Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: Radiologic–pathologic correlation of the response and disease-free survival depending on molecular subtype

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(B) Node with change in echogeneicity after intratumor injection of the radioisotope. (C) Radioisotope marking of microcalcifications through an internal stereotactic metallic marker. (D) Lymphogammagraphy (anterior projection) with masking and axillary sentinel node. (E) Location of breast lesion and sentinel lymph node and design of surgical approach. (F) Gamma-detecting portable probe model Europrobe® II. (G) Axillary incision and tracking through gamma-detecting probe at the OR. (H) Gamma-probe-guided ex vivo checking through of the activity of the extracted nodes." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Arias Ortega, M.Y. Torres Sousa, B. González García, R. Pardo García, A. González López, M. Delgado Portela" "autores" => array:6 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Arias Ortega" ] 1 => array:2 [ "nombre" => "M.Y." "apellidos" => "Torres Sousa" ] 2 => array:2 [ "nombre" => "B." 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Cruz Ciria, F. Jiménez Aragón, C. García Mur, H. Esteban Cuesta, B. Gros Bañeres" "autores" => array:5 [ 0 => array:4 [ "nombre" => "S." "apellidos" => "Cruz Ciria" "email" => array:1 [ 0 => "silviacruzciria@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "F." "apellidos" => "Jiménez Aragón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "García Mur" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "H." "apellidos" => "Esteban Cuesta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "B." "apellidos" => "Gros Bañeres" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Radiodiagnóstico, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Urgencias, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Resonancia magnética en el cáncer de mama tratado con neoadyuvancia: correlación radiopatológica de la respuesta y supervivencia libre de enfermedad en función del subtipo molecular" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 527 "Ancho" => 1301 "Tamanyo" => 83284 ] ] "descripcion" => array:1 [ "en" => "T1-weighted dynamic images on the axial view. (a) Pre-chemotherapy (pre-CT) MRI: nodular enhancement (arrow) of ovoid morphology and lobular contours with heterogenous enhancement occupying the mid and posterior views of lower quadrants of left breast with luminal B HER2− immunohistochemical profile. (b) Post-CT MRI: no response to neoadjuvant therapy. The only difference is two (2) areas of central necrosis (arrow)." ] ] ] "textoCompleto" => "IntroductionBreast cancer (BC) includes a heterogeneous group of tumors with multiple classifications commonly based on histopathological characteristics that do not always reflect the prognosis of the condition. Histologically similar tumors can have good prognosis and different therapeutic responses that can be due to its molecular profile.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Recent studies classify BC into different molecular subtypes according to the inmunohistochemical characteristics: luminal, HER2+ and triple negative (TN). The luminal subtype is characterized by expressing hormonal receptors–estrogen or progesterone receptors; subtype HER2+, by expressing the receptor 2 of the human epidermal growth factor and by the expression of negative hormonal receptors and the subtype TN by not expressing hormonal receptors or HER2. Today the luminal subtype is subdivided following the Ki67 cell proliferation rate and the HER2 expression in luminal A (HER2− and Ki67<14%), luminal B HER2− (HER2− and Ki67>14%) and luminal B HER2+ (HER2+, regardless of Ki67).<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Other than conventional chemotherapy subtypes expressing hormone receptors also benefit from hormone therapy while those expressing the human epidermal growth factor type 2 from monoclonal antibodies–therapies that have revolutionized the prognosis of BC.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>Neoadjuvant chemotherapy (NACT) has increased the rate of breast conservation surgeries. Also a complete radiological response to NACT has proven to be suggestive of disease-free survival.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>The role of MRI in BC stratification and its advantages over other diagnostic modalities to monitor the response to NACT have been confirmed in several studies.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> However, few articles study the response to NACT based on the molecular subtype.<a class="elsevierStyleCrossRefs" href="#bib0005">1,5</a>The goal of this study is to assess the radiological and pathological response in different molecular subtypes of BC, the correlation among them and analyze its implication in disease-free survival.Materials and methodsPatientsIn this retrospective study 205 patients with BC were included (211 carcinomas) treated at our institution from January 2003 to January 2012 meeting the following criteria: patients diagnosed with infiltrating BC through a thick needle biopsy with immunohistochemical analysis of the sample (hormone receptors, HER2 and Ki67) treated with NACT with pre- and post-chemotherapy MRI and further surgical therapy with anatomopathological assessment of the pathological response at the surgical piece based on Miller and Payne classification.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> All MRI studies were of enough quality to be assessed. Seventeen patients (17) were excluded whose pre-chemotherapy MRI was done in another institution. The study got the approval of the Local Ethical Committee and all participants gave their informed written consent.Definition of tumor subtypesThe sample was classified into five (5) tumor subtypes based on the immunohistochemical characteristics of BC: luminal A, luminal B HER2−, luminal B HER2+, HER2+ and TN.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>The immunohistochemical results of HER2 expression were categorized into three (3) subgroups (+, ++ and +++). The samples that did not express HER2 or with expression + were considered HER2−. The samples expressing HER2+++ were considered HER2+. In the HER2++ samples fluorescent in situ hybridization (FISH) to determine gene amplification and confirm its positivity was used.Image studies and radiological responseAll patients were included in the BC process of our center. MRI studies were done following the times established in our diagnostic protocol. Pre-chemotherapy MRI was done 15 days after the patient's enrollment in the process and NACT was started one week after MRI staging. Post-chemotherapy MRI was planned 15–21 days after the last cycle so that time elapsed until the surgical intervention would not go beyond 20 days. In all cases one Signa® HD 1.5T MRI kit was used (GE Healthcare, Milwaukee, WI, U.S.A.). Patients were studied in the decubitus prone position to minimize breathing artifacts with a specific surface antenna. The protocol used included the following sequences: T2-weighted axial fast spin echo (FSE) (TR: 4.640; TE: 90.9; ET: 13; cut thickness: 2; FOV: 32×32; matrix: 320×224), 3D T1-weighted dynamic study in fast spoiled gradient-echo [FSPGR]) (TR: 5; TE: 2.4; cut thickness: 2; FOV: 34×34; matrix: 320×224), before and, 1, 2, 3, 4, 5 and 6min after the injection of IV paramagnetic contrast, 0.15mmol/kg of Gd-DTPA at 3ml/s followed by a bolus of saline solution of 20ml, and T1-diffusion weighted SE-EPI, b=600 (TR: 8.000; TE: 61.3; cut thickness: 5; FOV: 34×34; matrix: 64×128). Postprocessing was performed using the Advantage® Windows 4.3 software (GE Healthcare, Milwaukee, WI, U.S.A.) for the acquisition of subtraction images, maximum intensity (MIP), multiplanar reconstruction, functional curves, apparent diffusion coefficient and diffusion restriction percentage. Morphological and functional criteria were assessed according to BI-RADS classification for staging purposes<a class="elsevierStyleCrossRef" href="#bib0035">7</a> without considering in this study changes in functional curves or modifications in the diffusion restriction percentage after NACT. In order to assess the radiological response to NACT both pre-chemotherapy MRI studies and post-chemotherapy MRI studies were compared by a radiologist with over 10 years of experience in breast disease. Patients were classified based on the degree of reduction of tumor size by measuring the maximum diameters of the largest lesion in subtracted MIP images. The four (4) groups of radiological response were: no response (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), minor partial response (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), major partial response (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) and complete response (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). Non-responsiveness happened when no changes at all were observed in the tumor size; minor partial response happened when the tumor sized had shrunk <50% of its maximum tumor diameter; major partial response happened when the tumor size had shrunk >50% of its maximum tumor diameter; and complete response happened in the absence of enhancement and when lesions were gone. The type of morphological response was classified into three (3) different groups: concentric reduction–when the tumor size reduction was circumferential; fragmentation (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>) when the tumor showed internal tear or segmentation; and mixed when both pattern responses were present.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia>Anatomopathological analysisThe anatomopathological analysis performed for the diagnosis of BC through 14G thick needle biopsy included: histological type, nuclear degree, Scarff-Bloom grading system and immunochemistry of hormone receptor, HER2 and Ki67.After surgery the pathological response to NACT was assessed by one anatomopathologist with over 10 years experience in breast disease using the Miller and Payne classification that distinguishes 5 degrees of local pathological response based on the reduction of invasive tumor cellularity (grade 1–no reduction of cellularity; grade 2–reduction below 30%; grade 3–reduction of cellularity between 30 and 90%; grade 4–reduction>90%; and grade 5–infiltrating carcinoma with possible carcinoma in situ too).<a class="elsevierStyleCrossRef" href="#bib0030">6</a>Follow-upAfter surgical therapy patients were followed up including one biochemical analysis every three (3) months, one first mammographic control after six (6) months after completing radiotherapy and annual controls through mammographies, one chest X-ray and one annual abdominopelvic ultrasound.Statistical analysisThe data obtained were processed using the statistical software SPSS® version 20.0.0 (SPSS, Inc. Chicago, IL, U.S.A.). One descriptive analysis of the demographic and clinical variables based on the type of tumor was performed. The characteristics of the different variables were accompanied by χ2 tests, t-tests and variance analyses. Kendall's Tau-b correlation coefficient test was used to analyze the correlation between the radiological response and the pathological response to NACT. The outcomes were considered statistically significant when p<0.05.Disease-free survival curves were estimated using the Kaplan–Meier test by comparing the different molecular subtypes and based both on the pathological and radiological responses. Both the follow-up time and the disease-free survival of each patient was determined by calculating the difference between the date of the pre-chemotherapy MR and the date of relapse or the date the study was finished (1-1-2012) in those cases with no tumor relapse. The differences among survival curves were assessed though the long rank test. For the assessment of Kaplan–Meier curves based on the radiological response two (2) groups were categorized: poor response–including non-responsive cases and minor partial responses and good response–including cases of major and complete partial response.ResultsOf a total of 211 patients the age range was between 29 and 81 years old (average: 51 years, average: 53.2±13.1). When it comes to the distribution based on histological types patients were 42 TN (1.9%), 29 HER2+ (13.7%), 38 luminal A (18%), 73 luminal B HER2– (34.6%) and 29 luminal B HER2+ (13.7%). In 181 patients (85.8%) the histological type related to ductal carcinoma, in 25 (11.8%) to lobulillar carcinoma and in 5 (2.4%) to unusual carcinoma. When it comes to loco-regional classification 70% of our sample were tumors included in the classification T2 (20–50mm), 41 were multifocal tumors (19.4%), 28 multicentric cases (13.3%) and 6 cases of bilaterallity (2.8%) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Radiological response to neoadjuvant chemotherapyThe subgroups HER2+ and TN showed a greater complete radiological response rate (62.1 and 45.2% respectively) while in subtypes luminal A, luminal B HER2− and luminal B HER2+ the complete radiological response rate to NACT was lower (7.9, 23.3 and 34.5% respectively). When it comes to the morphological pattern of response we observed that the concentric reduction pattern was the most common of all immunohistochemical subtypes (79.5%).Pathological response to neoadjuvant chemotherapyThe pathological response based on Miller and Payne classification was greater in the subtype HER2+ showing a 65.5%-complete pathological response rate. In the subtype TN the complete pathological response was 38.1%. Luminal tumors showed the lowest rate of complete pathological response (2.6% for luminal A, 8.2% for luminal B HER2− and 31% for luminal B HER2+).Radiopathological correlationThe rate of correlation between the pathological and the radiological response was significant in all types of immunohistochemical subtypes though greater in TN tumors with a Tau-b coefficient of 0.805 (p<0.01) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Disease-free survivalAs Kaplan–Meier curves show (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>) the disease-free survival time was lesser in the TN subtype (69.5±6.3 months), 95% CI: 57.1–81.9 with a statistically significant difference with respect to the other tumor subtypes (p=0.028). In HER2+ tumors disease-free survival was greater (91.9±3.3 months), 95% CI: 85.5–98.5 and in luminal A and B subtypes it ranged between 87.6±4.1 months, 95% CI: 79.8–95.6, and 85.8±5.8 months, IC 95%: 74.4–97.2. When assessing disease free survival based on the radiological response to MRI the differences were statistically significant (p=0.040) when comparing cases of poor response and good radiological response (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>). The analysis of these data based on the molecular subtype confirmed that disease-free survival was greater in cases of good radiological response except for the luminal A subtype (TN: 54.4 vs 76.9; HER2+: 78 vs 93.4; luminal A: 90.2 vs 78.1; luminal B HER2−: 83.9 vs 85.4; luminal B HER2+: 73.2 vs 84.4 months; p=0.049).<elsevierMultimedia ident="fig0030"></elsevierMultimedia>RelapsesAll through the follow-up we saw that TN tumors showed the highest relapse rate of all (33.3%), while HER2+ tumors showed the lowest rate of all (6.9%). In the subtypes luminal A and B (HER2− and HER2+) relapse rates ranged between 17% and 22%–a statistically significant difference (p=0.024). Comparing relapses based on the radiological response we observed between 2.2 and 35% more relapses in patients with poor response with respect to those showing good radiological response. The percentage of relapses was greater in cases of poor response in all molecular subtypes except for luminal A (TN: 50 vs 23.1; HER2+: 25 vs 4; luminal A: 16.7 vs 21.4; luminal B HER2−: 25 vs 20; luminal B HER2+: 33.3 vs 5.9 (p=0.002). When assessing relapses based on the pathological response 11.8% of the patients with complete pathological response (G5 in the Miller and Payne classification) showed relapse. In TN tumors some 71.4% of relapse patients did not show complete pathological response to NACT.DiscussionIn our study subtypes HER2+ and TN showed the highest rate of radiological response and complete pathological response. The rate of radiopathological correlation was significant in all immunohistochemical subtypes. Disease-free survival was greater in the HER2+ subtype–that by the way also showed the lowest rate of relapse and lower in the TN subtype–showing the highest relapse rate. Statistically significant differences could be seen in disease free survival when comparing cases of poor response and good radiological response to MRIs.The immunohistochemical classification has revolutionized the management of BC with specific therapies aimed at improving both the tumor response to NACT and the rate of conservative surgery.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Several task forces have been able to confirm that a good response to NACT is a favorable prognostic factor and is associated with a greater disease free survival.<a class="elsevierStyleCrossRefs" href="#bib0045">9,10</a> MRIs are an excellent tool for the in vivo assessment of tumor chemosensitivity which allows us to guide prognosis.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>The good chemosensitivity of TN tumors seen in our study–45.2% of radiological response and 38.1% of the complete pathological response matches the results of the study from Marcos de Paz et al.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> that show 84.6% good responses (complete and major partial) in the TN subtype. However in the case of chemosensitivity of the HER2+ subtype our results are different since we obtained a high rate of both radiological and complete pathological responses (62.1 and 65.5%) while in their study the HER2+ subtype showed the lowest rate of good responses (69.2%). These differences may be explained by the proportion of HER2+ tumors shown in our study–13.7 vs 20% in Marcos de Paz et al.’s study.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>Former studies showed that patients with complete pathological response to NACT have a favorable evolution and most remain disease free; however, patients with partial pathological response show greater relapse rates.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> In our study we obtained similar results–only 11.8% of the patients with complete pathological response (G5) relapsed. The radiopathological correlation was significant in all subtypes–greater in TN and HER2+ tumors and consistent with what other authors claim.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>When it comes to survival, the HER2+ subtype showed the greatest disease free survival and one relapse rate lower than the remaining molecular subtypes. On the contrary the lowest disease free survival rate of all was reported in TN tumors–mainly in cases of poor radiological response to NACT. TN tumors also showed the highest relapse rate of all. The low disease free survival and the high relapse rate of TN tumors contrasts with its high chemosensitivity. Some authors analyzed this phenomenon known as the TN paradox based on a worse prognosis based on incomplete responses.<a class="elsevierStyleCrossRefs" href="#bib0055">11,12</a> In our study the greater relapses happened in cases that did not show complete pathological response to NACT.Finally when comparing the disease free survival globally in the groups of good and poor radiological response we saw that survival was greater in the group of good response. After repeating the analysis in the different molecular subtypes the trend was kept with the exception of the luminal A subtype. Here data were not conclusive due to the few cases with complete response. This piece of information coincides with what we observed in former studies showing that the luminal A subtype is less chemosensitive.<a class="elsevierStyleCrossRef" href="#bib0065">13</a>Yet despite the elevated number of cases and follow-up time of patients our study has various limitations. In the first place to assess the degree of response to NACT in the MRI we only considered a reduction in the volume of the largest lesion of all in the MIP images of subtracted images. Other variables like enhancement variations associated with lesions or changes in the curve type were not included. However, the size change in the main lesion is the central feature used by the main generic scores of tumor response to CT–it is also the MR parameter with the greatest predictive capacity of response.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Another limitation is the heterogeneity in the courses of NACT. In order to limit this confounding variable we confirmed that no lines of therapy were highly superior in any subtypes. Other studies confirmed various lines of NACT in different molecular subtypes obtaining valid results with an analysis similar to ours.<a class="elsevierStyleCrossRefs" href="#bib0075">15,16</a> Finally we classified our sample into molecular subtypes through immunohistochemical methods instead of using more precise modalities like sub-typification based on the mRNA expression (microarray analysis). Yet despite the fact that before this classification was considered a limitation the international consensus of experts held in St. Gallen in 2011 claimed that the immunohistochemical analysis is an adequate alternative to microarray analysis.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> In the future it will be interesting to follow this line of work by analyzing tumor functional changes (enhancement analysis, intensity relation curves in time and apparent diffusion coefficient) after neoadjuvant therapy and its prognostic implication.In sum we proved the existence of a good correlation between the radiological and the pathological responses in all tumor subtypes–above all in TN and HER2+ tumors also showing greater chemosensitivity. Disease-free survival was greater in the HER2+ subtype and lower in the TN subtype. When comparing the cases of good and poor radiological response through MRI we were able to see statistically significant differences in disease-free survival.These results outline MRIs as an important tool that gives us information on the evolution of BCs treated with neoadjuvancy and that is variable based on the immunohistochemical subtype.Authors<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Manager of the integrity of the study: SCC, FJA and CGM</li><li class="elsevierStyleListItem" id="lsti0010">2.Original Idea of the Study: SCC, FJA and CGM</li><li class="elsevierStyleListItem" id="lsti0015">3.Study Design: SCC, FJA and CGM</li><li class="elsevierStyleListItem" id="lsti0020">4.Data Mining: SCC, FJA and CGM</li><li class="elsevierStyleListItem" id="lsti0025">5.Data Analysis and Interpretation: SCC, FJA, CGM, HEC and BGB</li><li class="elsevierStyleListItem" id="lsti0030">6.Statistical Analysis: BGB</li><li class="elsevierStyleListItem" id="lsti0035">7.Reference Search: SCC, FJA, CGM and HEC</li><li class="elsevierStyleListItem" id="lsti0040">8.Writing: SCC, FJA, CGM, HEC and BGB</li><li class="elsevierStyleListItem" id="lsti0045">9.Manuscript critical review with intellectually relevant contributions: SCC, FJA, CGM and HEC</li><li class="elsevierStyleListItem" id="lsti0050">10.Final Version Approval: SCC, FJA, CGM, HEC and BGB</li></ul>Ethical responsibilitiesProtection of human and animal subjectsAuthors confirm that no experiments have been performed on human beings or animals.Confidentiality of dataAuthors confirm that the protocols of their centers have been followed on matters concerning the publishing of data from patients. They also confirm that all patients included in this study have been given enough information and handed over their written informed consent for their participation in this study.Right to privacy and informed consentAuthors confirm that in this report there are no personal data of patients.Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:2 [ "identificador" => "xres389411" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objectives" 2 => "Materials and methods" 3 => "Results" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec367700" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres389412" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivos" 2 => "Material y métodos" 3 => "Resultados" 4 => "Conclusión" ] ] 3 => array:2 [ "identificador" => "xpalclavsec367701" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Definition of tumor subtypes" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Image studies and radiological response" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Anatomopathological analysis" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Follow-up" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Radiological response to neoadjuvant chemotherapy" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Pathological response to neoadjuvant chemotherapy" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Radiopathological correlation" ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "Disease-free survival" ] 4 => array:2 [ "identificador" => "sec0070" "titulo" => "Relapses" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Authors" ] 9 => array:3 [ "identificador" => "sec0085" "titulo" => "Ethical responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0090" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0095" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0100" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0140" "titulo" => "Conflict of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-06-20" "fechaAceptado" => "2012-10-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec367700" "palabras" => array:6 [ 0 => "Breast cancer" 1 => "Molecular subtypes" 2 => "Magnetic resonance imaging" 3 => "Radiologic response" 4 => "Neoadjuvant chemotherapy" 5 => "Survival" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec367701" "palabras" => array:6 [ 0 => "Cáncer de mama" 1 => "Subtipos moleculares" 2 => "Imagen por resonancia magnética" 3 => "Respuesta radiológica" 4 => "Quimioterapia neoadyuvante" 5 => "Supervivencia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "ObjectivesTo evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. Materials and methodsWe included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2−, and luminal B HER2+), we used the χ2 test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic–pathologic correlation, and the disease-free survival. ResultsThe subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2− subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic–pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (p=0.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. ConclusionMRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "ObjetivosValorar la respuesta radiológica, patológica y su correlación en los subtipos moleculares del cáncer de mama y analizar su implicación en la supervivencia libre de enfermedad. Material y métodosSe incluyeron 205 pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante. Se valoró la respuesta radiológica con RM pre y posquimioterapia. La respuesta patológica se clasificó según la escala de Miller y Payne. Se valoró la respuesta radiológica y patológica en cada subtipo (HER2+, TN, luminal A, luminal B HER2– y luminal B HER2+), la correlación radiopatológica y la supervivencia libre de enfermedad mediante las pruebas χ2, t de Student, ANOVA y Tau-b de Kendall. ResultadosLos subtipos HER2+ (62,1%) y TN (45,2%) mostraron mayor tasa de respuesta radiológica completa. La respuesta patológica fue del 65,5% en el HER2+, 38,1% en el TN, 2,6% en los luminales A, 8,2% en los luminales B HER2– y 31% en los luminales B HER2+. El índice de correlación radiopatológico fue significativo en todos los subtipos, mayor en los TN y HER2 (coeficientes Tau-b 0,805 y 0,717 respectivamente). La supervivencia libre de enfermedad fue mayor para HER2+ (91,9±3,3 meses) y menor en el TN (69,5±6,3 meses), con diferencias significativas entre los casos de mala y buena respuesta radiológica (p=0,040). La supervivencia fue superior en los casos de buena respuesta radiológica a excepción del subtipo luminal A. ConclusiónLa RM puede ser una herramienta que aporta información de la evolución del CM tratado con neoadyuvancia, variable según el subtipo inmunohistoquímico." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Cruz Ciria S, Jiménez Aragón F, García Mur C, Esteban Cuesta H, Gros Bañeres B. Resonancia magnética en el cáncer de mama tratado con neoadyuvancia: correlación radiopatológica de la respuesta y supervivencia libre de enfermedad en función del subtipo molecular. Radiología. 2014;56:524–532." ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 527 "Ancho" => 1301 "Tamanyo" => 83284 ] ] "descripcion" => array:1 [ "en" => "T1-weighted dynamic images on the axial view. (a) Pre-chemotherapy (pre-CT) MRI: nodular enhancement (arrow) of ovoid morphology and lobular contours with heterogenous enhancement occupying the mid and posterior views of lower quadrants of left breast with luminal B HER2− immunohistochemical profile. (b) Post-CT MRI: no response to neoadjuvant therapy. The only difference is two (2) areas of central necrosis (arrow)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 533 "Ancho" => 1301 "Tamanyo" => 73667 ] ] "descripcion" => array:1 [ "en" => "Axial MIP images with subtracted images. (a) Pre-CT MRI: homogeneous nodular enhancement (arrow) of a defined contour located in the anterior view of the external quadrants of right breast with luminal B HER2+ immunohistochemical profile. (b) Post-CT MRI: minor partial response with a pattern of concentric reduction (arrow) after neoadjuvant therapy." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 615 "Ancho" => 1301 "Tamanyo" => 104293 ] ] "descripcion" => array:1 [ "en" => "Axial MIP images with subtracted images. (a) Pre-CT MRI: annular nodular enhancement (arrow) and retroareolar lobulated contrast with TN immunohistochemical profile. (b) Post-CT MRI: major partial response with a pattern of concentric reduction (arrow) after neoadjuvant therapy." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 616 "Ancho" => 1301 "Tamanyo" => 81890 ] ] "descripcion" => array:1 [ "en" => "Axial MIP images with subtracted images. (a) Pre-CT MRI: diffused non-nodular glandular enhancement (arrow) occupying the three (3) breast views (arrows) with HER2+ immunohistochemical profile. (b) Post-CT MRI: complete radiological response with no contrast agent (asterisk) after neoadjuvant therapy." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 617 "Ancho" => 1301 "Tamanyo" => 75420 ] ] "descripcion" => array:1 [ "en" => "(a) Pre-CT MRI: heterogeneous regional enhancement located in the anterior mid view of upper quadrants with luminal B HER2+ immunohistochemical profile. (b) Post-CT MRI: minor partial response after neoadjuvant therapy with morphological pattern of tumor fragmentation (asterisk)." ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1107 "Ancho" => 2372 "Tamanyo" => 148741 ] ] "descripcion" => array:1 [ "en" => "Kaplan–Meier curves of disease-free survival: (a) based on different molecular subtypes; (b) based on the radiological response in the MRI to NACT (good radiological response: complete response and major partial response, poor radiological response: minor partial response and no response at all)." ] ] 6 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "ND, nuclear degree; CT, chemotherapy; SB, Scarff-Bloom." "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">TN (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">HER 2+ (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Luminal A (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Luminal B HER2− (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Luminal B HER2+ (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Valor p \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Number \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 (19.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (13.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 (34.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (13.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51.5±13.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.3±12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55.7±15.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.5±13.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.1±11.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p=0.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Histological type</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ductal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (88.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 (79) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (79.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (93) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p=0.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lobulillar \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (17.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (4.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Size pre-CT</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T1 (<2 cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p=0.32 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T2 (2–5cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (86.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47 (65.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (70.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T3 (>5cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (28.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (10.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (26) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SB</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p<0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4–6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (27.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (83.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49 (68.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (51.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7–9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (72.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (13.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (30.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (48.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (24.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (18.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p<0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (48.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 (70.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45 (62.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (65.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (58.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (51.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (19.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (34.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Solitary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (66.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (72.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (76.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 (57.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (55.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p=0.154 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multifocal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (17.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (10.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (21.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (27.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multicentric \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (14.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (10.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (13.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (12.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (17.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bilateral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (8.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab599935.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Descriptive analysis by molecular subtype." ] ] 7 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "PR: pathological response; RR: radiological response; DFS: disease-free survival." "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">TN (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">HER 2+ (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Luminal A (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Luminal B HER2−(%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Luminal B HER2+ (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Significance \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Number of cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 (19.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (13.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 (34.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (13.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complete RR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (45.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (62.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (7.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (23.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (34.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p<0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complete PR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (38.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (65.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (8.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p<0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Radiopathological correlation (Kendall's Tau-b) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.805 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.717 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.709 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.606 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.554 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Relapses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (6.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (18.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (21.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (17.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p=0.099 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFS (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69.5±6.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">91.9±3.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87.6±4.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87.5±3.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85.8±5.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p=0.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab599936.png" ] ] 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Resonancia magnética en el cáncer de mama tratado con neoadyuvancia: correlación radiopatológica de la respuesta y supervivencia libre de enfermedad en función del subtipo molecular

S. Cruz Ciriaa,

Corresponding author

silviacruzciria@gmail.com

Corresponding author.

, F. Jiménez Aragóna, C. García Mura, H. Esteban Cuestaa, B. Gros Bañeresb

a Servicio de Radiodiagnóstico, Hospital Universitario Miguel Servet, Zaragoza, Spain

b Servicio de Urgencias, Hospital Universitario Miguel Servet, Zaragoza, Spain

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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">T1-weighted dynamic images on the axial view&#46; &#40;a&#41; Pre-chemotherapy &#40;pre-CT&#41; MRI&#58; nodular enhancement &#40;arrow&#41; of ovoid morphology and lobular contours with heterogenous enhancement occupying the mid and posterior views of lower quadrants of left breast with luminal B HER2&#8722; immunohistochemical profile&#46; &#40;b&#41; Post-CT MRI&#58; no response to neoadjuvant therapy&#46; The only difference is two &#40;2&#41; areas of central necrosis &#40;arrow&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Breast cancer &#40;BC&#41; includes a heterogeneous group of tumors with multiple classifications commonly based on histopathological characteristics that do not always reflect the prognosis of the condition&#46; Histologically similar tumors can have good prognosis and different therapeutic responses that can be due to its molecular profile&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Recent studies classify BC into different molecular subtypes according to the inmunohistochemical characteristics&#58; luminal&#44; HER2&#43; and triple negative &#40;TN&#41;&#46; The luminal subtype is characterized by expressing hormonal receptors&#8211;estrogen or progesterone receptors&#59; subtype HER2&#43;&#44; by expressing the receptor 2 of the human epidermal growth factor and by the expression of negative hormonal receptors and the subtype TN by not expressing hormonal receptors or HER2&#46; Today the luminal subtype is subdivided following the Ki67 cell proliferation rate and the HER2 expression in luminal A &#40;HER2&#8722; and Ki67<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>14&#37;&#41;&#44; luminal B HER2&#8722; &#40;HER2&#8722; and Ki67<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>14&#37;&#41; and luminal B HER2&#43; &#40;HER2&#43;&#44; regardless of Ki67&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Other than conventional chemotherapy subtypes expressing hormone receptors also benefit from hormone therapy while those expressing the human epidermal growth factor type 2 from monoclonal antibodies&#8211;therapies that have revolutionized the prognosis of BC&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Neoadjuvant chemotherapy &#40;NACT&#41; has increased the rate of breast conservation surgeries&#46; Also a complete radiological response to NACT has proven to be suggestive of disease-free survival&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The role of MRI in BC stratification and its advantages over other diagnostic modalities to monitor the response to NACT have been confirmed in several studies&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However&#44; few articles study the response to NACT based on the molecular subtype&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The goal of this study is to assess the radiological and pathological response in different molecular subtypes of BC&#44; the correlation among them and analyze its implication in disease-free survival&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0025" class="elsevierStylePara elsevierViewall">In this retrospective study 205 patients with BC were included &#40;211 carcinomas&#41; treated at our institution from January 2003 to January 2012 meeting the following criteria&#58; patients diagnosed with infiltrating BC through a thick needle biopsy with immunohistochemical analysis of the sample &#40;hormone receptors&#44; HER2 and Ki67&#41; treated with NACT with pre- and post-chemotherapy MRI and further surgical therapy with anatomopathological assessment of the pathological response at the surgical piece based on Miller and Payne classification&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> All MRI studies were of enough quality to be assessed&#46; Seventeen patients &#40;17&#41; were excluded whose pre-chemotherapy MRI was done in another institution&#46; The study got the approval of the Local Ethical Committee and all participants gave their informed written consent&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Definition of tumor subtypes</span><p id="par0030" class="elsevierStylePara elsevierViewall">The sample was classified into five &#40;5&#41; tumor subtypes based on the immunohistochemical characteristics of BC&#58; luminal A&#44; luminal B HER2&#8722;&#44; luminal B HER2&#43;&#44; HER2&#43; and TN&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The immunohistochemical results of HER2 expression were categorized into three &#40;3&#41; subgroups &#40;&#43;&#44; &#43;&#43; and &#43;&#43;&#43;&#41;&#46; The samples that did not express HER2 or with expression &#43; were considered HER2&#8722;&#46; The samples expressing HER2&#43;&#43;&#43; were considered HER2&#43;&#46; In the HER2&#43;&#43; samples fluorescent in situ hybridization &#40;FISH&#41; to determine gene amplification and confirm its positivity was used&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Image studies and radiological response</span><p id="par0040" class="elsevierStylePara elsevierViewall">All patients were included in the BC process of our center&#46; MRI studies were done following the times established in our diagnostic protocol&#46; Pre-chemotherapy MRI was done 15 days after the patient&#39;s enrollment in the process and NACT was started one week after MRI staging&#46; Post-chemotherapy MRI was planned 15&#8211;21 days after the last cycle so that time elapsed until the surgical intervention would not go beyond 20 days&#46; In all cases one Signa<span class="elsevierStyleSup">&#174;</span> HD 1&#46;5<span class="elsevierStyleHsp" style=""></span>T MRI kit was used &#40;GE Healthcare&#44; Milwaukee&#44; WI&#44; U&#46;S&#46;A&#46;&#41;&#46; Patients were studied in the decubitus prone position to minimize breathing artifacts with a specific surface antenna&#46; The protocol used included the following sequences&#58; T2-weighted axial fast spin echo &#40;FSE&#41; &#40;TR&#58; 4&#46;640&#59; TE&#58; 90&#46;9&#59; ET&#58; 13&#59; cut thickness&#58; 2&#59; FOV&#58; 32<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>32&#59; matrix&#58; 320<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>224&#41;&#44; 3D T1-weighted dynamic study in fast spoiled gradient-echo &#91;FSPGR&#93;&#41; &#40;TR&#58; 5&#59; TE&#58; 2&#46;4&#59; cut thickness&#58; 2&#59; FOV&#58; 34<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>34&#59; matrix&#58; 320<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>224&#41;&#44; before and&#44; 1&#44; 2&#44; 3&#44; 4&#44; 5 and 6<span class="elsevierStyleHsp" style=""></span>min after the injection of IV paramagnetic contrast&#44; 0&#46;15<span class="elsevierStyleHsp" style=""></span>mmol&#47;kg of Gd-DTPA at 3<span class="elsevierStyleHsp" style=""></span>ml&#47;s followed by a bolus of saline solution of 20<span class="elsevierStyleHsp" style=""></span>ml&#44; and T1-diffusion weighted SE-EPI&#44; <span class="elsevierStyleItalic">b</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>600 &#40;TR&#58; 8&#46;000&#59; TE&#58; 61&#46;3&#59; cut thickness&#58; 5&#59; FOV&#58; 34<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>34&#59; matrix&#58; 64<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>128&#41;&#46; Postprocessing was performed using the Advantage<span class="elsevierStyleSup">&#174;</span> Windows 4&#46;3 software &#40;GE Healthcare&#44; Milwaukee&#44; WI&#44; U&#46;S&#46;A&#46;&#41; for the acquisition of subtraction images&#44; maximum intensity &#40;MIP&#41;&#44; multiplanar reconstruction&#44; functional curves&#44; apparent diffusion coefficient and diffusion restriction percentage&#46; Morphological and functional criteria were assessed according to BI-RADS classification for staging purposes<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> without considering in this study changes in functional curves or modifications in the diffusion restriction percentage after NACT&#46; In order to assess the radiological response to NACT both pre-chemotherapy MRI studies and post-chemotherapy MRI studies were compared by a radiologist with over 10 years of experience in breast disease&#46; Patients were classified based on the degree of reduction of tumor size by measuring the maximum diameters of the largest lesion in subtracted MIP images&#46; The four &#40;4&#41; groups of radiological response were&#58; no response &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; minor partial response &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; major partial response &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; and complete response &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; Non-responsiveness happened when no changes at all were observed in the tumor size&#59; minor partial response happened when the tumor sized had shrunk &#60;50&#37; of its maximum tumor diameter&#59; major partial response happened when the tumor size had shrunk &#62;50&#37; of its maximum tumor diameter&#59; and complete response happened in the absence of enhancement and when lesions were gone&#46; The type of morphological response was classified into three &#40;3&#41; different groups&#58; concentric reduction&#8211;when the tumor size reduction was circumferential&#59; fragmentation &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41; when the tumor showed internal tear or segmentation&#59; and mixed when both pattern responses were present&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Anatomopathological analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">The anatomopathological analysis performed for the diagnosis of BC through 14<span class="elsevierStyleHsp" style=""></span>G thick needle biopsy included&#58; histological type&#44; nuclear degree&#44; Scarff-Bloom grading system and immunochemistry of hormone receptor&#44; HER2 and Ki67&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">After surgery the pathological response to NACT was assessed by one anatomopathologist with over 10 years experience in breast disease using the Miller and Payne classification that distinguishes 5 degrees of local pathological response based on the reduction of invasive tumor cellularity &#40;grade 1&#8211;no reduction of cellularity&#59; grade 2&#8211;reduction below 30&#37;&#59; grade 3&#8211;reduction of cellularity between 30 and 90&#37;&#59; grade 4&#8211;reduction<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>90&#37;&#59; and grade 5&#8211;infiltrating carcinoma with possible carcinoma in situ too&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Follow-up</span><p id="par0055" class="elsevierStylePara elsevierViewall">After surgical therapy patients were followed up including one biochemical analysis every three &#40;3&#41; months&#44; one first mammographic control after six &#40;6&#41; months after completing radiotherapy and annual controls through mammographies&#44; one chest X-ray and one annual abdominopelvic ultrasound&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">The data obtained were processed using the statistical software SPSS<span class="elsevierStyleSup">&#174;</span> version 20&#46;0&#46;0 &#40;SPSS&#44; Inc&#46; Chicago&#44; IL&#44; U&#46;S&#46;A&#46;&#41;&#46; One descriptive analysis of the demographic and clinical variables based on the type of tumor was performed&#46; The characteristics of the different variables were accompanied by <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> tests&#44; <span class="elsevierStyleItalic">t</span>-tests and variance analyses&#46; Kendall&#39;s Tau-b correlation coefficient test was used to analyze the correlation between the radiological response and the pathological response to NACT&#46; The outcomes were considered statistically significant when <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Disease-free survival curves were estimated using the Kaplan&#8211;Meier test by comparing the different molecular subtypes and based both on the pathological and radiological responses&#46; Both the follow-up time and the disease-free survival of each patient was determined by calculating the difference between the date of the pre-chemotherapy MR and the date of relapse or the date the study was finished &#40;1-1-2012&#41; in those cases with no tumor relapse&#46; The differences among survival curves were assessed though the long rank test&#46; For the assessment of Kaplan&#8211;Meier curves based on the radiological response two &#40;2&#41; groups were categorized&#58; poor response&#8211;including non-responsive cases and minor partial responses and good response&#8211;including cases of major and complete partial response&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Of a total of 211 patients the age range was between 29 and 81 years old &#40;average&#58; 51 years&#44; average&#58; 53&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;1&#41;&#46; When it comes to the distribution based on histological types patients were 42 TN &#40;1&#46;9&#37;&#41;&#44; 29 HER2&#43; &#40;13&#46;7&#37;&#41;&#44; 38 luminal A &#40;18&#37;&#41;&#44; 73 luminal B HER2&#8211; &#40;34&#46;6&#37;&#41; and 29 luminal B HER2&#43; &#40;13&#46;7&#37;&#41;&#46; In 181 patients &#40;85&#46;8&#37;&#41; the histological type related to ductal carcinoma&#44; in 25 &#40;11&#46;8&#37;&#41; to lobulillar carcinoma and in 5 &#40;2&#46;4&#37;&#41; to unusual carcinoma&#46; When it comes to loco-regional classification 70&#37; of our sample were tumors included in the classification T2 &#40;20&#8211;50<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; 41 were multifocal tumors &#40;19&#46;4&#37;&#41;&#44; 28 multicentric cases &#40;13&#46;3&#37;&#41; and 6 cases of bilaterallity &#40;2&#46;8&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Radiological response to neoadjuvant chemotherapy</span><p id="par0075" class="elsevierStylePara elsevierViewall">The subgroups HER2&#43; and TN showed a greater complete radiological response rate &#40;62&#46;1 and 45&#46;2&#37; respectively&#41; while in subtypes luminal A&#44; luminal B HER2&#8722; and luminal B HER2&#43; the complete radiological response rate to NACT was lower &#40;7&#46;9&#44; 23&#46;3 and 34&#46;5&#37; respectively&#41;&#46; When it comes to the morphological pattern of response we observed that the concentric reduction pattern was the most common of all immunohistochemical subtypes &#40;79&#46;5&#37;&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Pathological response to neoadjuvant chemotherapy</span><p id="par0080" class="elsevierStylePara elsevierViewall">The pathological response based on Miller and Payne classification was greater in the subtype HER2&#43; showing a 65&#46;5&#37;-complete pathological response rate&#46; In the subtype TN the complete pathological response was 38&#46;1&#37;&#46; Luminal tumors showed the lowest rate of complete pathological response &#40;2&#46;6&#37; for luminal A&#44; 8&#46;2&#37; for luminal B HER2&#8722; and 31&#37; for luminal B HER2&#43;&#41;&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Radiopathological correlation</span><p id="par0085" class="elsevierStylePara elsevierViewall">The rate of correlation between the pathological and the radiological response was significant in all types of immunohistochemical subtypes though greater in TN tumors with a Tau-b coefficient of 0&#46;805 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Disease-free survival</span><p id="par0090" class="elsevierStylePara elsevierViewall">As Kaplan&#8211;Meier curves show &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41; the disease-free survival time was lesser in the TN subtype &#40;69&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;3 months&#41;&#44; 95&#37; CI&#58; 57&#46;1&#8211;81&#46;9 with a statistically significant difference with respect to the other tumor subtypes &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;028&#41;&#46; In HER2&#43; tumors disease-free survival was greater &#40;91&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3 months&#41;&#44; 95&#37; CI&#58; 85&#46;5&#8211;98&#46;5 and in luminal A and B subtypes it ranged between 87&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;1 months&#44; 95&#37; CI&#58; 79&#46;8&#8211;95&#46;6&#44; and 85&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;8 months&#44; IC 95&#37;&#58; 74&#46;4&#8211;97&#46;2&#46; When assessing disease free survival based on the radiological response to MRI the differences were statistically significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;040&#41; when comparing cases of poor response and good radiological response &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46; The analysis of these data based on the molecular subtype confirmed that disease-free survival was greater in cases of good radiological response except for the luminal A subtype &#40;TN&#58; 54&#46;4 vs 76&#46;9&#59; HER2&#43;&#58; 78 vs 93&#46;4&#59; luminal A&#58; 90&#46;2 vs 78&#46;1&#59; luminal B HER2&#8722;&#58; 83&#46;9 vs 85&#46;4&#59; luminal B HER2&#43;&#58; 73&#46;2 vs 84&#46;4 months&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;049&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Relapses</span><p id="par0095" class="elsevierStylePara elsevierViewall">All through the follow-up we saw that TN tumors showed the highest relapse rate of all &#40;33&#46;3&#37;&#41;&#44; while HER2&#43; tumors showed the lowest rate of all &#40;6&#46;9&#37;&#41;&#46; In the subtypes luminal A and B &#40;HER2&#8722; and HER2&#43;&#41; relapse rates ranged between 17&#37; and 22&#37;&#8211;a statistically significant difference &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41;&#46; Comparing relapses based on the radiological response we observed between 2&#46;2 and 35&#37; more relapses in patients with poor response with respect to those showing good radiological response&#46; The percentage of relapses was greater in cases of poor response in all molecular subtypes except for luminal A &#40;TN&#58; 50 vs 23&#46;1&#59; HER2&#43;&#58; 25 vs 4&#59; luminal A&#58; 16&#46;7 vs 21&#46;4&#59; luminal B HER2&#8722;&#58; 25 vs 20&#59; luminal B HER2&#43;&#58; 33&#46;3 vs 5&#46;9 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46; When assessing relapses based on the pathological response 11&#46;8&#37; of the patients with complete pathological response &#40;G5 in the Miller and Payne classification&#41; showed relapse&#46; In TN tumors some 71&#46;4&#37; of relapse patients did not show complete pathological response to NACT&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">In our study subtypes HER2&#43; and TN showed the highest rate of radiological response and complete pathological response&#46; The rate of radiopathological correlation was significant in all immunohistochemical subtypes&#46; Disease-free survival was greater in the HER2&#43; subtype&#8211;that by the way also showed the lowest rate of relapse and lower in the TN subtype&#8211;showing the highest relapse rate&#46; Statistically significant differences could be seen in disease free survival when comparing cases of poor response and good radiological response to MRIs&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The immunohistochemical classification has revolutionized the management of BC with specific therapies aimed at improving both the tumor response to NACT and the rate of conservative surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Several task forces have been able to confirm that a good response to NACT is a favorable prognostic factor and is associated with a greater disease free survival&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> MRIs are an excellent tool for the in vivo assessment of tumor chemosensitivity which allows us to guide prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The good chemosensitivity of TN tumors seen in our study&#8211;45&#46;2&#37; of radiological response and 38&#46;1&#37; of the complete pathological response matches the results of the study from Marcos de Paz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> that show 84&#46;6&#37; good responses &#40;complete and major partial&#41; in the TN subtype&#46; However in the case of chemosensitivity of the HER2&#43; subtype our results are different since we obtained a high rate of both radiological and complete pathological responses &#40;62&#46;1 and 65&#46;5&#37;&#41; while in their study the HER2&#43; subtype showed the lowest rate of good responses &#40;69&#46;2&#37;&#41;&#46; These differences may be explained by the proportion of HER2&#43; tumors shown in our study&#8211;13&#46;7 vs 20&#37; in Marcos de Paz et al&#46;&#8217;s study&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Former studies showed that patients with complete pathological response to NACT have a favorable evolution and most remain disease free&#59; however&#44; patients with partial pathological response show greater relapse rates&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In our study we obtained similar results&#8211;only 11&#46;8&#37; of the patients with complete pathological response &#40;G5&#41; relapsed&#46; The radiopathological correlation was significant in all subtypes&#8211;greater in TN and HER2&#43; tumors and consistent with what other authors claim&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">When it comes to survival&#44; the HER2&#43; subtype showed the greatest disease free survival and one relapse rate lower than the remaining molecular subtypes&#46; On the contrary the lowest disease free survival rate of all was reported in TN tumors&#8211;mainly in cases of poor radiological response to NACT&#46; TN tumors also showed the highest relapse rate of all&#46; The low disease free survival and the high relapse rate of TN tumors contrasts with its high chemosensitivity&#46; Some authors analyzed this phenomenon known as the TN paradox based on a worse prognosis based on incomplete responses&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a> In our study the greater relapses happened in cases that did not show complete pathological response to NACT&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Finally when comparing the disease free survival globally in the groups of good and poor radiological response we saw that survival was greater in the group of good response&#46; After repeating the analysis in the different molecular subtypes the trend was kept with the exception of the luminal A subtype&#46; Here data were not conclusive due to the few cases with complete response&#46; This piece of information coincides with what we observed in former studies showing that the luminal A subtype is less chemosensitive&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Yet despite the elevated number of cases and follow-up time of patients our study has various limitations&#46; In the first place to assess the degree of response to NACT in the MRI we only considered a reduction in the volume of the largest lesion of all in the MIP images of subtracted images&#46; Other variables like enhancement variations associated with lesions or changes in the curve type were not included&#46; However&#44; the size change in the main lesion is the central feature used by the main generic scores of tumor response to CT&#8211;it is also the MR parameter with the greatest predictive capacity of response&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Another limitation is the heterogeneity in the courses of NACT&#46; In order to limit this confounding variable we confirmed that no lines of therapy were highly superior in any subtypes&#46; Other studies confirmed various lines of NACT in different molecular subtypes obtaining valid results with an analysis similar to ours&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> Finally we classified our sample into molecular subtypes through immunohistochemical methods instead of using more precise modalities like sub-typification based on the mRNA expression &#40;microarray analysis&#41;&#46; Yet despite the fact that before this classification was considered a limitation the international consensus of experts held in St&#46; Gallen in 2011 claimed that the immunohistochemical analysis is an adequate alternative to microarray analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In the future it will be interesting to follow this line of work by analyzing tumor functional changes &#40;enhancement analysis&#44; intensity relation curves in time and apparent diffusion coefficient&#41; after neoadjuvant therapy and its prognostic implication&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In sum we proved the existence of a good correlation between the radiological and the pathological responses in all tumor subtypes&#8211;above all in TN and HER2&#43; tumors also showing greater chemosensitivity&#46; Disease-free survival was greater in the HER2&#43; subtype and lower in the TN subtype&#46; When comparing the cases of good and poor radiological response through MRI we were able to see statistically significant differences in disease-free survival&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">These results outline MRIs as an important tool that gives us information on the evolution of BCs treated with neoadjuvancy and that is variable based on the immunohistochemical subtype&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Authors</span><p id="par0160" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Manager of the integrity of the study&#58; SCC&#44; FJA and CGM</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0170" class="elsevierStylePara elsevierViewall">Original Idea of the Study&#58; SCC&#44; FJA and CGM</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0175" class="elsevierStylePara elsevierViewall">Study Design&#58; SCC&#44; FJA and CGM</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0180" class="elsevierStylePara elsevierViewall">Data Mining&#58; SCC&#44; FJA and CGM</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Data Analysis and Interpretation&#58; SCC&#44; FJA&#44; CGM&#44; HEC and BGB</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#46;</span><p id="par0190" class="elsevierStylePara elsevierViewall">Statistical Analysis&#58; BGB</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">7&#46;</span><p id="par0195" class="elsevierStylePara elsevierViewall">Reference Search&#58; SCC&#44; FJA&#44; CGM and HEC</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">8&#46;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Writing&#58; SCC&#44; FJA&#44; CGM&#44; HEC and BGB</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">9&#46;</span><p id="par0205" class="elsevierStylePara elsevierViewall">Manuscript critical review with intellectually relevant contributions&#58; SCC&#44; FJA&#44; CGM and HEC</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">10&#46;</span><p id="par0210" class="elsevierStylePara elsevierViewall">Final Version Approval&#58; SCC&#44; FJA&#44; CGM&#44; HEC and BGB</p></li></ul></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Ethical responsibilities</span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Protection of human and animal subjects</span><p id="par0215" class="elsevierStylePara elsevierViewall">Authors confirm that no experiments have been performed on human beings or animals&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Confidentiality of data</span><p id="par0145" class="elsevierStylePara elsevierViewall">Authors confirm that the protocols of their centers have been followed on matters concerning the publishing of data from patients&#46; They also confirm that all patients included in this study have been given enough information and handed over their written informed consent for their participation in this study&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Right to privacy and informed consent</span><p id="par0150" class="elsevierStylePara elsevierViewall">Authors confirm that in this report there are no personal data of patients&#46;</p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conflict of interest</span><p id="par0305" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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            0 => "Resumen"
            1 => "Objetivos"
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            3 => "Resultados"
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        4 => array:2 [
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          "titulo" => "Introduction"
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        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patients"
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            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Definition of tumor subtypes"
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            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Image studies and radiological response"
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            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Anatomopathological analysis"
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            4 => array:2 [
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              "titulo" => "Follow-up"
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          "titulo" => "Results"
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            0 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Radiological response to neoadjuvant chemotherapy"
            ]
            1 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Pathological response to neoadjuvant chemotherapy"
            ]
            2 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Radiopathological correlation"
            ]
            3 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Disease-free survival"
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            4 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Relapses"
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          "titulo" => "Discussion"
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          "titulo" => "Authors"
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          "titulo" => "Ethical responsibilities"
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              "identificador" => "sec0090"
              "titulo" => "Protection of human and animal subjects"
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            1 => array:2 [
              "identificador" => "sec0095"
              "titulo" => "Confidentiality of data"
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              "identificador" => "sec0100"
              "titulo" => "Right to privacy and informed consent"
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          "titulo" => "Conflict of interest"
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    "fechaRecibido" => "2012-06-20"
    "fechaAceptado" => "2012-10-23"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec367700"
          "palabras" => array:6 [
            0 => "Breast cancer"
            1 => "Molecular subtypes"
            2 => "Magnetic resonance imaging"
            3 => "Radiologic response"
            4 => "Neoadjuvant chemotherapy"
            5 => "Survival"
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          "identificador" => "xpalclavsec367701"
          "palabras" => array:6 [
            0 => "C&#225;ncer de mama"
            1 => "Subtipos moleculares"
            2 => "Imagen por resonancia magn&#233;tica"
            3 => "Respuesta radiol&#243;gica"
            4 => "Quimioterapia neoadyuvante"
            5 => "Supervivencia"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We included 205 patients with breast cancer treated with neoadjuvant chemotherapy&#46; We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy&#46; The pathologic response was classified on the Miller and Payne scale&#46; For each subtype &#40;HER2&#43;&#44; TN&#44; luminal A&#44; luminal B HER2&#8722;&#44; and luminal B HER2&#43;&#41;&#44; we used the <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test&#44; Student&#39;s <span class="elsevierStyleItalic">t</span>-test&#44; ANOVA&#44; and Kendall&#39;s Tau-b to evaluate the radiologic response and the pathologic response&#44; the radiologic&#8211;pathologic correlation&#44; and the disease-free survival&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The subtypes HER2&#43; &#40;62&#46;1&#37;&#41; and TN &#40;45&#46;2&#37;&#41; had higher rates of complete radiologic response&#46; The pathologic response was 65&#46;5&#37; in the HER2&#43; subtype&#44; 38&#46;1&#37; in the TN subtype&#44; 2&#46;6&#37; in the luminal A subtype&#44; 8&#46;2&#37; in the luminal B HER2&#8722; subtype&#44; and 31&#37; in the luminal B HER2&#43; subtype&#46; The rate of radiologic&#8211;pathologic correlation was significant in all subtypes&#44; higher in TN and HER2 &#40;Tau-b coefficients 0&#46;805 and 0&#46;717&#44; respectively&#41;&#46; Disease-free survival was higher in HER2&#43; &#40;91&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3 months&#41; and lower in TN &#40;69&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;3 months&#41;&#44; with significant differences between the cases with poor and good radiologic responses &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;040&#41;&#46; Survival was greater in cases with good radiologic response&#44; except in cases with luminal A subtype&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy&#44; which varies with the immunohistochemical subtype&#46;</p>"
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        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Valorar la respuesta radiol&#243;gica&#44; patol&#243;gica y su correlaci&#243;n en los subtipos moleculares del c&#225;ncer de mama y analizar su implicaci&#243;n en la supervivencia libre de enfermedad&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 205 pacientes con c&#225;ncer de mama tratadas con quimioterapia neoadyuvante&#46; Se valor&#243; la respuesta radiol&#243;gica con RM pre y posquimioterapia&#46; La respuesta patol&#243;gica se clasific&#243; seg&#250;n la escala de Miller y Payne&#46; Se valor&#243; la respuesta radiol&#243;gica y patol&#243;gica en cada subtipo &#40;HER2&#43;&#44; TN&#44; luminal A&#44; luminal B HER2&#8211; y luminal B HER2&#43;&#41;&#44; la correlaci&#243;n radiopatol&#243;gica y la supervivencia libre de enfermedad mediante las pruebas &#967;<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">t</span> de Student&#44; ANOVA y Tau-b de Kendall&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los subtipos HER2&#43; &#40;62&#44;1&#37;&#41; y TN &#40;45&#44;2&#37;&#41; mostraron mayor tasa de respuesta radiol&#243;gica completa&#46; La respuesta patol&#243;gica fue del 65&#44;5&#37; en el HER2&#43;&#44; 38&#44;1&#37; en el TN&#44; 2&#44;6&#37; en los luminales A&#44; 8&#44;2&#37; en los luminales B HER2&#8211; y 31&#37; en los luminales B HER2&#43;&#46; El &#237;ndice de correlaci&#243;n radiopatol&#243;gico fue significativo en todos los subtipos&#44; mayor en los TN y HER2 &#40;coeficientes Tau-b 0&#44;805 y 0&#44;717 respectivamente&#41;&#46; La supervivencia libre de enfermedad fue mayor para HER2&#43; &#40;91&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#44;3 meses&#41; y menor en el TN &#40;69&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;3 meses&#41;&#44; con diferencias significativas entre los casos de mala y buena respuesta radiol&#243;gica &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;040&#41;&#46; La supervivencia fue superior en los casos de buena respuesta radiol&#243;gica a excepci&#243;n del subtipo luminal A&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La RM puede ser una herramienta que aporta informaci&#243;n de la evoluci&#243;n del CM tratado con neoadyuvancia&#44; variable seg&#250;n el subtipo inmunohistoqu&#237;mico&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Cruz Ciria S&#44; Jim&#233;nez Arag&#243;n F&#44; Garc&#237;a Mur C&#44; Esteban Cuesta H&#44; Gros Ba&#241;eres B&#46; Resonancia magn&#233;tica en el c&#225;ncer de mama tratado con neoadyuvancia&#58; correlaci&#243;n radiopatol&#243;gica de la respuesta y supervivencia libre de enfermedad en funci&#243;n del subtipo molecular&#46; Radiolog&#237;a&#46; 2014&#59;56&#58;524&#8211;532&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">T1-weighted dynamic images on the axial view&#46; &#40;a&#41; Pre-chemotherapy &#40;pre-CT&#41; MRI&#58; nodular enhancement &#40;arrow&#41; of ovoid morphology and lobular contours with heterogenous enhancement occupying the mid and posterior views of lower quadrants of left breast with luminal B HER2&#8722; immunohistochemical profile&#46; &#40;b&#41; Post-CT MRI&#58; no response to neoadjuvant therapy&#46; The only difference is two &#40;2&#41; areas of central necrosis &#40;arrow&#41;&#46;</p>"
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">6 &#40;8&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab599935.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Descriptive analysis by molecular subtype&#46;</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">PR&#58; pathological response&#59; RR&#58; radiological response&#59; DFS&#58; disease-free survival&#46;</p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">TN &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">HER 2&#43; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Luminal A &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Luminal B HER2&#8722;&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Luminal B HER2&#43; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Significance&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Number of cases&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">42 &#40;19&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">29 &#40;13&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">38 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">73 &#40;34&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">29 &#40;13&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">Complete RR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;7&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17 &#40;23&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Complete PR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">16 &#40;38&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">19 &#40;65&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1 &#40;2&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">6 &#40;8&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Radiopathological correlation &#40;Kendall&#39;s Tau-b&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;805&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;717&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;709&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;606&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;554&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Relapses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;6&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;18&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;21&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;17&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;099&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DFS &#40;months&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">91&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">87&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">85&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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    "bibliografia" => array:2 [
      "titulo" => "References"
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Article information

ISSN: 21735107
Original language: English

DOI:10.1016/j.rxeng.2012.10.002

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Year/Month	Html	Pdf	Total

2024 September	5	1	6
2024 January	1	0	1
2023 December	1	0	1
2023 August	1	0	1
2023 March	2	0	2
2023 January	1	0	1
2018 May	1	0	1
2018 April	14	6	20
2018 March	22	1	23
2018 February	9	2	11
2018 January	14	1	15
2017 December	13	1	14
2017 November	14	3	17
2017 October	24	5	29
2017 September	17	6	23
2017 August	28	4	32
2017 July	31	1	32
2017 June	40	10	50
2017 May	27	7	34
2017 April	37	2	39
2017 March	47	10	57
2017 February	29	6	35
2017 January	27	3	30
2016 December	28	6	34
2016 November	28	7	35
2016 October	32	10	42
2016 September	38	8	46
2016 August	19	6	25
2016 July	41	4	45
2016 June	45	13	58
2016 May	40	14	54
2016 April	49	27	76
2016 March	45	22	67
2016 February	45	32	77
2016 January	49	25	74
2015 December	35	19	54
2015 November	31	13	44
2015 October	47	10	57
2015 September	27	11	38
2015 August	42	3	45
2015 July	33	11	44
2015 June	11	5	16
2015 May	22	7	29
2015 April	0	1	1
2015 March	2	0	2
2015 February	3	0	3
2015 January	0	1	1

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