Mammographic density does not differ between unaffected BRCA1/2 mutation carriers and women at low-to-average risk of breast cancer.
Elevated mammographic density (MD) is one of the strongest risk factors for sporadic breast cancer. Epidemiologic evidence suggests that MD is, in part, genetically determined; however, the relationship between MD and BRCA1/2 mutation status is equivocal. We compared MD in unaffected BRCA1/2 mutation carriers enrolled in the U.S. National Cancer Institute's Clinical Genetics Branch's Breast Imaging Study (n = 143) with women at low-to-average breast cancer risk enrolled in the same study (n = 29) or the NCI/National Naval Medical Center's Susceptibility to Breast Cancer Study (n = 90). The latter were BRCA mutation-negative members of mutation-positive families or women with no prior breast cancer, a Pedigree Assessment Tool score <8 (i.e., low risk of a hereditary breast cancer syndrome) and a Gail score <1.67. A single experienced mammographer measured MD using a computer-assisted thresholding method. We collected standard breast cancer risk factor information in both studies. Unadjusted mean percent MD was higher in women with BRCA1/2 mutations compared with women at low-to-average breast cancer risk (37.3% vs. 33.4%; P = 0.04), but these differences disappeared after adjusting for age and body mass index (34.9% vs. 36.3%; P = 0.43). We explored age at menarche, nulliparity, age at first birth, menopausal status, number of breast biopsies, and exposure to exogenous hormonal agents as potential confounders of the MD and BRCA1/2 association. Taking these factors into account did not significantly alter the results of the age/body mass index-adjusted analysis. Our results do not provide support for an independent effect of BRCA1/2 mutation status on mammographic density.
Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. gierachg@mail.nih.gov
Gretchen L
GL
Gierach
Jennifer T
JT
Loud
Catherine K
CK
Chow
Sheila A
SA
Prindiville
Jennifer
J
Eng-Wong
Peter W
PW
Soballe
Claudia
C
Giambartolomei
Phuong L
PL
Mai
Claudia E
CE
Galbo
Kathryn
K
Nichols
Kathleen A
KA
Calzone
Celine
C
Vachon
Mitchell H
MH
Gail
Mark H
MH
Greene
D000328:Adult; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008327:Mammography; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors