Role of BRCA2 mutation status on overall survival among breast cancer patients from Sardinia

Germline mutations in BRCA1 or BRCA2 genes have been demonstrated to increase the risk of developing breast cancer. Conversely, the impact of BRCA mutations on prognosis and survival of breast cancer patients is still debated. In this study, we investigated the role of such mutations on breast cancer-specific survival among patients from North Sardinia. Among incident cases during the period 1997–2002, a total of 512 breast cancer patients gave their consent to undergo BRCA mutation screening by DHPLC analysis and automated DNA sequencing. The Hakulinen, Kaplan-Meier, and Cox regression methods were used for both relative survival assessment and statistical analysis. In our series, patients carrying a germline mutation in coding regions and splice boundaries of BRCA1 and BRCA2 genes were 48/512 (9%). Effect on overall survival was evaluated taking into consideration BRCA2 carriers, who represented the vast majority (44/48; 92%) of mutation-positive patients. A lower breast cancer-specific overall survival rate was observed in BRCA2 mutation carriers after the first two years from diagnosis. However, survival rates were similar in both groups after five years from diagnosis. No significant difference was found for age of onset, disease stage, and primary tumour histopathology between the two subsets. In Sardinian breast cancer population, BRCA2 was the most affected gene and the effects of BRCA2 germline mutations on patients' survival were demonstrated to vary within the first two years from diagnosis. After a longer follow-up observation, breast cancer-specific rates of death were instead similar for BRCA2 mutation carriers and non-carriers