Associations of reproductive history with serum and intratumoral sex steroid hormone levels among postmenopausal women with breast cancer: Analysis of paired serum and tumor tissue samples

BACKGROUND: Intratumoral estrogens may contribute to the growth of breast cancer. Risk factors for breast cancer, including reproductive factors, may influence intratumoral hormone levels. METHODS: This cross-sectional study of 146 postmenopausal women with breast cancer investigated associations of reproductive factors, including parity and breastfeeding history, with serum and intratumoral (tissue) hormone levels, as well as aromatase activity, by hormone receptor subtype classified as estrogen receptor-positive or estrogen receptor-negative and progesterone receptor-negative, using analysis of covariance. Hormone levels and aromatase activity in paired serum and tumor tissue samples were measured using liquid chromatography-tandem mass spectrometry and the tritiated water-release assay. Epidemiological data were collected through a self-administered questionnaire. FINDINGS: Among women with estrogen receptor-positive cancer, parity history (nulliparous vs. parous) was not significantly associated with serum or tissue hormone levels. No linear association was observed between parity number (nulliparous, 1, 2, ≥3) and tissue estradiol levels (age- and stage-adjusted means: 109.2, 76.7, 85.9, and 113.2 pg/g, respectively; p = 0.58). Tissue estradiol levels were significantly higher among parous women with breastfeeding history (age- and stage-adjusted mean: 103.2 pg/g) than among those without (64.5 pg/g, p = 0.01). In estrogen receptor-negative and progesterone receptor-negative cancers, no associations were observed between these reproductive factors and hormone levels or aromatase activity. CONCLUSIONS: Reproductive history, particularly breastfeeding, may be associated with intratumoral estradiol levels in postmenopausal women with estrogen receptor-positive breast cancer. These findings suggest the importance of considering reproductive factors when investigating biological mechanisms underlying breast cancer progression and prognosis.