Breast Density, Body Mass Index, and Risk of Tumor Marker-Defined Subtypes of Breast Cancer

Abstract

Breast density and body mass index (BMI) are correlated attributes and are both potentially modifiable risk factors for breast cancer. However, relationships between these factors and risk of molecularly-defined subtypes of breast cancer have not been established. We used breast density and BMI data collected by the Breast Cancer Surveillance Consortium from 1,054,466 women ages 40 to 84 years receiving mammography, including 13,797 women subsequently diagnosed with breast cancer. Cases were classified into three groups on the basis of expression of the estrogen receptor (ER), progesterone receptor (PR), and HER2:1) ER-positive (ER+, n = 10,026), 2) HER2-expressing (ER-negative/PR-negative/HER2-positive, n = 308), or triple-negative (ER-negative/PR-negative/HER2-negative, n = 705). Using Cox regression, we evaluated subtype-specific associations with breast density and BMI. Breast density was similarly positively associated with risk of all subtypes, especially among women ages 40 to 64 years. BMI was positively associated with risks of ER+ and triple-negative breast cancer in women ages 50 to 84 who were not users of hormone therapy. Breast density is positively associated with breast cancer risk, regardless of disease subtype. Associations with BMI appear to vary more by breast cancer subtype. Additional studies are needed to confirm and further characterize risk factors for HER2-expressing and triple-negative breast cancer.