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

Background: Germline mutations inBRCA1orBRCA2genes 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.Methods: Among incident cases during the period 1997–2002, a total of 512 breast cancer
patients gave their consent to undergoBRCAmutation 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.Results: In our series, patients carrying a germline mutation in coding regions and splice
boundaries ofBRCA1andBRCA2genes 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 inBRCA2mutation 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.Conclusion: In Sardinian breast cancer population,BRCA2was the most affected gene and the
effects ofBRCA2germline 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 forBRCA2mutation carriers and non-carriers.