title: Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers.
abstract: 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 > or =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.
authors.affiliation: Translational Cancer Genetics Team, Institute of Cancer Research and Cancer Genetics Unit, Royal Marsden NHS Hospital, United Kingdom.
authors.forename: Gillian
authors.initials: G
authors.lastname: Mitchell
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Ruth
authors.initials: R
authors.lastname: Warren
authors.forename: Susan
authors.initials: S
authors.lastname: Peock
authors.forename: Judith
authors.initials: J
authors.lastname: Brown
authors.forename: Russell
authors.initials: R
authors.lastname: Davies
authors.forename: Jenny
authors.initials: J
authors.lastname: Mattison
authors.forename: Margaret
authors.initials: M
authors.lastname: Cook
authors.forename: Iqbal
authors.initials: I
authors.lastname: Warsi
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Diana
authors.initials: D
authors.lastname: Eccles
authors.forename: Fiona
authors.initials: F
authors.lastname: Douglas
authors.forename: Joan
authors.initials: J
authors.lastname: Paterson
authors.forename: Shirley
authors.initials: S
authors.lastname: Hodgson
authors.forename: Louise
authors.initials: L
authors.lastname: Izatt
authors.forename: Trevor
authors.initials: T
authors.lastname: Cole
authors.forename: Lucy
authors.initials: L
authors.lastname: Burgess
authors.forename: Ros
authors.initials: R
authors.lastname: Eeles
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
mesh_terms: D000328:Adult; D001940:Breast / Q000033:anatomy & histology*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008327:Mammography; D008875:Middle Aged