BRCA1/2 and clinical outcome in a monoinstitutional cohort of women with hereditary breast cancer

The clinical outcome of BRCA mutation carriers and non-carriers still remains a topic of discussion. In order to interpret controversial data, in the present study, we analyzed a large consecutive monoinstitutional series of breast cancer patients and relatives with familial features carrying or not carrying BRCA mutations. The intense research in recent years regarding the clinical genetics of patients with breast or ovarian cancer and their relatives has allowed the organization of a unique database comprising anamnestic, clinical, pathological and molecular data. Families with two or more cases of breast cancer under the age of 50 years, or with three cases at any age, were identified. From June, 2003 to June, 2010, a total of 202 patients (136 probands + 66 relatives) from 45 families were included in the analysis. A total of 136 (49 carrier and 87 non-carrier) cases had a cancer diagnosis at the time of their genetic testing. Twenty and 24 events were observed in the carrier and control group, respectively. The 10-year disease-free suvival rate was 57% for patients in the control group compared with 50% for patients carrying a BRCA mutation (P=0.15 by log-rank test). Finally, 66 (32 genetic and 34 control) cases were unaffected at the time of molecular analysis, and 6 new cases of cancer were observed in the carriers, while no new cases were detected in the control cohort. Thus, at age 50, 40% of carriers had a high risk of disease (P=0.0069 by log-rank test). Our data support the hypothesis that the presence of BRCA mutations does not alter the clinical outcome for hereditary breast cancer patients. Conversely, BRCA mutations are proven to be crucial for prediction of risk in healthy relatives from carrier families.