Physical Activity and Breast Cancer Risk: Evidence, Mechanisms, and Clinical Implications Original paper

What was reviewed?

This narrative review, “The Role of Physical Activity in Breast Cancer Prevention,” synthesizes epidemiological and mechanistic research on how physical activity influences breast cancer risk, with a particular focus on postmenopausal women. Drawing on cohort, case-control, and meta-analytic studies, the review evaluates the magnitude of risk reduction associated with various intensities and types of physical activity. It also explores the biological mechanisms underlying these associations, including hormonal regulation, inflammation, immune function, and metabolic changes. Notably, while the review does not directly assess microbiome composition, it highlights the multifactorial nature of breast cancer risk and the growing importance of modifiable lifestyle factors—such as exercise—that may intersect with microbiome-related pathways.

Who was reviewed?

The review encompasses evidence from multiple population subgroups, primarily focusing on women, since over 99% of breast cancer cases occur in females. It surveys data from premenopausal and postmenopausal women, including those with hereditary risk factors (e.g., BRCA1 and BRCA2 mutations) and those exposed to varying environmental and lifestyle risks. The review references studies with broad demographic representation, including cross-cultural research on breast cancer incidence in women who migrate from low- to high-risk countries, underscoring the significance of lifestyle and environmental exposures. While the review is not a systematic meta-analysis, it draws on systematic reviews, meta-analyses, and large-scale cohort studies to present a holistic view of the evidence.

Most important findings

A consistent body of evidence demonstrates a significant inverse association between physical activity, resistance training, and breast cancer risk. Systematic reviews and meta-analyses report risk reductions ranging from 10% to 80%, depending on the population, study design, and activity intensity. The average risk reduction is about 12–25%, with the strongest protective effect seen in postmenopausal women who engage in moderate-to-vigorous exercise sustained over the lifespan. The benefit is also evident for premenopausal women, particularly with vigorous activity. Importantly, the protective effect of physical activity appears independent of weight loss, indicating direct biological effects.

Mechanistically, physical activity is proposed to lower breast cancer risk through several pathways relevant to the emerging field of microbiome-host interaction. These include reductions in circulating estrogen, progesterone, and insulin-like growth factor-1 (IGF-1) levels, all of which are implicated in breast cancer pathogenesis. Exercise also leads to decreased levels of chronic inflammatory markers such as C-reactive protein (CRP) and enhances immune surveillance—specifically, increased natural killer cell activity, which is critical for the identification and destruction of abnormal cells. Notably, high-intensity interval training (HIIT) is linked to a more significant increase in natural killer cells compared to moderate exercise, suggesting a possible dose-response relationship.

Though not explicitly addressed in the review, these mechanisms may intersect with the gut microbiome, as both inflammation and estrogen metabolism are influenced by microbial communities. For example, the gut microbiota modulates systemic estrogen levels via β-glucuronidase expression and enterohepatic circulation, and physical activity is known to shape microbiome diversity and function. Therefore, the observed associations between exercise and breast cancer risk may, in part, be mediated by microbiome-driven metabolic and immunological pathways.

Key implications

The review strongly supports the promotion of physical activity as a viable, low-risk strategy to reduce breast cancer risk across diverse populations, especially among postmenopausal women. Public health recommendations should emphasize at least 150 minutes per week of moderate-intensity or 75 minutes of vigorous-intensity exercise, with additional benefits seen at higher activity levels. Clinicians should incorporate physical activity counseling into routine preventive care for women, regardless of baseline body weight or genetic risk. The potential for exercise to favorably modulate hormonal, inflammatory, and immune factors—possibly via microbiome interactions—underscores the need for further research into how these pathways converge. Integrating exercise into cancer prevention strategies may also complement emerging microbiome-targeted interventions, paving the way for more personalized, holistic approaches to breast cancer prevention.

Citation

Edwards D. The Role of Physical Activity in Breast Cancer Prevention. J Evol Health. 2019;4(1). doi:10.15310/J34146744