Several studies have shown that among ovarian cancer patients, BRCA1 and especially BRCA2 carriers respond better than non-carriers to platinum-based chemotherapy and have prolonged survival 20, 21, 22. Ovarian cancers are frequently diagnosed at advanced stages and receive platinum-based chemotherapy 19. The majority of ovarian cancers that develop in BRCA carriers (either BRCA1 or BRCA2) are high-grade serous ovarian carcinomas (HGSOC). BRCA carriers with TNBC have been shown to be more sensitive to DNA-damaging agents 9, 10, 11, 12, 13, 14, 15 but this did not translate into a survival benefit 6, 9, 12, 16, 17.īRCA germline mutations account for approximately 10–15% of ovarian cancers 18. Currently, there are conflicting data regarding the predictive and prognostic values of BRCA mutations on the survival of non-metastatic breast cancer patients 6, 7, 8. Not all BRCA carriers who develop breast cancer receive adjuvant chemotherapy, depending on several factors, including tumor stage, grade and molecular subtype. BRCA1 mutation carriers mainly develop triple negative breast cancers (TNBC), whereas BRCA2 carriers are more likely to develop estrogen receptor (ER) and/or progesterone receptor (PR) positive tumors 5. In breast cancer patients, the tumor phenotype differs according to the BRCA1 or BRCA2 germline mutation status. As a consequence, tumors harboring deleterious mutations of BRCA1/BRCA2 genes are highly sensitive to DNA-damaging agents, such as interstrand crosslinking agents (platinum or alkylating agents), topo-isomerase II inhibitors (anthracyclines) or PARP inhibitors 2, 3, 4. Cells with non-functional BRCA1/BRCA2 proteins are severely impaired in their ability to repair DNA double strand breaks (DSBs) through homologous recombination 2.
These tumor suppressor genes encode large, ubiquitous and multifunctional proteins that play a central role in DNA repair, cell-cycle control and chromosomal stability 2. These results suggest that BRCA1/BRCA2 germline mutations are associated with prolonged survival only if women were diagnosed with TNBC.īRCA1/BRCA2 germline mutations account for approximately 5% of all breast cancers 1. In the non-TNBC group, the BRCA1 or BRCA2 mutations did not have any impact on survival.
In the entire cohort, there was a prolonged disease-free survival (DFS) for BRCA carriers (hazard ratio (HR) = 0.63 95% confidence interval (CI), 0.44–0.90 for BRCA1 HR = 0.72 95%CI, 0.47–1.1 for BRCA2 p = 0.020) and a trend toward prolonged disease-specific survival (DSS HR = 0.65 95%CI, 0.40–1.1 for BRCA1 HR = 0.78 95%CI, 0.44–1.38 for BRCA2 p = 0.19) though not statistically significant. Overall, 171 women carried a BRCA1 mutation, 95 carried a BRCA2 mutation, and 659 were non-carriers.
We collected clinical, pathological and genetic data of a cohort 925 BC patients preselected for genetic screening and treated with neoadjuvant or adjuvant chemotherapy, of whom 266 were BRCA carriers.
There are conflicting data regarding the prognostic value of BRCA germline mutations in breast cancer (BC) patients. BRCA1/BRCA2 genes play a central role in DNA repair and their mutations increase sensitivity to DNA-damaging agents.
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