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Mammographic Density and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

EMBRACE collaborators, Ros Eeles¹, Douglas F. Easton³

¹ Translational Cancer Genetics Team, Institute of Cancer Research and Cancer Genetics Unit, Royal Marsden NHS Hospital, United Kingdom; ² Clinical Genetics Department, Guy's Hospital, London, United Kingdom; ³ Cancer Research UK Genetic Epidemiology Unit, Strangeways Research Laboratory, Department of Public Health and Primary Care, and ⁴ Department of Radiology, University of Cambridge; ⁵ Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, United Kingdom; ⁶ East Devon Breast Screening Program, Breast Care Unit, Royal Devon and Exeter Hospital, Exeter, United Kingdom; ⁷ Academic Unit of Medical Genetics and Regional Genetics Service, St. Mary's Hospital, Manchester, United Kingdom; ⁸ Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, United Kingdom; ⁹ Institute of Human Genetics, International Centre for Life, Central Parkway, Newcastle upon Tyne, United Kingdom; and ¹⁰ West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, United Kingdom

Requsests for reprints: Antonis C. Antoniou, Cancer Research UK Genetic Epidemiology Unit, Strangeways Research Laboratory, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, United Kingdom. Phone: 44-1223-740163; Fax: 44-1223-740159; E-mail: antonis{at}srl.cam.ac.uk.

High breast density as measured on mammograms is a strong risk factor for breast cancer in the general population, but its effect in carriers of germline BRCA1 and BRCA2 mutations is unclear. We obtained mammograms from 206 female carriers of BRCA1 or BRCA2 mutations, 96 of whom were subsequently diagnosed with breast cancer and 136 relatives of carriers who were themselves noncarriers. We compared the mammographic densities of affected carriers (cases) and unaffected carriers (controls), and of mutation carriers and noncarriers, using a computer-assisted method of measurement and visual assessment by two observers. Analyses were adjusted for age, parity, body mass index, menopausal status, and hormone replacement therapy use. There was no difference in the mean percent density between noncarriers and carriers. Among carriers, increasing mammographic density was associated with an increased risk of breast cancer (P_trend = 0.024). The odds ratio (OR; 95% confidence interval) for breast cancer associated with a density of 50% was 2.29 (1.23-4.26; P = 0.009). The OR did not differ between BRCA1 and BRCA2 carriers or between premenopausal and postmenopausal carriers. The results suggest that the distribution of breast density in BRCA1 and BRCA2 carriers is similar to that in non-carriers. High breast density in carriers is associated with an increased risk of breast cancer, with the relative risk being similar to that observed in the general population. Use of mammographic density could improve individual risk prediction in carriers. (Cancer Res 2006; 66(3): 1866-72)

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