Linking Physical Activity to Breast Cancer: Text Mining Results and a Protocol for Systematically Reviewing Three...

Area of Science:

• Integrative biology and cancer epidemiology.
• Mechanistic pathways linking lifestyle factors to disease risk.

Background:

• Epidemiological studies suggest physical activity reduces breast cancer risk.
• The causal link and underlying biological mechanisms remain unclear.
• Understanding these pathways is crucial for improving causal inference.

Purpose of the Study:

• To systematically review mechanistic pathways linking physical activity to breast cancer.
• To examine three specific pathways: sex steroid hormones, insulin signaling, and inflammation.
• To synthesize evidence for biological plausibility and identify research priorities.

Main Methods:

• A two-stage systematic review approach.
• Stage 1: Text Mining for Mechanism Prioritisation (TeMMPo) to identify biological intermediates.
• Stage 2: Systematic review of studies on physical activity-intermediates and intermediates-breast cancer.
• Searches in Ovid MEDLINE, EMBASE, and SPORTDiscus databases.
• Inclusion of human intervention and prospective observational studies.
• Meta-analysis, risk of bias assessment (Cochrane, ROBINS-I/E), and strength of evidence (GRADE).

Main Results:

• Synthesis of mechanistic evidence connecting physical activity to breast cancer risk through proposed pathways.
• Identification of key biological intermediates involved in the physical activity-breast cancer relationship.
• Assessment of the strength and quality of evidence for each pathway.

Conclusions:

• Mechanistic evidence supports a link between physical activity and reduced breast cancer risk via hormonal, insulin, and inflammatory pathways.
• Findings can inform future research directions and the design of targeted physical activity interventions.
• Strengthened causal inference regarding physical activity's role in breast cancer prevention.