Convincing evidence now supports a probable preventive role for physical activity in postmenopausal
breast cancer. The mechanisms by which long-term physical activity affect risk, however, remain unclear. The aims of this review were to propose a
biological model whereby long-term physical activity lowers postmenopausal
breast cancer risk and to highlight gaps in the epidemiologic literature. To address the second aim, we summarized epidemiologic literature on 10 proposed
biomarkers, namely, body mass index (BMI),
estrogens,
androgens,
sex hormone binding globulin,
leptin,
adiponectin, markers of
insulin resistance,
tumor necrosis factor-alpha,
interleukin-6, and
C-reactive protein, in relation to postmenopausal
breast cancer risk and physical activity, respectively. Associations were deemed "convincing," "probable," "possible," or "hypothesized" using set criteria. Our proposed
biological model illustrated the co-occurrence of
overweight/
obesity,
insulin resistance, and chronic
inflammation influencing
cancer risk through interrelated mechanisms. The most convincing epidemiologic evidence supported associations between postmenopausal
breast cancer risk and BMI,
estrogens, and
androgens, respectively. In relation to physical activity, associations were most convincing for BMI,
estrone,
insulin resistance, and
C-reactive protein. Only BMI and
estrone were convincingly (or probably) associated with both postmenopausal
breast cancer risk and physical activity. There is a need for prospective cohort studies relating the proposed
biomarkers to
cancer risk and for long-term exercise randomized controlled trials comparing
biomarker changes over time, specifically in postmenopausal women. Future etiologic studies should consider interactions among
biomarkers, whereas exercise trials should explore exercise effects independently of
weight loss, different exercise prescriptions, and effects on central adiposity.