Women with hereditary BRCA1/2 mutations have an increased lifetime risk of developing breast cancer and ovarian cancer. With increased availability and affordability of testing, more women are being informed that they are mutation carriers. It is therefore critical to counsel them correctly as to their risk of developing these diseases and the timing of risk-reducing interventions such as surgery.
A large prospective cohort study of BRCA1/2 mutation carriers evaluated the impact of mutation type, location, and family history on the incidence and risk of breast, ovarian, and contralateral breast cancer. Analysis of 6030 BRCA1 female carriers revealed a rapid increase in the incidence of breast cancer until age 30 to 40, which stabilized until age 80, resulting in a 72% cumulative risk of breast cancer in BRCA1 carriers. Analysis of 3820 BRCA2 carriers revealed an increasing incidence of breast cancer until age 40 to 50, which stabilizes through age 80, leading to a 69% cumulative risk of breast cancer in BRCA2 carriers. For BRCA1 and BRCA2 carriers up to 80 years of age, the cumulative risk of ovarian cancer was 44% and 17%, respectively, and the cumulative risk of contralateral breast cancer was 40% and 26%, respectively. There was a significant trend between the number of close relatives diagnosed with breast cancer and increased risk.
The study highlights the importance of mutation location and family history during risk assessment of breast cancer patients. Being the most important finding that the risk reduction bilateral salpingo-oophorectomy should be approached differently in BRCA1 vs 2 patients, while bilateral prophylactic mastectomy recommendations should probably be similar regardless of the gene involved. Comprehensive family history and careful analysis of the mutation location are important and are best accomplished by utilizing genetic counselors in the result delivery discussion when surveillance and treatment decisions are being made. This study will aid the decision-making process for women identified as BRCA mutation carriers.
