RESUMO
OBJECTIVES: Carriers of the mutations 185delAG and 5382insC in the BRCA1 gene and 6174delT in the BRCA2 gene have a substantial life-time risk for breast and ovarian cancers (BC and OC). The aim of the study was to identify the clinical features and the hormonal risk modifiers in mutation carriers and the implication in suggested guidelines for treatment decisions in BRCA1/2 carrier patients. STUDY DESIGN: Breast and/or ovarian cancer patients from the Oncology and Cancer Genetic clinics were tested for the three Ashkenazi founder mutations: 87 patients were identified as carriers of one of these mutations. Clinical presentation and age at onset were correlated with the mutations, in patients with bilateral BC or BC and OC, the length of time that elapsed between the diagnosis of the two cancers was recorded. We compared BC and OC patients with regard to ages at menarche, first pregnancy and menopause, number of pregnancies and deliveries, the use of oral contraceptives, hormonal replacement therapy and fertility treatments. RESULTS: The carriers of the three BRCA1/2 Ashkenazi founder mutations did not differ in clinical presentation nor age at onset. Forty-three patients (74.1%) of 58 BC patients were diagnosed between the ages 30 and 50, only four (6.9%) patients were diagnosed after age 60. Of BC patients diagnosed before age 35, 63.6% developed second BC as compared to 25.5% of those diagnosed after age 35. Ovarian cancer was diagnosed after age 45 in 89.7% of the patients, only one patient was diagnosed under the age of 40. Oral contraceptives use was documented in 61.3% of BC patients as compared to 11.8% of OC patients. Other hormonal factors did not differ between the two groups. CONCLUSIONS: The carriers of the three Ashkenazi founder mutations should be considered at the same risk for BC and for OC and treatment options should be the same. Mutation carriers diagnosed with BC before the age of 35 are at a very high risk for developing second breast cancer. Most ovarian cancers in carriers were diagnosed after age 45, and prophylactic oophorectomy should be postponed to the age of 45. Oral contraceptives might elevate the risk of BC in mutation carriers.