Journal of Clinical Oncology, Vol 18, Issue 24
(December), 2000: 4053-4059
© 2000 American Society for Clinical Oncology
Familial Invasive Breast Cancers: Worse Outcome Related to BRCA1 Mutations
By Dominique Stoppa-Lyonnet,
Yan Ansquer,
Hélène Dreyfus,
Chantal Gautier,
Marion Gauthier-Villars,
Edwige Bourstyn,
Krishna B. Clough,
Henri Magdelénat,
Pierre Pouillart,
Anne Vincent-Salomon,
Alain Fourquet,
Bernard Asselain,
for the Institut Curie Breast Cancer Group
From the Departments of Oncology Genetics, Biostatistics, Radiotherapy, Surgery, Pharmacology, Medical Oncology, and Pathology, Institut Curie, Paris, France.
Address reprint requests to Dominique Stoppa-Lyonnet, MD, PhD, Service de Génétique Oncologique, Institut Curie, 26 Rue d’Ulm, F75248 Paris, France; email dominique.lyonnet{at}curie.net
PURPOSE: Although all studies confirm that BRCA1 tumors are highly proliferative and poorly differentiated, their outcomes remain controversial. We propose to examine, through a cohort study, the pathologic characteristics, overall survival, local recurrence, and metastasis-free intervals of 40 patients 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 breast 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%). Median 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 higher frequency of negative estrogen (P = .003) and progesterone receptors (P = .002) compared with non-BRCA1 tumors. Overall survival was poorer for carriers 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 was less than 36 months (19 BRCA1 patients and 91 non-BRCA1 patients). The differences between the BRCA1 and non-BRCA1 groups regarding overall survival and metastasis-free interval were dramatically increased (49% v 85% and 18% v 84%, respectively). Multivariate analysis showed that BRCA1 mutation was an independent 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 those who do not.
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