SHBG and breast cancer: In a study of healthy premenopausal women, Emaus et al. [34] and Verkasalo et al. [70] found that higher levels of physical activity were associated with lower circulating estradiol (E2) levels; additionally, both physical activity and heart rate were linked to a metabolic risk score, which in turn was associated with daily E2 levels, suggesting key biological pathways connecting sedentary behavior to increased BC risk [34], while decreasing BMI was found to increase SHBG [70].