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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-A, 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.

Breast cancer is the most commonly diagnosed invasive malignancy and the second leading cause of cancer death in women. This chapter considers epidemiologic evidence regarding the association between physical activity and breast cancer risk from 73 studies conducted around the world. Across these studies there was a 25% average risk reduction amongst physically active women as compared to the least active women. The associations were strongest for recreational activity, for activity sustained over the lifetime or done after menopause, and for activity that is of moderate to vigorous intensity and performed regularly. There is also some evidence for a stronger effect of physical activity amongst postmenopausal women, women who are normal weight, have no family history of breast cancer, and are parous. It is likely that physical activity is associated with decreased breast cancer risk via multiple interrelated biologic pathways that may involve adiposity, sex hormones, insulin resistance, adipokines, and chronic inflammation. Future research should include prospective observational epidemiologic studies relating proposed biomarkers to breast cancer risk and also randomized controlled trials to examine how physical activity influences the proposed biomarkers. Exercise trials will provide more clarity regarding the appropriate type, dose, and timing of activity that relate to breast cancer risk reduction.

Activity energy expenditure (AEE) is the modifiable component of total energy expenditure (TEE) derived from all activities, both volitional and nonvolitional. Because AEE may affect health, there is interest in its estimation in free-living people. Physical activity questionnaires (PAQs) could be a feasible approach to AEE estimation in large populations, but it is unclear whether or not any PAQ is valid for this purpose. Our aim was to explore the validity of existing PAQs for estimating usual AEE in adults, using doubly labeled water (DLW) as a criterion measure. We reviewed 20 publications that described PAQ-to-DLW comparisons, summarized study design factors, and appraised criterion validity using mean differences (AEE(PAQ) - AEE(DLW), or TEE(PAQ) - TEE(DLW)), 95% limits of agreement, and correlation coefficients (AEE(PAQ) versus AEE(DLW) or TEE(PAQ) versus TEE(DLW)). Only 2 of 23 PAQs assessed most types of activity over the past year and indicated acceptable criterion validity, with mean differences (TEE(PAQ) - TEE(DLW)) of 10% and 2% and correlation coefficients of 0.62 and 0.63, respectively. At the group level, neither overreporting nor underreporting was more prevalent across studies. We speculate that, aside from reporting error, discrepancies between PAQ and DLW estimates may be partly attributable to 1) PAQs not including key activities related to AEE, 2) PAQs and DLW ascertaining different time periods, or 3) inaccurate assignment of metabolic equivalents to self-reported activities. Small sample sizes, use of correlation coefficients, and limited information on individual validity were problematic. Future research should address these issues to clarify the true validity of PAQs for estimating AEE.