© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 24, 2112-2117,
December 15, 1999
© 1999 Oxford University Press
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Breast Conservation Therapy for Invasive Breast Cancer in Ashkenazi Women With BRCA Gene Founder Mutations
Affiliations of authors: M. Robson, K. Offit (Departments of Human Genetics and Medicine), D. Levin (Department of Human Genetics), M. Federici, F. Bogolminy, A. Heerdt, P. Borgen (Department of Surgery), J. Satagopan (Department of Epidemiology and Biostatistics), B. McCormick (Department of Radiation Oncology), C. Hudis, L. Norton (Department of Medicine), J. Boyd (Departments of Human Genetics and Surgery), Memorial Sloan-Kettering Cancer Center, New York, NY.
Correspondence to: Mark Robson, M.D., Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021 (e-mail:robsonm{at}mskcc.org).
BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of breast cancer. Whether women with breast cancer who have inherited mutations in these genes have a different outcome after breast conservation therapy than women with "sporadic" cancer is unresolved. Consequently, we compared the outcomes after breast conservation therapy in Ashkenazi women with or without germline mutations in BRCA1 and/or BRCA2 (hereafter called BRCA). METHODS: We studied 305 women of Ashkenazi Jewish descent undergoing breast-conserving treatment for 329 invasive breast cancers. We reviewed their clinical records, retrieved their archival tissue samples, and tested those samples for the founder mutations BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. Genetic results were linked to clinical data and outcomes by univariate and multivariate analyses. All Pvalues are two-sided. RESULTS: We detected mutations in BRCA genes in 28 of 305 women. Women with BRCA mutations were more likely to be diagnosed with cancer before the age of 50 years (P<.001) and to have lymph node involvement (P = .04). Ipsilateral breast tumor recurrence was more common in women with BRCA mutations, although this did not reach statistical significance (relative risk [RR] = 1.79; 95% confidence interval [CI] = 0.64-5.03). Women with mutations were more likely to develop contralateral breast cancer (RR = 3.50; 95% CI = 1.78-8.74; P = .001). Distant disease-free survival was shorter in women with mutations (66.2% versus 84.3% at 10 years; P = .05), as was breast cancer-specific survival (71.9% versus 87.2% at 10 years; P = .02). Tumor stage and nodal status, but not mutation status, were predictive of distant disease-free and breast cancer-specific survival in multivariate analysis. CONCLUSIONS: Women with BRCA founder mutations are at increased risk for breast cancer-related events after breast conservation. However, mutation status is not an independent predictor of survival and should not influence decisions regarding adjuvant therapy. The increased contralateral breast cancer risk in women heterozygous for BRCA mutations mandates careful surveillance.
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