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A Comparison of Bilateral Breast Cancers in BRCA Carriers

¹ Department of Clinical Cancer Genetics, City of Hope Cancer Center, Duarte, California; ² Department of Human Genetics and Medicine, Memorial-Sloan Kettering Cancer Center, New York, New York; ³ Istituto Nazionale Tumori, Milan, Italy; ⁴ Institut Curie, Paris, France; ⁵ Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska; ⁶ San Francisco Comprehensive Cancer Center, University of California, California; ⁷ Department of Medicine, Division of Medical Genetics and Department of Human Genetics, McGill University, Montreal, Quebec, Canada; ⁸ Department of Obstetrics and Gynecology, University of Vienna, Austria; ⁹ Beth Israel Deaconess Medical Center, Boston, Massachusetts; ¹⁰ Epidemiology Research Unit, Hôtel-Dieu de Montréal, Canada; ¹¹ Center for Clinical Cancer Genetics, University of Chicago, Illinois; ¹² Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC; ¹³ British Columbia Cancer Agency, Vancouver, British Columbia, Canada; ¹⁴ Unit of Medical Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital, Oslo, Norway; ¹⁵ Division of Epidemiology, Department of Medicine, University of California, Irvine, California; and ¹⁶ The Centre for Research in Women's Health, University of Toronto, Ontario, Canada

Requests for reprints: Steven A. Narod, The Centre for Research in Women's Health, 790 Bay Street, Toronto, Ontario, Canada M5G 1N8. Phone: 416-351-3765; Fax: 416-351-3767. E-mail steven.narod{at}sw.ca

Background: Women with breast cancer and a BRCA mutation have a high risk of developing a contralateral breast cancer. It is generally believed that the two cancers represent independent events. However, the extent of concordance between the first and second tumors with respect to hormone receptor expression and other pathologic features is unknown.

Purpose: To determine the degree of concordance of estrogen receptor (ER) status, tumor grade, and histology in tumors from women with bilateral breast cancer and a BRCA mutation.

Subjects and Methods: Women with a history of bilateral invasive breast cancers were selected from an international registry of women with BRCA1 or BRCA2 mutations. Medical records were reviewed to document the characteristics of each cancer and the treatments received.

Results: Data were available for 286 women with bilateral breast cancer and a BRCA mutation (211 BRCA1; 75 BRCA2). The mean interval between first and second tumor was 5.1 years. The two tumors were concordant more often than expected for ER status (P < 0.0001) and for grade (P < 0.0001), but not for histology (P = 0.55). The ER status of the first tumor was highly predictive of the ER status of the second tumor (odds ratio, 8.7; 95% confidence interval, 3.5-21.5; P < 0.0001). Neither age, menopausal status, oophorectomy nor tamoxifen use was predictive of the ER status of the second tumor.

Conclusions: There is strong concordance in ER status and tumor grade between independent primary breast tumors in women with a BRCA mutation. The excess concordance may be due to common risk factors, genetic variation, or the existence of a preneoplastic lesion that is common to both tumors.

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