Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers.
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.
Mitchell
Gillian
G
Translational Cancer Genetics Team, Institute of Cancer Research and Cancer Genetics Unit, Royal Marsden NHS Hospital, United Kingdom.
Antoniou
Antonis C
AC
Warren
Ruth
R
Peock
Susan
S
Brown
Judith
J
Davies
Russell
R
Mattison
Jenny
J
Cook
Margaret
M
Warsi
Iqbal
I
Evans
D Gareth
DG
Eccles
Diana
D
Douglas
Fiona
F
Paterson
Joan
J
Hodgson
Shirley
S
Izatt
Louise
L
Cole
Trevor
T
Burgess
Lucy
L
Eeles
Ros
R
Easton
Douglas F
DF
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