Frequent alterations of homologous recombination repair pathway in primary and chemotolerant breast carcinomas: clinical importance

Abstract

Aim: To understand the importance of homologous recombination repair pathway in development of breast carcinoma (BC), alterations of some key regulatory genes like BRCA1, BRCA2, FANCC and FANCD2 were analyzed in pretherapeutic/neoadjuvant chemotherapy (NACT)-treated BC samples. Materials & methods: Alterations (deletion/methylation/expression) of the genes were analyzed in 118 pretherapeutic and 41 NACT-treated BC samples. Results: High deletion/methylation (29–68%) and 64–78% overall alterations of the genes were found in the samples. Concordance was evident between alteration and protein expression of the genes. Estrogen/progesterone receptor-negative tumors showed significantly high alterations even in NACT-treated samples having low CD44 and proliferating cell nuclear antigen expression. Pretherapeutic patients with alterations showed poor prognosis. Conclusion: Alterations of homologous recombination repair pathway genes are needed for the development of BC.