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Revista de Senología y Patología Mamaria - Journal of Senology and Breast Disease
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Original Article
Covariate clustering: Women with breast cancer in southwestern Paraná, Brazil
Agrupamiento covariado: mujeres con cáncer de mama en el suroeste de paraná, Brasil
Neyva Maria Lopes Romeiroa,
Corresponding author
nromeiro@uel.br

Corresponding author.
, Carolina Panisb, Mara Caroline Torres dos Santosa, Daniel Rechb, Paulo Laerte Nattia, Eliandro Rodrigues Ciriloa
a Mathematics Department, Universidade Estadual de Londrina, Campus Universitário, Londrina, Brazil
b Laboratory of tumor biology, Universidade Estadual do Oeste do Paraná, UNIOESTE and Cancer Hospital, Francisco Beltrão, Brazil
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Breast cancer is the most common malignant neoplasm in women&#46;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> Age&#44; over 50&#8239;years old&#44; is the most critical risk factor&#46;<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a> Other determining factors for the development of the disease are genetic&#44; hereditary&#44; late menopause&#44; obesity&#44; sedentary lifestyle&#44; and frequent exposure to ionizing radiation&#46;<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a> Such factors are mainly responsible for the clinicopathological differences found in the literature on breast cancer&#46;<a class="elsevierStyleCrossRefs" href="#bb0025"><span class="elsevierStyleSup">5&#8211;11</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Specific studies involving the Brazilian population point to classic risk factors&#44; such as aging and menopausal status&#46;<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> Other studies show more complex associations&#44; also observed worldwide&#44; such as the development of tumors with a worse prognosis&#44; such as triple-negative&#44; in obese and overweight women&#46;<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a> Factors such as social vulnerability<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> and a history of psychological stress<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> have also been reported as possible risks associated with the presence of breast cancer in women living in southern Brazil&#46; However&#44; studies referring to regional risk factors are rare and inconclusive&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">In this context&#44; it is intended to categorize&#44; through statistical analysis&#44; possible risk factors for breast cancer&#44; targeting patients in the southwest region of Paran&#225;&#44; Brazil&#46; It is known that mathematical analysis can be a powerful tool to assess patient data&#44; providing reliable associations between variables that often cannot be understood in isolation&#46; Considering that physicians may not be familiar with statistical analysis&#44; such interdisciplinary studies become essential&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">Data from breast cancer patients can be analyzed using various mathematical tools&#46; We highlight the multivariate analysis that studies the correlation of two or more variables with different information&#46;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> The analysis of these groups can provide relevant information about part of the total sample&#46; In this way&#44; clustering performs a more specific descriptive analysis of the groups within the sample&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">It is observed that many studies perform statistical analysis considering correlations of a few variables&#46;<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bb0040"><span class="elsevierStyleSup">8&#8211;11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a> In this line of study&#44; to categorize possible risk factors identified in women diagnosed with breast cancer&#44; an exploratory data study is presented considering 11 clinicopathological variables&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Materials and methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Sample</span><p id="p0030" class="elsevierStylePara elsevierViewall">The sequential data used contain information from biopsy samples taken serially from women who had lesions suggestive of breast cancer&#44; visualized by imaging tests and physical examinations&#44; in the period from May 2015 to March 2020&#46; Data confidentiality was maintained following clinical research guidelines&#46; The Institutional Ethics Board approved the study under the number CAAE 35524814&#46;4&#46;0000&#46;0107&#44; including 155 patients with a confirmed breast cancer diagn&#243;stico through biopsy&#46; These patients from the 8<span class="elsevierStyleSup">th</span> Health Regional of the State of Paran&#225;&#44; which covers 25 municipalities&#44; divided into three regions&#44; were treated at the Oncology hospital in Francisco Beltr&#227;o&#44; Paran&#225;&#44; Brazil&#46; Medical records were consulted to obtain data&#46; All patients signed consent&#44; and each protocol followed the principles of medical research involving humans described in the Declaration of Helsinki&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Variables</span><p id="p0035" class="elsevierStylePara elsevierViewall">In this study&#44; variables with different characteristics and applications are considered&#46; The clinical and pathological variables were used to characterize patients and tumors &#40;breast cancer&#41;&#46; The spatial distribution of breast cancer cases in the three regions and municipalities of the 8<span class="elsevierStyleSup">th</span> Health Region of the State of Paran&#225; was also analyzed&#46; Numbers labeled patients&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall">Furthermore&#44; 11 clinicopathological variables are used to describe characteristics of the disease&#44; such as the presence of intratumoral emboli&#44; the presence of lymph nodes&#44; the menopausal status&#44; the molecular subtype&#44; the histological grade&#44; the TNM staging of the disease&#44; tumor size &#40;cm&#41;&#44; age at diagn&#243;stico &#40;years&#41;&#44; weight &#40;kg&#41;&#44; height &#40;m&#41; and body mass index &#40;BMI&#41; in &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46;</p><p id="p0045" class="elsevierStylePara elsevierViewall">Histopathological evaluation is essential for the diagn&#243;stico of neoplasia&#46; In this context&#44; for the histological grade variable&#44; the criteria were adopted as being well&#44; moderately&#44; and little differentiated&#46; For molecular subtype&#44; variables were determined as recommended by the St Gallen Consensus&#46;<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> The TNM staging variable was classified concerning the stages of the disease as described by the American Joint Committee on Cancer&#44; Breast Cancer Staging System&#46;<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a></p><p id="p0050" class="elsevierStylePara elsevierViewall">For a better understanding of the work&#44; the variables are classified as&#58;</p><p id="p0055" class="elsevierStylePara elsevierViewall">Binary&#58; intratumoral emboli&#44; lymph node invasion&#44; and menopausal status&#59;</p><p id="p0060" class="elsevierStylePara elsevierViewall">Categorical&#58; molecular subtype&#44; histological grade&#44; and TNM staging&#59;</p><p id="p0065" class="elsevierStylePara elsevierViewall">Quantitative&#58; tumor size&#44; age at diagn&#243;stico&#44; weight&#44; height&#44; and BMI&#46;</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Statistical methods</span><p id="p0070" class="elsevierStylePara elsevierViewall">Several methodologies analyze characteristics that differentiate the data from a sample&#44; dividing it into clusters&#46;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> In this article&#44; we used the software R&#46;<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> The packages Hmisc<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> and Agricolae<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a> were used to facilitate the interpretation of the analysis performed on the data&#46; Cluster analysis was performed by calculating the Euclidean distance between clinicopathological variables&#46;</p><p id="p0075" class="elsevierStylePara elsevierViewall">Initially&#44; to determine which data are more homogeneous with each other&#44; the Euclidean distance method is used&#46; Next&#44; Ward&#39;s hierarchical agglomerative method is used to generate the heterogeneous groups among themselves&#46; The result of the analysis&#44; presented in a dendrogram&#44; helps identify the division of groups&#44; thus generating clusters&#46;</p><p id="p0080" class="elsevierStylePara elsevierViewall">Once the clusters were obtained&#44; the calculation of Spearman&#39;s lineal correlation between the variables allowed us to understand the influence that one variable exerts over another&#44; enabling the identification of possible risk factors associated with the groups&#46;<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> The Spearman&#39;s correlation coefficient varies between &#8722;<span class="elsevierStyleHsp" style=""></span>1 and 1&#44; where&#44; to determine the significance of the correlations&#44; the <span class="elsevierStyleItalic">p</span>-value was calculated&#46;</p><p id="p0085" class="elsevierStylePara elsevierViewall">To extract characteristics that distinguish the data from different clusters and calculate the correlation&#44; the test of means was used&#46; This procedure allows us to calculate&#44; for each cluster variable&#44; those that present different significant means and those that are just sample variations&#46;</p></span></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Results</span><p id="p0090" class="elsevierStylePara elsevierViewall">Approximately 31&#37; of the patients had tumors containing intratumoral emboli&#46; It is also noted that the presence of positive lymph nodes was observed in 41&#37; of patients and that 70&#37; are classified as menopausal women at diagn&#243;stico&#46;</p><p id="p0095" class="elsevierStylePara elsevierViewall">On average&#44; the patients in this study have a higher frequency of tumors of the Luminal B molecular subtype&#44; intermediate histological grade&#44; moderately differentiated&#44; and a median TNM stage II&#44; with variations between 0 and IV&#46;</p><p id="p0100" class="elsevierStylePara elsevierViewall">The dispersion of tumor size was observed&#44; ranging from 0&#46;9&#8239;cm to 15&#8239;cm&#46; The average age of patients is 56&#46;6&#8239;years&#44; and the prevalence of the disease was higher in women aged over 45&#8239;years&#44; representing 75&#37; of cases&#46; The average weight&#44; when diagnosed&#44; was close to 72&#46;5&#8239;kg&#44; but one of the patients weighed 120&#8239;kg&#46; Furthermore&#44; only 25&#37; of patients had a BMI of less than 24&#46;8&#8239;kg&#47;m<span class="elsevierStyleSup">2</span>&#46;</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Clinicopathological correlations</span><p id="p0105" class="elsevierStylePara elsevierViewall">Checking the influence that one variable exerts on the other allows a better understanding of the data from a sample&#44; making it possible to identify possible risk factors&#46; Thus&#44; Spearman&#39;s lineal correlation is used to estimate the correlation between each pair of variables&#44; evaluating possible connections between clinicopathological variables&#46;</p><p id="p0110" class="elsevierStylePara elsevierViewall">Statistical analysis reveals the existence of significant associations between some of the variables in the sample&#46; These results can be seen through the color map in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#44; where stronger colors reveal the existence of significant associations &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;01&#41; between the variables&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0115" class="elsevierStylePara elsevierViewall">We should highlight the positive and significant correlations of intratumoral emboli with the presence of lymph node invasion and TNM staging&#46; The formation of intratumoral emboli occurs due to tumor-induced coagulation changes&#46; This event facilitates the spread of the disease&#44; explaining its correlation with lymph node invasion&#46;<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a></p><p id="p0120" class="elsevierStylePara elsevierViewall">TNM staging variable presents a positive and significant correlation with the lymph node invasion variable&#46; This correlation was also expected&#44; as the TNM staging calculation uses lymph node invasion as one of its parameters&#46; These results show that the mathematical model follows the clinical classification used to establish the TNM staging&#46;</p><p id="p0125" class="elsevierStylePara elsevierViewall">It is noted that the correlations involving the variables presence of intratumoral emboli&#44; lymph node invasion&#44; and TNM staging did not show significant connections with the variables age and BMI&#44; so that the correlations presented describe risk factors independent of age and the patients&#39; body weight at diagn&#243;stico&#46; However&#44; it is known that both age and obesity are considered determinant risk factors&#46; <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a> shows a positive and robust correlation between menopause and the patient&#39;s age&#46; It is an expected association&#44; as women experience hormonal failure with aging&#46; On the other hand&#44; the data do not show a significant correlation between menopause and being overweight&#46;</p><p id="p0130" class="elsevierStylePara elsevierViewall">Due to the heterogeneity of the behavior patterns of the clinical parameters evaluated in breast cancer&#44; it is necessary to analyze the sample data in smaller groups&#46; Thus&#44; probably more specific correlations can be evidenced from the data&#46;</p><p id="p0135" class="elsevierStylePara elsevierViewall">Considering the data from the complete sample&#44; Ward&#39;s method resulted in the formation of hierarchical groups by similarities&#44; suggesting a marked reduction in similarity when 2 or 3 clusters are obtained&#44; as shown in <a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>&#46; The dendrogram graphically indicates the evolutionary history of the distance matrix&#59; that is&#44; the observations of each group are similar to each other&#44; and each group is heterogeneous compared to the other&#44; so three groups were the ideal choice&#46; In addition to the dendrogram&#44; the fusion test was performed&#44; indicating that the first most significant distance between the groups is found in the third group&#46; Thus&#44; it was decided to keep 3 clusters&#44; denoted by C<span class="elsevierStyleInf">1</span>&#44; C<span class="elsevierStyleInf">2</span>&#44; and C<span class="elsevierStyleInf">3</span>&#44; respectively&#44; even because&#44; clinically&#44; there was a better representation of information about the patients&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0140" class="elsevierStylePara elsevierViewall">From the descriptive means and test of means&#44; <a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#44; it appears that clusters C<span class="elsevierStyleInf">1</span>&#44; C<span class="elsevierStyleInf">2</span>&#44; and C<span class="elsevierStyleInf">3</span> do not show significant differences in the variables intratumoral emboli&#44; presence of lymph node invasion&#44; molecular subtype&#44; grade&#44; TNM staging&#44; tumor size&#44; and height&#46; On the other hand&#44; all clusters show significant differences in the menopausal status&#44; age&#44; weight&#44; and BMI variables&#44; in bold in <a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#46; Thus&#44; in our mathematical modeling&#44; the variable menopause&#44; age&#44; and BMI at diagn&#243;stico were selected based on their contribution to characterizing the influence of each variable in breast cancer prognosis&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Discussion</span><p id="p0145" class="elsevierStylePara elsevierViewall">In this study&#44; we showed that cluster analysis is an interesting approach to categorizing breast cancer patients according to combined clinicopathological features&#46; This analysis resulted in 3 utterly distinct clusters&#46; C<span class="elsevierStyleInf">1</span> was formed by 99&#37; of menopausal women&#44; older&#44; with a mean age of 67&#8239;years&#44; and overweight&#44; with a mean BMI of 27&#46;14&#8239;kg&#47;m<span class="elsevierStyleSup">2</span>&#46; C<span class="elsevierStyleInf">2</span> included younger women with a mean of 42&#46;57&#8239;years&#59; most were not in menopause&#44; had lymph node invasion&#44; and had average weight&#46; C<span class="elsevierStyleInf">3</span> was composed of women of middle ages&#44; obese&#44; in menopause&#44; and with lymph node invasion&#46;</p><p id="p0150" class="elsevierStylePara elsevierViewall">Information regarding the categorical and quantitative variables in each cluster is shown in <a class="elsevierStyleCrossRef" href="#f0010">Fig&#46; 2</a>&#46; Note that <a class="elsevierStyleCrossRef" href="#f0010">Fig&#46; 2</a>&#40;a&#41; shows the prevalence of tumors of the Luminal A and B subtypes in C<span class="elsevierStyleInf">1</span> and C<span class="elsevierStyleInf">3</span> and Luminal B in C<span class="elsevierStyleInf">2</span>&#46; It means that considering the molecular subtype of breast cancer&#44; C<span class="elsevierStyleInf">2</span> has patients with the worst clinical prognosis compared to the others since Luminal B tumors are very aggressive&#46;<a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a></p><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0155" class="elsevierStylePara elsevierViewall">It was observed that with the division of clusters&#44; it was possible to characterize the heterogeneity of behavior between the clinicopathological variables&#46; Quantifying the intensity of the statistical dependence of the set of variables in each cluster will allow us to understand the influence that one variable exerts over another&#44; making it possible to identify possible risk factors associated with the groups&#46;</p><p id="p0160" class="elsevierStylePara elsevierViewall">Thus&#44; from the analysis of each cluster&#44; where stronger colors reveal the existence of significant associations &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;01&#41; between the variables&#44; as shown in <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>&#44; the data confirm some common characteristics&#44; highlighting the strong correlation between the variables weight and BMI in all clusters&#44; and the correlation between menopausal status and age at diagn&#243;stico&#44; in C<span class="elsevierStyleInf">3</span>&#46; Similarly&#44; correlations between intratumoral emboli&#44; the presence of lymph node invasion&#44; and TNM staging are present in almost all clusters&#46; It is worth mentioning that&#44; despite these characteristics having already been observed in the data of the complete sample&#44; <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#44; it is now possible to analyze these correlations in the context of the particularities of each cluster&#46; Next&#44; the analysis of each cluster was carried out&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia><p id="p0165" class="elsevierStylePara elsevierViewall">In C<span class="elsevierStyleInf">1</span>&#44; menopausal&#44; older&#44; and overweight patients&#44; significant correlations between the variables intratumoral emboli&#44; lymph node invasion&#44; and TNM staging are observed&#46; This statement is justified by the analysis of the correlations obtained in <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>&#44; that is&#44; the correlation of&#58;</p><p id="p0170" class="elsevierStylePara elsevierViewall">&#40;a&#41; intratumoral emboli with lymph node invasion and TNM staging&#44;</p><p id="p0175" class="elsevierStylePara elsevierViewall">&#40;b&#41; TNM staging with lymph node invasion&#44; tumor grade&#44; and size&#46;</p><p id="p0180" class="elsevierStylePara elsevierViewall">It is known that&#44; clinically&#44; the formation of intratumoral emboli occurs due to coagulation alterations induced by tumors&#44; facilitating the process of spreading the disease&#46; Furthermore&#44; the larger the tumor size&#44; the more advanced the TNM stage of the disease is&#46;</p><p id="p0185" class="elsevierStylePara elsevierViewall">In C<span class="elsevierStyleInf">2</span>&#44; composed of patients aged between 31 and 52&#8239;years&#44; most of them not menopausal and with an average BMI of 24&#46;11&#8239;kg&#47;m<span class="elsevierStyleSup">2</span>&#46; There are significant correlations between intratumoral emboli and lymph node invasion&#44; without association with the obesity variable&#46; This statement is justified by the analysis of the correlations obtained in <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>&#44; that is&#44; the correlation of&#58;<ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="li0005"><span class="elsevierStyleLabel">&#40;a&#41;</span><p id="p0190" class="elsevierStylePara elsevierViewall">intratumoral emboli with lymph node invasion&#44;</p></li><li class="elsevierStyleListItem" id="li0010"><span class="elsevierStyleLabel">&#40;b&#41;</span><p id="p0195" class="elsevierStylePara elsevierViewall">TNM staging with lymph node invasion and tumor size&#46;</p></li></ul></p><p id="p0200" class="elsevierStylePara elsevierViewall">Clinically&#44; these correlations act in favor of the same biological event&#44; which in this case would be favoring tumor spread&#46; In addition&#44; this association has a significant clinical meaning since this cluster is characterized by the incidence of the disease in young women&#44; which gives them a risk of highly aggressive tumors&#46;<a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a> Thus&#44; these women are not in menopause at diagn&#243;stico is another factor of worse prognosis because estrogen acts as fuel for breast cancer&#46;<a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a></p><p id="p0205" class="elsevierStylePara elsevierViewall">In C<span class="elsevierStyleInf">3</span>&#44; composed of patients considered young&#44; obese&#44; and with a prevalence of TNM staging in stages&#44; II and III&#44; presents a strong correlation between the menopausal status variables and age at diagn&#243;stico&#44; in addition to other correlations previously observed in the preceding clusters&#46; This statement is justified by the analysis of the correlations obtained in <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>&#44; that is&#44; the correlation of&#58;<ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="li0015"><span class="elsevierStyleLabel">&#40;a&#41;</span><p id="p0210" class="elsevierStylePara elsevierViewall">intratumoral emboli with lymph node invasion and TNM staging&#44;</p></li><li class="elsevierStyleListItem" id="li0020"><span class="elsevierStyleLabel">&#40;b&#41;</span><p id="p0215" class="elsevierStylePara elsevierViewall">TNM staging with intratumoral emboli&#44; lymph node invasion&#44; and molecular subtype&#44;</p></li><li class="elsevierStyleListItem" id="li0025"><span class="elsevierStyleLabel">&#40;c&#41;</span><p id="p0220" class="elsevierStylePara elsevierViewall">menopausal status with age at diagn&#243;stico&#46;</p></li></ul></p><p id="p0225" class="elsevierStylePara elsevierViewall">Clinically&#44; the strong correlation between the variables menopausal status and age at diagn&#243;stico configures a worse disease prognosis for non-menopausal women&#46; There is no correlation between obesity and variables associated with breast cancer in these data&#46; On the other hand&#44; in the literature&#44; it is observed that obesity is a risk factor for breast cancer and is associated with the occurrence of highly aggressive tumors&#46;<a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0160"><span class="elsevierStyleSup">32</span></a></p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">Spatial distribution of clinicopathological variables</span><p id="p0230" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#t0020">Table 4</a> presents the descriptive means of the variables considered in each cluster for the three regions of the 8<span class="elsevierStyleSup">th</span> Health Regional of the State of Paran&#225;&#44; that are&#58; Fronteira&#44; Vale do Igua&#231;u&#44; and Vale do Marrecas&#46; Note that the means of the variables in each region that stand out the most are cluster C<span class="elsevierStyleInf">2</span>&#44; in bold in <a class="elsevierStyleCrossRef" href="#t0020">Table 4</a>&#46; Although the Vale do Igua&#231;u region contains the smallest number of patients&#44; those in C<span class="elsevierStyleInf">2</span> of this region showed that the youngest patients are in a very advanced stage of the disease&#44; TNM III&#44; with the worst prognosis&#46;</p><elsevierMultimedia ident="t0020"></elsevierMultimedia><p id="p0235" class="elsevierStylePara elsevierViewall">Regarding the high frequency of patients who developed the disease in the Vale do Marrecas region&#44; this area is reported as the highest pesticide trade in in Paran&#225; state&#44; and it includes all municipalities in the 8<span class="elsevierStyleSup">th</span> Health Regional&#46;<a class="elsevierStyleCrossRef" href="#bb0165"><span class="elsevierStyleSup">33</span></a> Therefore&#44; knowledge about the spatial distribution of pesticide use can be used as a variable for the prognosis of breast cancer and give a possible interpretation of the data presented in <a class="elsevierStyleCrossRef" href="#t0020">Table 4</a>&#46; Thus&#44; new analyzes are suggested to assess the impacts of extrinsic factors on breast cancer patients&#44; especially environmental factors&#44; health habits&#44; and diet&#46;</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Conclusion</span><p id="p0240" class="elsevierStylePara elsevierViewall">The cluster analysis allowed us to identify essential factors in breast cancer and their relationship with characteristics of worse prognosis&#44; such as BMI&#44; TNM staging&#44; the presence of intratumoral emboli&#44; and lymph nodal invasion&#46; Due to the heterogeneity of the clinical parameters evaluated&#44; the sample data was analyzed in smaller groups&#44; which resulted in three hierarchical groups categorized by similarities based on cluster analysis&#46; All groups showed significant differences in menopausal status&#44; age and BMI&#59; therefore&#44; these variables were selected&#46;</p><p id="p0245" class="elsevierStylePara elsevierViewall">Through the statistical analysis&#44; it was possible to determine the heterogeneity of the data&#44; so the patients were separated into three clusters&#46; This analysis identified that the group composed of older&#44; postmenopausal and obese patients with intratumoral emboli&#44; and lymph node invasion&#44; configured characteristics of worse prognosis&#46; As young&#44; non-menopausal&#44; and eutrophic patients who presented intratumoral emboli and lymph node invasion had characteristics associated with the development of tumors with poor clinical prognosis&#44; regardless of obesity&#46; Another group was formed by patients considered young&#44; in menopause&#44; and obese who presented a prevalence of TNM staging in stages II and III&#44; reflecting the failures in the late search for health services for screening the disease at earlier stages&#46; When analyzing the obtained clusters&#44; each one of them had singular characteristics&#46; Thus&#44; with the division of the groups&#44; it was possible to characterize the heterogeneity of characteristics of the clinicopathological variables&#44; especially when considering that BMI is not a classical risk factor used to predict patients&#39; prognosis in breast cancer&#46; Quantifying the intensity of the statistical dependence of the set of variables in each cluster allowed us to understand the influence that one variable exerts over another&#44; enabling the identification of possible risk factors associated with the groups&#46;</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0115">Funding</span><p id="p0250" class="elsevierStylePara elsevierViewall">The authors declare that they have not received funding for this study&#46;</p></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0120">Ethical disclosures</span><p id="p0255" class="elsevierStylePara elsevierViewall">All patients signed consent forms&#46; The study was approved by the Institutional Ethical Committee&#46; The authors have no ethical issues to declare&#46;</p></span></span>"
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        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Introduction</span><p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">Due to the high incidence and aggressiveness of breast cancer&#44; understanding specific factors associated with the profile of the disease is necessary&#46; Thus&#44; the study aimed to analyze data from 155 patients with breast cancer&#44; grouping them according to their clinicopathological characteristics&#44; attended at a reference hospital for Oncology&#44; in 2015&#8211;2020&#44; in the southwest region of Paran&#225;&#44; Brazil&#46;</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Material and Methods</span><p id="sp0060" class="elsevierStyleSimplePara elsevierViewall">Using multivariate statistical analysis&#44; sample data were divided into three clusters&#46; The heterogeneity between clusters was obtained by Ward&#39;s method&#46; The clinicopathological variables obtained from the patients&#39; medical records were&#58; the presence of intratumoral emboli and lymph nodes&#44; menopausal status&#44; molecular subtype&#44; histological grade&#44; TNM staging of the disease&#44; tumor size&#44; age at diagn&#243;stico&#44; weight&#44; height&#44; and body mass index&#46;</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Results</span><p id="sp0065" class="elsevierStyleSimplePara elsevierViewall">It is observed that 70&#37; of the patients were in menopause at diagn&#243;stico&#44; 31&#46;5&#37; had tumors containing emboli&#44; and 41&#37; had positive lymph nodes&#46; The prevalence of Luminal B subtype&#44; intermediate histological grade&#44; and TNM staging II was verified&#46; The prevalence of the disease was higher in women aged over 50&#8239;years&#44; representing 66&#37; of cases&#46; The BMI of the patients ranged from 17&#46;63&#8239;kg&#47;m<span class="elsevierStyleSup">2</span> to 51&#46;26&#8239;kg&#47;m<span class="elsevierStyleSup">2</span>&#44; with 73&#46;55&#37; above 25&#8239;kg&#47;m<span class="elsevierStyleSup">2</span>&#46; Using the spatial distribution of patients&#44; cluster analysis identified the regions with the worst averages of clinicopathological variables and the highest number of cancer cases&#46;</p></span> <span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Conclusion</span><p id="sp0070" class="elsevierStyleSimplePara elsevierViewall">Through the statistical analysis&#44; it was possible to determine the heterogeneity of the data&#44; so the patients were separated into three clusters&#46; When analyzing the obtained clusters&#44; each one of them had specific characteristics&#46;</p></span>"
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        "resumen" => "<span id="as0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Introducci&#243;n</span><p id="sp0075" class="elsevierStyleSimplePara elsevierViewall">Debido a la alta incidencia y agresividad del c&#225;ncer de mama&#44; es necesario el conocimiento de factores espec&#237;ficos asociados al perfil de la enfermedad&#46; As&#237;&#44; el objetivo del estudio fue analizar datos de 155 pacientes con c&#225;ncer de mama&#44; agrup&#225;ndolas seg&#250;n sus caracter&#237;sticas cl&#237;nico-patol&#243;gicas&#44; atendidas en un hospital de referencia en Oncolog&#237;a&#44; en el per&#237;odo 2015&#8211;2020&#44; en la regi&#243;n suroeste de Paran&#225;&#44; Brasil&#46;</p></span> <span id="as0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Material y m&#233;todos</span><p id="sp0080" class="elsevierStyleSimplePara elsevierViewall">A partir de la utilizaci&#243;n de un an&#225;lisis estad&#237;stico multivariado&#44; los datos de la muestra se dividieron en tres grupos&#46; La heterogeneidad entre cl&#250;steres se obtuvo mediante el m&#233;todo de Ward&#46; Las variables cl&#237;nico-patol&#243;gicas obtenidas de la historia cl&#237;nica de las pacientes fueron&#58; presencia de &#233;mbolos y ganglios linf&#225;ticos intratumorales&#44; estado menop&#225;usico&#44; subtipo molecular&#44; grado histol&#243;gico&#44; estadificaci&#243;n TNM de la enfermedad&#44; tama&#241;o tumoral&#44; edad al momento del diagn&#243;stico&#44; peso&#44; talla&#44; e &#237;ndice de masa corporal&#46;</p></span> <span id="as0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Resultados</span><p id="sp0085" class="elsevierStyleSimplePara elsevierViewall">Se observa que el 70&#37; de las pacientes se encontraba en menopausia al momento del diagn&#243;stico&#44; el 31&#44;5&#37; ten&#237;a tumores con &#233;mbolos y el 41&#37; ten&#237;a ganglios positivos&#46; Se verific&#243; la prevalencia de subtipo luminal B&#44; grado histol&#243;gico intermedio y estadificaci&#243;n TNM II&#46; La prevalencia de la enfermedad fue mayor en mujeres mayores de 50 a&#241;os&#44; lo que representa el 66&#37; de los casos&#46; El IMC de los pacientes oscil&#243; entre 17&#44;63&#8239;kg&#47;m<span class="elsevierStyleSup">2</span> y 51&#44;26&#8239;kg&#47;m<span class="elsevierStyleSup">2</span>&#44; con un 73&#44;55&#37; encima de 25&#8239;kg&#47;m<span class="elsevierStyleSup">2</span>&#46; El an&#225;lisis de cl&#250;ster&#44; utilizando la distribuci&#243;n espacial de pacientes&#44; identific&#243; las regiones con los peores promedios de variables cl&#237;nico-patol&#243;gicas y el mayor n&#250;mero de casos de c&#225;ncer&#46;</p></span> <span id="as0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Conclusi&#243;n</span><p id="sp0090" class="elsevierStyleSimplePara elsevierViewall">A trav&#233;s del an&#225;lisis estad&#237;stico fue posible determinar la heterogeneidad de los datos&#44; por lo que las pacientes fueron separadas en tres grupos&#46; Al analizar los cl&#250;steres obtenidos&#44; pudo verificarse que cada uno de ellos presentaba caracter&#237;sticas espec&#237;ficas&#46;</p></span>"
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          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Spearman&#39;s correlations and <span class="elsevierStyleItalic">p</span>-value &#40;in parentheses&#41; for the 155 patients diagnosed with breast cancer&#46;</p>"
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                  \t\t\t\t">1&#46;93&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;95&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">1&#46;91&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">1&#46;90&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TNM staging&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;06&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;96&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;09&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Quantitative variables</span></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">&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tumor size &#40;cm&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;18&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;11&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;51&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;years&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#46;64&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">67&#46;06</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">a</span></span>&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">42&#46;57</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">48&#46;56</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">b</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Weight &#40;kg&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;54&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">68&#46;66</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">b</span></span>&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">62&#46;59</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">88&#46;54</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">a</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Height &#40;m&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;60&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;59&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;61&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;25&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">27&#46;14</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">b</span></span>&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">24&#46;11</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">33&#46;94</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">a</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Spearman&#39;s correlations and <span class="elsevierStyleItalic">p</span>-value &#40;in parentheses&#41; of variables for clusters C<span class="elsevierStyleInf">1</span>&#44; C<span class="elsevierStyleInf">2</span> and C<span class="elsevierStyleInf">3</span>&#46;</p>"
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          "leyenda" => "<p id="sp0050" class="elsevierStyleSimplePara elsevierViewall">The means of the variables that stood out among the clusters in the respective regions are shown in bold&#46; Higher mean frequencies of patients who presented the presence of intratumoral emboli and lymph node&#59; higher means for categorical variables Molecular subtype&#44; grad&#44; and TNM staging&#44; configuring worse prognosis&#46; Largest tumor size averages&#46; Lower and higher mean age and BMI&#44; respectively&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" 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" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fronteira</th><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vale do Igua&#231;u</th><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vale do Marrecas</th></tr><tr title="table-row"><th 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" scope="col" 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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">C<span class="elsevierStyleInf">1</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">C<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">C<span class="elsevierStyleInf">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">C<span class="elsevierStyleInf">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">C<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">C<span class="elsevierStyleInf">3</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">C<span class="elsevierStyleInf">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">C<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">C<span class="elsevierStyleInf">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Number of patients&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="10" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Binary variables</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intratumoral emboli&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;30&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
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                  \t\t\t\t">Lymph node invasion&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Menopausal status&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Molecular subtype&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">TNM staging&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Quantitative variables</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">Tumor size &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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ISSN: 02141582
Original language: English
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos