Valor preditivo de características clinico-patológicas e da expressão de genes de reparo do DNA na resposta à quimioterapia neoadjuvante em pacientes com câncer de mama

Abstract

Genome-wide analysis using microarrays has revolutionized the field of breast cancer (BC) research. A substantial body of evidence supports the clinical utilityof the 21-gene assay (Oncotype DX) and 70-gene assay (MammaPrint) to predict BC recurrence and the magnitude of chemotherapy benefit. However, there is currently no genetic tool able to predict chemosensitivity and chemoresistance to neoadjuvant chemotherapy (NACT) during BC treatment. In this study, we explored the predictive value of DNA repair gene expression in the neoadjuvant setting. We selected 98 patients with BC treated with NACT. We assessed DNA repair expression in 98 formalin-fixed, paraffin-embedded core biopsy fragments used at diagnosis and in 32 formalin-fixed, paraffin-embedded post-NACT residual tumors using quantitative reverse transcription-polymerase chain reaction. The following genes were selected: BRCA1, PALB2, RAD51C, BRCA2, ATM, FANCA, MSH2, XPA, ERCC1, PARP1, and SNM1. Of 98 patients, 33 (33.7%) achieved pathologic complete response (pCR). The DNA expression of 2 genes assessed in pre-NACT biopsies (PALB2 and ERCC1) was lower in pCR than in non-pCR patients (p=0.005 and p=0.009, respectively). There was no correlation between molecular subtype and expression of DNA repair genes. The genes BRCA2 (p=0.009), ATM (p=0.004), FANCA (p=0.001), and PARP1 (p=0.011) showed a lower expression in post-NACT residual tumor samples (n=32) than in pre-NACT biopsy samples (n=98). As conclusions, the expression of 2 genes (PALB2 and ERCC1) was lower in pCR patients and the expression of 4 genes (BRCA2, ATM, FANCA and PARP1) was lower in post-NACT residual tumor samples than in pre-NACT biopsy samples. The use of recently developed multiparameter gene-expression assays, based on the expression of genes involved in different DNA repair pathways, should be further explored in future studies, as they may facilitate the selection of patients most likely to benefit from NACT. In addition, these alterations in DNA repair could be considered suitable targets for cancer therapy. [resumo fornecido pelo autor]