0670"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46; Liedtke"
                            1 => "C&#46; Mazouni"
                            2 => "K&#46;R&#46; Hess"
                          ]
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                      ]
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                    0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2008"
                        "volumen" => "26"
                        "paginaInicial" => "1275"
                        "paginaFinal" => "1281"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18250347"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            57 => array:3 [
              "identificador" => "bib0675"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gene expression profiling and histopathological characterization of triple-negative&#47;basal-like breast carcinomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "B&#46; Kreike"
                            1 => "M&#46; van Kouwenhove"
                            2 => "H&#46; Horlings"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/bcr1771"
                      "Revista" => array:5 [
                        "tituloSerie" => "Breast Cancer Res"
                        "fecha" => "2007"
                        "volumen" => "9"
                        "paginaInicial" => "R65"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17910759"
                            "web" => "Medline"
                          ]
                        ]
                      ]
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            58 => array:3 [
              "identificador" => "bib0680"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A clinically relevant gene signature in triple negative and basal-like breast cancer"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Rody"
                            1 => "T&#46; Karn"
                            2 => "C&#46; Liedtke"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/bcr3035"
                      "Revista" => array:6 [
                        "tituloSerie" => "Breast Cancer Res"
                        "fecha" => "2011"
                        "volumen" => "13"
                        "paginaInicial" => "R97"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21978456"
                            "web" => "Medline"
                          ]
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                          "pii" => "S0264410X14017216"
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                          "issn" => "0264410X"
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            59 => array:3 [
              "identificador" => "bib0685"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "B&#46;D&#46; Lehmann"
                            1 => "J&#46;A&#46; Bauer"
                            2 => "X&#46; Chen"
                          ]
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                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI45014"
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                        "tituloSerie" => "J Clin Investig"
                        "fecha" => "2011"
                        "volumen" => "121"
                        "paginaInicial" => "2750"
                        "paginaFinal" => "2767"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21633166"
                            "web" => "Medline"
                          ]
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                ]
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            60 => array:3 [
              "identificador" => "bib0690"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46;D&#46; Burstein"
                            1 => "A&#46; Tsimelzon"
                            2 => "G&#46;M&#46; Poage"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-14-0432"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2015"
                        "volumen" => "21"
                        "paginaInicial" => "1688"
                        "paginaFinal" => "1698"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25208879"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            61 => array:3 [
              "identificador" => "bib0695"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The triple negative paradox&#58; primary tumor chemosensitivity of breast cancer subtypes"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "L&#46;A&#46; Carey"
                            1 => "E&#46;C&#46; Dees"
                            2 => "L&#46; Sawyer"
                          ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-06-1109"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2007"
                        "volumen" => "13"
                        "paginaInicial" => "2329"
                        "paginaFinal" => "2334"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17438091"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0700"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Higher locoregional recurrence rate for triple-negative breast cancer following neoadjuvant chemotherapy&#44; surgery and radiotherapy"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46; Zhang"
                            1 => "S&#46; Wang"
                            2 => "H&#46;P&#46; Israel"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s40064-015-1116-2"
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                        "tituloSerie" => "SpringerPlus"
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                        "volumen" => "4"
                        "paginaInicial" => "386"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26240784"
                            "web" => "Medline"
                          ]
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                  ]
                ]
              ]
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            63 => array:3 [
              "identificador" => "bib0705"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Targeted approaches to triple-negative breast cancer&#58; current practice and future directions"
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                          "etal" => false
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                            3 => "F&#46; Lumachi"
                            4 => "V&#46; Zagonel"
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Curr Med Chem"
                        "fecha" => "2013"
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                        "paginaInicial" => "605"
                        "paginaFinal" => "612"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23278396"
                            "web" => "Medline"
                          ]
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                          "pii" => "S0264410X14016934"
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                          "issn" => "0264410X"
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            64 => array:3 [
              "identificador" => "bib0710"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Changing end points in breast-cancer drug approval &#8211; the Avastin story"
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                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2011"
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                        "paginaInicial" => "e2"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21707384"
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            65 => array:3 [
              "identificador" => "bib0715"
              "etiqueta" => "66"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The PARP inhibitor AZD2281 &#40;Olaparib&#41; induces autophagy&#47;mitophagy in BRCA1 and BRCA2 mutant breast cancer cells"
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                    0 => array:2 [
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                        "tituloSerie" => "Int J Oncol"
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                        "paginaInicial" => "262"
                        "paginaFinal" => "268"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25975349"
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            66 => array:3 [
              "identificador" => "bib0720"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "TBCRC 001&#58; randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer"
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                    0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
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                        "volumen" => "30"
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                        "paginaFinal" => "2623"
                        "link" => array:1 [
                          0 => array:2 [
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              "identificador" => "bib0725"
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                        "tituloSerie" => "Cancer Res"
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                        "paginaFinal" => "2559"
                        "link" => array:1 [
                          0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
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                        "paginaInicial" => "4536"
                        "paginaFinal" => "4541"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19687332"
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              "identificador" => "bib0735"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Phase II trial of bicalutamide in patients with androgen receptor-positive&#44; estrogen receptor-negative metastatic Breast Cancer"
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                        "tituloSerie" => "Clin Cancer Res"
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                        "paginaFinal" => "5512"
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                          0 => array:2 [
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                0 => array:2 [
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                        "paginaInicial" => "478"
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                        "link" => array:1 [
                          0 => array:2 [
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                        "paginaInicial" => "2549"
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Article information

ISSN: 16655796
Original language: English

DOI:10.1016/j.rmu.2016.05.007

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Year/Month	Html	Pdf	Total

2024 November	6	0	6
2024 October	52	10	62
2024 September	68	4	72
2024 August	55	7	62
2024 July	51	13	64
2024 June	42	6	48
2024 May	59	10	69
2024 April	66	14	80
2024 March	98	6	104
2024 February	110	21	131
2024 January	88	9	97
2023 December	90	17	107
2023 November	110	17	127
2023 October	104	23	127
2023 September	61	19	80
2023 August	62	13	75
2023 July	89	16	105
2023 June	65	12	77
2023 May	104	31	135
2023 April	85	24	109
2023 March	86	10	96
2023 February	68	18	86
2023 January	55	17	72
2022 December	95	16	111
2022 November	108	33	141
2022 October	90	12	102
2022 September	100	33	133
2022 August	106	34	140
2022 July	78	38	116
2022 June	102	24	126
2022 May	127	28	155
2022 April	169	25	194
2022 March	259	34	293
2022 February	257	21	278
2022 January	275	24	299
2021 December	213	45	258
2021 November	233	30	263
2021 October	192	48	240
2021 September	199	68	267
2021 August	227	52	279
2021 July	184	49	233
2021 June	145	43	188
2021 May	183	40	223
2021 April	495	119	614
2021 March	267	68	335
2021 February	186	42	228
2021 January	182	47	229
2020 December	173	44	217
2020 November	180	45	225
2020 October	98	21	119
2020 September	113	32	145
2020 August	133	29	162
2020 July	122	34	156
2020 June	137	31	168
2020 May	191	56	247
2020 April	171	51	222
2020 March	200	57	257
2020 February	178	48	226
2020 January	170	59	229
2019 December	115	44	159
2019 November	99	23	122
2019 October	116	40	156
2019 September	112	14	126
2019 August	81	27	108
2019 July	68	19	87
2019 June	114	32	146
2019 May	144	46	190
2019 April	111	25	136
2019 March	59	17	76
2019 February	45	10	55
2019 January	48	8	56
2018 December	49	7	56
2018 November	73	20	93
2018 October	70	18	88
2018 September	211	17	228
2018 August	248	18	266
2018 July	169	21	190
2018 June	159	5	164
2018 May	320	19	339
2018 April	136	7	143
2018 March	155	6	161
2018 February	138	6	144
2018 January	118	6	124
2017 December	91	4	95
2017 November	115	8	123
2017 October	116	6	122
2017 September	123	20	143
2017 August	116	12	128
2017 July	174	5	179
2017 June	190	28	218
2017 May	172	21	193
2017 April	91	13	104
2017 March	238	29	267
2017 February	216	20	236
2017 January	65	5	70
2016 December	101	9	110
2016 November	166	11	177
2016 October	127	16	143
2016 September	56	10	66
2016 August	24	7	31
2016 July	0	1	1

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