Clinical course of breast cancer in carriers of BRCA1 germline mutations

Purpose: To compare clinical prognosis of breast cancer in three different groups of patients: 46 BRCA1 mutation carriers (BRCA1+), 46 BRCA1 mutation non-carriers (BRCA1-), and 48 patients, who never had genetic counselling (CG).
Material and methods: Patients were treated for breast cancer in the Center of Oncology in Gliwice between 1972 and 2002. Local recurrence rate (RFS), metastases free survival (MFS), incidence of second cancer, disease-free survival (DFS) and overall survival (OS) were analysed using Cox model. Results: The actuarial 10-year RFS was 95% in BRCA1+ group and was significantly higher than in BRCA1- and CG groups (71% and 50%, respectively). The corresponding 10-year metastases-free survival in BRCA1+, BRCA1- and CG groups was 82%, 67% and 49% respectively. A remarkably high incidence of second breast cancer in BRCA1+ and BRCA1- groups (46% and 50%) compared to 2% in the control group can be attributed to counseling criteria. 10 patients from BRCA1+ group developed ovarian cancer compared to only 1 in BRCA1- group and 0 in CG group. The actuarial 10-year overall survival was significantly higher in BRCA1+ and BRCA1- groups (78.5% and 80%, respectively) as compared to the control group (32%).
Conclusions: The overall survival of BRCA1 mutation carriers did not differ significantly from non-carriers due to frequent occurrence of hereditary ovarian cancers that eventually remained loco-regionally uncontrolled. Patients with sporadic breast cancer presented in the most advanced stages, and carried the most unfavorable prognosis. This shows that the counseling itself may carry the bias of artificially increasing survival times by excluding patients with the most advanced disease at the diagnosis.