Mammographic breast density is a strong predictor of breast cancer. The current retrospective study determines if the direction and degree of the association between risk factors for breast density and the breast density phenotype differ in the subsets of women stratified by menopausal status, hormone replacement therapy use (HRT), and family history of breast cancer.
The study participants were selected from women enrolled in the Fernald Medical Monitoring Program (FMMP). To be included in the study, women were required to have been enrolled in FMMP as adults, be Caucasians, and have had at least one mammogram in FMMP mammography database. Women who had any diagnosis of breast cancer, genetic syndromes and disorders with underdevelopment of breast and small stature, history of mammoplasty, or were transsexual were not eligible for the study. Discordant phenotypes for mammographic breast density (high breast density [cases, N=265] and low breast density [controls, N=860]) were defined using the mammographic breast density assessment from the original radiologists’ readings. The earliest FMMP screening or diagnostic mammogram that had criteria used to define the density phenotype was used as an index mammogram if the woman was 40-80 years old at the time of the index mammogram and had a Body Mass Index (BMI)<35 at the time of the mammogram. The data were analyzed using SAS Statistical Software.
Findings of this study suggested a statistically significant effect of parity (protective) and alcohol use (direct) on breast density. A significant effect of age on breast density was limited to 50-<60 year old women. When stratified by menopausal status, BMI showed a significant protective effect and ever use of alcohol showed a significant direct effect on breast density phenotype in premenopausal women, while in postmenopausal women, parity showed a significant protective effect and a family history of breast cancer, age, and HRT use had direct effects on the breast density phenotype. In women who never used HRT, age and BMI showed a significant protective effect. When stratified by any family history of breast cancer, ever use of alcohol (direct effect) and parity (protective effect) were the only predictors of the breast density status and their effect was stronger in women with a family history of breast cancer compared to women without a family history of breast cancer.
Findings of the study suggested that BMI, parity, use of hormone replacement therapy, and ever use of alcohol appear to be the most important predictors of the breast density phenotype in different subsets of women stratified based on their menopausal status, history of HRT use, and a family history of breast cancer. The results also suggested that different strength of the effect of parity and alcohol on breast density in women with and without a family history of breast cancer could be the result of gene-environment interactions. A subset analysis on 180 women for the effects of several single nucleotide polymorphisms (SNPs) in the estrogen metabolism pathway genes on the breast density phenotype is underway.