Hormonal alterations distinguishing high-risk women from breast cancer patients across the menopause transition

Hormonal level changes during the menopause transition have been proposed to influence breast cancer risk. Epidemiologic studies indicate that postmenopausal women with higher circulating estrogen levels are at an increased risk of developing breast cancer, suggesting that alterations in hormone profiles may reflect disease progression. However, few studies have investigated hormonal differences between high-risk women and those with active cancer. In this study, we measured 11 common hormones in plasma samples from 206 women, including 80 diagnosed with breast cancer and 126 high-risk but cancer-free women. We found that plasma levels of estrone (E1), estradiol (E2), deoxycorticosterone (DOC), and progesterone (PROG) were significantly lower in premenopausal breast cancer patients compared to high-risk women. Correlation analyses revealed that E1 levels were positively associated with body mass index (BMI) in postmenopausal high-risk individuals, while E2 levels showed a similar positive correlation in postmenopausal cancer patients. In contrast, BMI was negatively correlated with cortisol, testosterone, and 17alpha-deoxypregnenolone in postmenopausal high-risk women. These findings suggest that hormonal alterations, specificially reduced levels of E1, E2, DOC, and PROG, distinguish premenopausal high-risk women from those with active breast cancer. The menopause-dependent changes in hormone-BMI associations indicate that metabolic-hormonal interactions may drive the transition from cancer susceptibility to malignancy.