Background: Based on the biological mechanisms underlying the obesity-breast cancer connections, potential protein biomarkers involved in breast cancer development have been identified, which may be helpful for the estimation of breast cancer risk. This study aimed to carry out a comprehensive overview of systematic reviews on circulating levels of obesity-related protein biomarkers for female breast cancer risk to provide a solid reference for potential breast cancer predictors.
Methods: Comprehensive literature searches were conducted in MEDLINE, EMBASE and Cochrane Database of Systematic Reviews up to Dec 2019. The AMSTAR tool was used for the methodological quality assessment of the included systematic reviews. Evidence was reported narratively.
Results: A total of 28 relevant systematic reviews which were mostly of moderate quality were included in the overview. Protein biomarkers relating to adipokines, insulin/insulin-like growth factor-1 (IGF-1) axis, inflammatory cytokines and sex hormones were investigated. Higher levels of circulating IGF-1, IGF-binding protein-3, leptin and resistin were found to be associated with an increased risk of premenopausal breast cancer; lower levels of circulating adiponectin and higher levels of circulating c-reactive protein, leptin, and resistin were found to be associated with an increased risk of postmenopausal breast cancer.
Conclusions: We found sufficient evidence on the positive associations between certain obesity-related protein biomarkers with pre- and/or postmenopausal breast cancer risk. These biomarkers could be used jointly as predictors, so as to build a comprehensive risk predictive score for female breast cancer.
Prospero registration number: CRD42020175328.
Keywords: Biomarker; Breast cancer; Obesity; Overview of systematic reviews; Proteins.