Familial invasive breast cancers: Worse outcome related to BRCA1 mutations

Purpose: Although all studies confirm that BRCA1 tumors are highly prolifer ative and poorly differentiated, their outcomes remain controversial. We pr opose to examine, through a cohort study, the pathologic characteristics, o verall survival, local recurrence, and metastasis-free intervals of 40 pati ents with BRCA1 breast cancer. Patients and Methods: A cohort of 183 patients with invasive breast cancer, treated at the Institut Curie and presenting with a familial history of br east and/or ovarian cancer, were tested for BRCA1 germ-line mutation. Tumor characteristics and clinical events were extracted from our prospectively registered database. Results: Forty BRCA1 mutations were found among the 183 patients (22%). Med ian follow-up was 58 months. BRCA1 tumors were larger in size (P =.03), had a higher rate of grade 3 histoprognostic factors (P =,002), and had a high er frequency of negative estrogen (P =.003) and progesterone receptors (P = .002) compared with non-BRCA1 tumors. Overall survival was poorer for carri ers than for noncarriers (5-year rate, 80% v 91%, P =.002), Because a long time interval between cancer diagnosis and genetic counseling artificially increases survival time due to unrecorded deaths, the analysis was limited to the 110 patients whose diagnosis-to-counseling interval war less than 36 months (19 BRCA1 patients and 91 non-BRCA1 patients), The differences betw een the BRCA1 and non-BRCA1 groups regarding overall survival and metastasi s-free interval were dramatically increased (49% v 85% and 18% v 84%, respe ctively). Multivariate analysis showed that BRCA1 mutation was an independe nt prognostic factor. Conclusion: Our results strongly support that among patients with familial breast cancer, those who have a BRCA1 mutation have a worse outcome than th ose who do not. J Clin Oncol 18:4053-4059. (C) 2000 by American Society of Clinical Oncology.