Expressão de marcadores biológicos em câncer de mama antes e após a quimioterapia neoadjuvante. I- Correlações com desfechos clínicos e entre marcadores
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Data
2014-08-05
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Universidade Federal de Goiás
Resumo
With the exception of skin cancer, breast cancer remains the most common malignant neoplasm affecting women both in Brazil and worldwide, inflicting severe economic, social and emotional consequences on patients and their families. Despite advances made in diagnostic and therapeutic techniques over recent decades, mortality rates from breast cancer remain expressive. To be able to treat tumors appropriately, not only profound knowledge of the cell mechanisms involved in their genesis, but also knowledge of the mechanisms involved in the success or failure of treatment is crucial. Various methods have been developed for this purpose, including the evaluation of biological tumor markers and the genetic studies. The objective of the present study was to evaluate some biological markers involved in the differentiation and evolution of breast cancer, using immunohistochemistry on tissue arrays. A retrospective study was conducted between 2006 and 2012 in which clinical data were obtained from patient charts, and tissue samples conserved in paraffin blocks were prospectively analyzed and correlated with each other and with the patient’s response to neoadjuvant chemotherapy. The results were presented in two papers. In the first article, biomarker expression was evaluated in biopsy specimens obtained at diagnosis and then following treatment with adjuvant chemotherapy, with correlations being drawn between the differences found. Statistically significant differences were found in Ki-67, IGF-1, topoisomerase II-alpha and CK5/6 marker expression, indicating the effect of chemotherapy on the proliferation index of the malignant breast tumors. On the other hand, no statistically significant differences were found in HER2, estrogen and progesterone receptors, PTEN or EGFR. In the second paper, correlations were sought between biological marker expression and the patient’s outcome response to previous chemotherapy, with results showing significant correlations between the HER2 and topoisomerase II-alpha markers and pathologic complete response despite the fact that the sample was small. No other statistically significant correlations were found with any of the other markers evaluated. When molecular subtypes were analyzed, the study showed a greater frequency of pathologic complete response for the HER2 subtype and this difference was statistically significant. Another important result was the correlation between the tendency towards a reduction in mean Ki-67 values and a clinical benefit from the treatment implemented a finding that led to the preparation of a third paper, which consisted of an integrative review of the Ki-67 marker. This review concluded that further studies need to be conducted on the Ki-67 marker and that its expression should be analyzed dynamically to establish whether a correlation exists between this marker and patients’ prognosis and whether Ki-67 is a predictor of treatment response.
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Biomarcadores , Câncer de mama , Ki67 , Predição , Prognóstico , Biomarkers , Breast cancer , Ki67 , Prediction , Prognostic
Citação
GABRIEL, Augusto Ribeiro. Expressão de marcadores biológicos em câncer de mama antes e após a quimioterapia neoadjuvante. I- Correlações com desfechos clínicos e entre marcadores. 2014. 140 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2014.