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Acute Chemotherapy–Related Toxicity Is Not Increased in BRCA1 and BRCA2 Mutation Carriers Treated for Breast Cancer in the United Kingdom

Authors' Affiliations: ¹ Institute of Cancer Research and Royal Marsden NHS Foundation Trust; ² Department of Medical Genetics and ³ Oncology Unit, Guy's and St. Thomas NHS Foundation Trust; ⁴ St. George's Hospital Medical School and St. George's Hospital; ⁵ Gray Cancer Institute, Northwood, London, United Kingdom; ⁶ Division of Genetic Medicine, Vanderbilt University, Nashville, Tennessee; ⁷ Birmingham Oncology Centre, University Hospitals NHS Trust, Birmingham, United Kingdom; ⁸ Academic Unit of Medical Genetics and Regional Genetics Services, St. Mary's Hospital; ⁹ Christie Hospital, Withington, Manchester, United Kingdom; ¹⁰ Princess Anne Hospital, Wessex Regional Genetics Centre; ¹¹ Department of Surgery, Royal South Hants Hospital, Southampton, United Kingdom; ¹² Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; and ¹³ Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom

Requests for reprints: Susan Shanley, Cancer Genetics Unit, Royal Marsden NHS Foundation Trust, Downs Road, Sutton SM2 5PT, United Kingdom. Phone: 44-208-661-3375; Fax: 44-208-770-1489; E-mail: shanleysusan{at}hotmail.com.

Purpose: To evaluate acute toxicity induced by chemotherapy for breast cancer in a retrospective study of 62 BRCA1/2 mutation carriers matched 1:1 with women who had treatment for sporadic disease in the United Kingdom between 1983 and 2003.

Experimental Design: All participants were interviewed by one of two researchers using standardized questionnaires, and their medical records were reviewed by one research nurse. The two main regimens received were cyclophosphamide, methotrexate, and fluorouracil and fluorouracil, epirubicin, and cyclophosphamide. The proportion of cases and controls receiving anthracycline-based treatment was equivalent, but fewer BRCA1 cases received this treatment than did BRCA2 mutation carriers. Toxicity was documented using the Eastern Cooperative Oncology Group Common Toxicity Criteria for hematologic, infective, and gastrointestinal toxicities. No increase in toxicity was seen in BRCA1/2 mutation carriers.

Results: The only significant difference was that neutropenia was less evident in BRCA2 mutation carriers than in either BRCA1 mutation carriers or controls. As a result, there was no requirement for dose reduction among BRCA2 mutation carriers, in contrast to 10 of 39 BRCA1 carriers and 16 of 62 controls (P = 0.02).

Conclusions: This result has implications for therapy and indicates that women with mutations in BRCA1 and BRCA2 may be given the same doses of chemotherapy as noncarriers.

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