Risk of Second Non Breast Malignancies (SNBM) in Relation to BRCA1 and BRCA2 Mutation Status Following Breast-Conserving Surgery and Radiotherapy

Abstract

Women from hereditary breast cancer families with BRCA1/2 germline mutation are at increased risk for contralateral breast cancer (BC) and for ovarian cancer (OC). It is less clear whether mutation status influences the rate of SNBM other than OC. In addition, little is known on the risk of OC in individuals from hereditary BC families without identified BRCA mutation. Our purpose was to answer to these two questions. We retrospectively analysed a cohort of women with small cancers treated with breast conserving surgery and radiotherapy at our Institut from 1981 to 2000. The studied population was matched using strict criteria. BRCA1/2 carriers had more SNBM than the French women population (FWP) (SIR=1099.2 [354.3-2565.4], p<10-3); there were no differences between non carriers or controls and the FWP (SIR=149.3 [30.0-436.2] and SIR=80 [21.5-204.7], respectively). The BRCA1/2 carriers and non carriers had more OC than the FWP (SIR=9640.1 [2593.6-24680.6]; p<10-3 and SIR=1155.7 [129.8-4172.6]; p<0.05, respectively). We did not find any differences between the incidence rates of digestive, gynaecological and lung carcinoma between controls and the FWP, between BRCA1/2 carriers and the FWP; and between non carriers and the FWP. After 9 year follow-up, our study showed that the rate of OC was increased in BRCA1/2 mutation carriers as well as in non carriers compared to the FWP. We also showed that these patients were not at higher risk of SNBM other than OC. No differences have been found in the incidence rates of SNBM other than OC between controls and the FWP, between BRCA1/2 carriers, non carriers and the general population, but more statistical power is needed to confirm these results.