In prior WHI reports, both higher physical activity levels  and fewer cardiometabolic risk factors  were associated with lower all-cause mortality following a breast cancer diagnosis in postmenopausal women. While in the current analyses, with longer follow-up, higher physical activity levels continued to be significantly associated with lower all-cause mortality following a breast cancer diagnosis, no significant interaction was seen between physical activity, number of cardiometabolic risk factors and breast cancer mortality. Thus, our study hypothesis was not supported.
To our knowledge, no study has examined the relationship between physical activity, cardiometabolic risk factors, and mortality among women with breast cancer. Current study findings support the established inverse association between physical activity and all-cause mortality among breast cancer survivors  as current study participants with breast cancer with higher physical activity levels had lower all-cause mortality. However, current study findings did not demonstrate that cardiometabolic risk factors modified this association.
In contrast, cardiometabolic risk factors modified the effect of a dietary intervention on breast cancer outcomes, as evaluated in the WHI randomized Dietary Modification (DM) trial. In the WHI DM trial, all 48,835 participants were free of prior breast cancer at entry and were randomly assigned to a low-fat dietary-pattern (40%) or a usual diet comparison group (60%). Changes associated with the dietary intervention included reduced fat intake; increased fruit, vegetable, and grain consumption, and weight reduction . While the trial was ongoing, the dietary intervention was also shown to reduce metabolic syndrome components when determined 3 years after entry . After long term, 19.6-year (median) follow-up, compared to women in the comparison group, women in the low-fat dietary intervention group had a statistically significant 21% reduction in death from breast cancer measured from study entry (132 [0.037% annualized risk] v 251 [0.047%] deaths, respectively; HR 0.79 95% CI 0.64–0.97, P = 0.02) . In a secondary analysis, women with 3–4 cardiometabolic risk factors, compared to women with no cardiometabolic risk factors, had a significantly higher risk of death from breast cancer, however, those with 3–4 cardiometabolic risk factors randomized to the dietary intervention had a statistically significant 69% reduction in this risk (HR 0.31 95% CI 0.14–0.69, interaction P = 0.01, compared to women with 0 or 1–2 risk factors) . Thus, in a randomized clinical trial setting, women having more metabolic syndrome components were more likely to benefit, in terms of reduction in breast cancer mortality, from a lifestyle intervention, randomization to a low-fat dietary pattern.
There is a study which could assess relationships among physical activity, cardiometabolic risk factors, and breast cancer outcome. The ongoing Women’s Health Initiative Strong and Healthy (WHISH) pragmatic physical activity intervention trial has completed randomization of 49,331 postmenopausal women testing whether a physical activity intervention reduces major cardiovascular events and all-cause mortality . A secondary analysis of associations among physical activity, metabolic syndrome components and breast cancer mortality would be well-powered to provide definitive assessment.
Current study strengths include the large sample size, prospective study design, use of a previously developed physical activity assessment tool, long follow-up and centralized, adjudicated breast cancer incidence and mortality outcomes. The study has limitations. First, the observational design precludes causal inferences. Second, reliance on questionnaire data for diabetes and cholesterol and reliance on baseline cardiometabolic risk factors and recreational physical activity assessment are limitations as well. Regarding the interval between cardiometabolic risk factor assessment, in a prior analysis in a WHI subgroup, metabolic syndrome status measured earlier in time (more years prior to breast cancer diagnosis) was more predictive of breast cancer risk compared to determinations made closer to breast cancer diagnosis [17, 18].