Familial Invasive Breast Cancers: Worse Outcome Related to BRCA1 Mutations

• Published in: Journal of clinical oncology Vol. 18; no. 24; pp. 4053 - 4059
• Main Authors: STOPPA-LYONNET, Dominique, ANSQUER, Yan, FOURQUET, Alain, ASSELAIN, Bernard, DREYFUS, Helene, GAUTIER, Chantal, GAUTHIER-VILLARS, Marion, BOURSTYN, Edwige, CLOUGH, Krishna B, MAGDELENAT, Henri, POUILLART, Pierre, VINCENT-SALOMON, Anne
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 15-12-2000; Lippincott Williams & Wilkins
• Subjects: Adult; Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cohort Studies; Disease-Free Survival; Family Health; Female; Follow-Up Studies; Genes, BRCA1 - genetics; Germ-Line Mutation; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Proportional Hazards Models; Survival Rate; Treatment Outcome; Tumors; Human; Mammary gland diseases; Prognosis; Genetics; Familial cancer; Mammary gland; Mutation; Malignant tumor; Tumor suppressor gene
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2000.18.24.4053

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.
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.
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.
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.