Abstract
BACKGROUND: Breast density is a strong risk factor for breast cancer and reflects epithelial and stromal content. Breast tissue is particularly sensitive to hormonal stimuli before it fully differentiates following the first full-term pregnancy. Few studies have examined associations between sex hormones and breast density among young women. METHODS: We conducted a cross-sectional study among 180 women ages 25 to 29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-up Study. Eighty-five percent of participants attended a clinic visit during their luteal phase of menstrual cycle. Magnetic resonance imaging measured the percentage of dense breast volume (%DBV), absolute dense breast volume (ADBV), and absolute nondense breast volume (ANDBV). Multiple-linear mixed-effect regression models were used to evaluate the association of sex hormones and sex hormone-binding globulin (SHBG) with %DBV, ADBV, and ANDBV. RESULTS: Testosterone was significantly positively associated with %DBV and ADBV. The multivariable geometric mean of %DBV and ADBV across testosterone quartiles increased from 16.5% to 20.3% and from 68.6 to 82.3 cm(3), respectively (Ptrend ≤ 0.03). There was no association of %DBV or ADBV with estrogens, progesterone, non-SHBG-bound testosterone, or SHBG (Ptrend ≥ 0.27). Neither sex hormones nor SHBG was associated with ANDBV except progesterone; however, the progesterone result was nonsignificant in analysis restricted to women in the luteal phase. CONCLUSIONS: These findings suggest a modest positive association between testosterone and breast density in young women. IMPACT: Hormonal influences at critical periods may contribute to morphologic differences in the breast associated with breast cancer risk later in life.