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

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.,Alterations (deletion/methylation/expression) of the genes were analyzed in 118 pretherapeutic and 41 NACT-treated BC samples.,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.,Alterations of homologous recombination repair pathway genes are needed for the development of BC.