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.
Gierach
Gretchen L
GL
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
Loud
Jennifer T
JT
Chow
Catherine K
CK
Prindiville
Sheila A
SA
Eng-Wong
Jennifer
J
Soballe
Peter W
PW
Giambartolomei
Claudia
C
Mai
Phuong L
PL
Galbo
Claudia E
CE
Nichols
Kathryn
K
Calzone
Kathleen A
KA
Vachon
Celine
C
Gail
Mitchell H
MH
Greene
Mark H
MH
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