Role of BRCA2 mutation status on overall survival among breast cancer patients from 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.The breast cancer is a complex disease with high biological heterogeneity and wide spectrum of responsiveness to different treatments. The well-established prognostic factors currently used into the management of patients with breast carcinoma include the disease stage (which takes into account tumour size, axillary lymph node involvement, and distant tumour dissemination) as well as the histological type, the degree of differentiation (tumour grade), the proliferation index, and the receptor status [estrogen receptor (ER), progesterone receptor (PR), and, recently, HER2] of the primary tumours [1]. Among them, the expression levels of hormone receptors seem to better predict the