Results of a population-based screening for hereditary breast cancer in a region of North-Central Italy: contribution of BRCA1/2 germ-line mutations

BRCA1/2 mutation status is of paramount importance to identify families at risk of Hereditary Breast and Ovarian Cancer (HBOC). Most HBOC and BRCA1/2 mutation studies have focused on highly selected sub-populations, and few data are available for large population cohorts. For this reason, as part of a regional cancer prevention strategy in North-Central Italy, we set up a population-based screening programme to identify all resident HBOC families, and to determine their BRCA1/2 mutation status. To date, 44 different BRCA1/2 variants have been identified in 55 HBOC families. Of the seven newly reported mutations, only BRCA1 Q284X is clearly deleterious. The analysis of clinical disease characteristics in relation to age of disease onset and family history showed a difference between BRCA1/2 wild type and mutation carrier families. Interestingly, BRCA1/2 mutations were significantly more common in women who developed breast cancer ≤40 years of age than in BRCA1/2 wild type women (50% vs. 29%, respectively, P = 0.005). The family history selection criteria most likely to indicate the presence of deleterious BRCA1/2 mutations are breast cancer ≤35 years (P = 0.012), two first-degree relatives with breast cancer ≤50 years (P = 0.022), and male breast cancer (P = 0.047). The penetrance of BRCA1/2 alterations in our cohort seems to be aligned with other published results. However, new data interpretations have emerged in relation to the clinical criteria and the presence of deleterious mutations. This information shows that a correct and accurate clinical selection could avoid unnecessary molecular tests and could better address genetic analysis and clinical management.