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Late Toxicity Is Not Increased in BRCA1/BRCA2 Mutation Carriers Undergoing Breast Radiotherapy in the United Kingdom

Authors' Affiliations: ¹ Institute of Cancer Research and Royal Marsden NHS Foundation Trust, ² Department of Medical Genetics, 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 Familial Cancer Service, Westmead Hospital, Sydney, Australia; ⁷ Division of Genetic Medicine, Vanderbilt University, Nashville, Tennessee; ⁸ Birmingham Oncology Centre, University Hospitals NHS Trust, Birmingham, United Kingdom; ⁹ Academic Unit of Medical Genetics and Regional Genetics Services, St. Mary's Hospital; ¹⁰ Christie Hospital, Withington, Manchester, United Kingdom; ¹¹ Princess Anne Hospital, Wessex Regional Genetics Centre, ¹² Department of Surgery, Royal South Hants Hospital, Southampton, United Kingdom; ¹³ Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; and ¹⁴ Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom

Requests for reprints: Susan Shanley, Cancer Genetics Unit, Orchard House, Royal Marsden NHS Foundation Trust, Downs Road, Sutton SM2 5PT, United Kingdom. Phone: 44-208-661-3375; Fax: 44-208-7770-1489; E-mail: Susan.Shanley{at}rmh.nhs.uk.

Purpose: To undertake the first substantial clinical study of breast radiotherapy toxicity in BRCA1 and BRCA2 mutation carriers in the United Kingdom.

Experimental Design: Acute and late radiation effects were evaluated in a retrospective study of 55 BRCA1 and BRCA2 mutation carriers treated with radiotherapy for breast cancer at four centers between 1983 and 2002. Individual matching with controls who had sporadic breast cancer was undertaken for age at diagnosis, time since completion of radiation, and treatment variables. Detailed assessments were undertaken by one examiner. Median follow-up was 6.75 years for carriers and 7.75 years for controls. Rates of late events (rib fractures, lung fibrosis, necrosis of soft tissue/bone, and pericarditis) as well as LENT-SOMA scores and clinical photography scores of breast size, shape, and skin telangiectasia were the primary end points.

Results: No increase in clinically significant late toxicity was seen in the mutation carriers.

Conclusions: These data add substantial weight to the evidence that the outcomes in the treated breast from radiotherapy in women with BRCA1 or BRCA2 mutations are comparable with those in women with sporadic breast cancer.

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