Abstract
BACKGROUND: It remains unknown if later life breast cancer risk as determined by reproductive history is mediated by postmenopausal breast density and/or sex steroid levels. METHODS: Increased breast density is a strong surrogate for future breast cancer risk. A cross-sectional study with a longitudinal follow up for breast health outcomes evaluated women without breast cancer (n = 1,023; 682 = parous), drawn from a high risk postmenopausal population, with questionnaire reported reproductive histories. The questionnaire was linked to prospective screening mammogram breast density measurements, and saliva biospecimens that were used to assess sex steroid hormone levels. RESULTS: Expected age and postmenopause related declines in salivary estradiol (E), progesterone (P), dehydroepiandrosterone (DHEA) and testosterone (T) levels were observed. This was most pronounced for DHEA and T, which were also the only postmenopausal hormone levels significantly associated with any reproductive characteristics: parity and breast feeding for DHEA, age-at-first birth for T. Postmenopausal breast density was borderline significantly lower with parity and higher body mass index (BMI). After multivariate analysis, T was the only hormone level to retain any association (negative, p<0.05) with breast density. CONCLUSIONS AND GENERAL SIGNIFICANCE: While reproductive characteristics, in particular parity, generally demonstrated independent associations with postmenopausal breast density and E, P and DHEA levels, T levels showed concordant inverse associations with age-at-first birth and breast density. These findings suggest that reproductive effects and later life salivary sex steroid hormone levels may have independent effects on later life breast density and cancer risk.