1449 POSTER Molecular Breast Cancer Subtypes: Relationship With Angiogenesis Genes Polymorphism, Efficacy of Neoadjuvant Chemotherapy and Survival

Abstract

Background: Breast cancer heterogeneity suggests that specific molecular subtypes will have distinct biological characteristics and clinical behavior. The purpose of this study was to analyze the polymorphisms of angiogenesis genes and their impact on the response to treatment and outcome of breast cancer patients according to molecular cancer subtypes. Material and Methods: Our subjects comprised 272 breast cancer patients who received 2-4 cycles of neoadjuvant chemotherapy in the Tomsk Cancer Research Institute. The patients were classified into two subtypes: triple negative (TN) and non-TN. The VEGF-2578C/A (rs699947), FGFR2A/G (rs1219648) and TGFB1-509C>T (rs1800469) TGFB1-29T>C (rs1982073) genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism method. Results: A marginal trend towards significant association of TGFB1- 29(CT/TT) genotypes with positive lymph nodes status was found among non-TN patients compared to TN cases (P = 0.057). In addition, we observed that this non-TN group with TGFB1-29 (CT/TT) genotypes tended to have shorter overall survival after neoadjuvant chemotherapy than TN patients (P = 0.08). A similar pattern was found between non-TN and TN patients carrying VEGF-2578 (CC) genotype (P = 0.08). However, the survival curves of wildtype VEGF genotype patients were very similar between the non-TN and TN groups (P = 0.18). Overall survival of women with the TGFB1-509 (CT/TT) genotypes was significantly worse than for TGFB1-509 (CC) carriers independent of patients molecular subtype (P = 0.009). Only TN women carrying FGFR2 (AA) genotype showed an association with better response to neoadjuvant chemotherapy in comparison non-TN (P = 0.02). In the logistic regression analysis, the FGFR2A/G genotype and molecular subtypes were the independent factors that predicted the probability of pathological regression (P = 0.013). Conclusion: Our study indicates that the analysis of angiogenesis-related gene polymorphisms may help to identify patient subgroups at high risk for the progression of breast cancer. FGFR2A/G may be considered as a prognostic factor for efficacy to neoadjuvant chemotherapy in TN patients.