Linking physical activity to breast cancer via sex steroid hormones Part 2: The effect of sex steroid hormones on breast cancer risk

We undertook a systematic review and appraised the evidence for an effect of circulating sex steroid hormones and sex hormone binding globulin (SHBG) on breast cancer risk in pre- and post-menopausal women. Systematic searches identified prospective studies relevant to this review. Meta-analyses estimated breast cancer risk for women with the highest compared to the lowest level of sex hormones and the DRMETA Stata package was used to graphically represent the shape of these associations. The ROBINS-E tool assessed risk of bias, and the GRADE system appraised the strength of evidence.In pre-menopausal women, there was little evidence that estrogens, progesterone or SHBG were associated with breast cancer risk, whereas androgens showed a positive association. In post-menopausal women, higher estrogens and androgens were associated with an increase in breast cancer risk, whereas higher SHBG was inversely associated with risk. The strength of the evidence quality ranged from low to high for each hormone. Dose-response relationships between sex steroid hormone concentrations and breast cancer risk were most notable for post-menopausal women. These data support the plausibility of a role for sex steroid hormones in mediating the causal relationship between physical activity and the risk of breast cancer.