Linking physical activity to breast cancer via inflammation, Part 2: The effect of inflammation on breast cancer risk.

This review synthesized and appraised the evidence for an effect of inflammation on breast cancer risk. Systematic searches identified prospective cohort and Mendelian randomization studies relevant to this review. Meta-analysis of 13 biomarkers of inflammation were conducted to appraise the evidence for an effect breast cancer risk; we examined the dose-response of these associations. Risk of bias was evaluated using the ROBINS-E tool and the quality of evidence was appraised with Grading of Recommendations Assessment, Development, and Evaluation. Thirty-four observational studies and three Mendelian randomization studies were included. Meta-analysis suggested that women with the highest levels of C-reactive protein had a higher risk of developing breast cancer (RR=1.13, 95% CI=1.01, 1.26) compared to women with the lowest levels. Women with highest levels of adipokines, particularly adiponectin (RR=0.76, 95% CI=0.61, 0.91) had a reduced breast cancer risk, although this finding was not supported by Mendelian randomization analysis. There was little evidence of an effect of cytokines, including TNF- and IL-6, on breast cancer risk. The quality of evidence for each biomarker ranged from very low to moderate. Beyond CRP, the published data do not clearly support the role of inflammation in the development of breast cancer.