BRCA1/2 mutation carriers have an increased risk for breast cancer (BC), ovarian cancer (OC), prostate cancer and pancreatic cancer (PC). On this basis, the NCCN Guidelines include prostate and PC among the BRCA testing criteria. In our Institution, BRCA diagnostic test is exclusively offered to patients affected by BC or OC, according to the Modena criteria, or to healthy women with BRCAPro> 40%. The aim of this study was to compare the rate of positive BRCA test in families with PC, classified according to NCCN guidelines or Modena criteria.
We retrospectively analyzed families with family history of PC registered in the archive of our Family Cancer Clinic. Analysis of BRCA1/2 mutation was evaluated in these families and the BRCA mutation detection rate was calculated according to both selection criteria. We also evaluated age at diagnosis and overall survival of patients affected by PC.
435 families with at least one diagnosis of PC have been identified. 393 families had PC and BC and/or OC cases and were included in our analysis. 55.5% of these families were candidate to BRCA testing according to the Modena Criteria, whereas 90.8% of families were candidate according to the NCCN Guidelines. 65.6% of families selected according with the Modena Criteria underwent BRCA test, identifying 19 BRCA1 mutations and 16 BRCA2 mutations (detection rate 24.5%). 45.9% of families with the NCCN Criteria underwent the test with the identification of the same mutations (detection rate 21.3%). Mean age at PC diagnosis was lower in patients with family history of BC and/or OC (65.8 years) and in BRCA mutated families (65.7 years) than in general population (72 years). One-year OS rate was higher in patients with family history of BC and/or OC (41.3%) and in BRCA mutated families (50%) than in general population (23%). 5-year OS was around 5% for patients with family history or BRCA mutation in the family and general population.
Our retrospective study confirms the high rate of positive BRCA1/2 test in families with PC associated to BC and/or OC. The NCCN Guidelines compared to the Modena Criteria did not increase the BRCA mutation detection rate. Notably, PC diagnosed in families with history of BC and/or OC or BRCA mutation showed younger age at diagnosis and better 1-year OS. We are planning to test all the remaining families selected by NCCN guidelines.
Clinical trial identification
Legal entity responsible for the study
Dr. Laura Cortesi
All authors have declared no conflicts of interest.