Genetic testing of breast and ovarian cancer patients: clinical characteristics and hormonal risk modifiers

Objectives: Carriers of the mutations 185delAG and 5382insC in the BRCA1 ge ne and 6174delT in the BRCA2 gene have a substantial life-time risk for bre ast and ovarian cancers (BC and OC). The aim of the study was to identify t he clinical features and the hormonal risk modifiers in mutation carriers a nd the implication in suggested guidelines for treatment decisions in BRCA1 /2 carrier patients. Study design: Breast and/or ovarian cancer patients fr om the Oncology and Cancer Genetic clinics were tested for the three Ashken azi founder mutations: 87 patients were identified as carriers of one of th ese mutations. Clinical presentation and age at onset were correlated with the mutations, in patients with bilateral BC or BC and OC, the length of ti me that elapsed between the diagnosis of the two cancers was recorded. We c ompared BC and OC patients with regard to ages at menarche, first pregnancy and menopause, number of pregnancies and deliveries, the use of oral contr aceptives, hormonal replacement therapy and fertility treatments. Results: The carriers of the three BRCA1/2 Ashkenazi founder mutations did not diffe r in clinical presentation nor age at onset. Forty-three patients (74.1%) o f 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 afte r age 35. Ovarian cancer was diagnosed after age 45 in 89.7% of the patient s, 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 patie nts, Other hormonal factors did not differ between the two groups. Conclusi ons: The carriers of the three Ashkenazi founder mutations should be consid ered 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 ve ry high risk for developing second breast cancer. Most ovarian cancers in c arriers were diagnosed after age 45, and prophylactic oophorectomy should b e postponed to the age of 45. Oral contraceptives might elevate the risk of BC in mutation carriers. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.