Risk of Breast Cancer According to Glycaemia and HbA1c Concentration—A Meta-analysis of Prospective Studies

Some observational studies have suggested that women with diabetes may be at increased risk of breast cancer. Blood levels of fasting glucose (FG) and of glycated hemoglobin (HbA1c) are major diagnostic tools for diabetes. The aim of this study was to investigate the association between HbA1c, FG and breast cancer occurrence. A systematic literature search identified prospective studies which reported a quantitative estimate of the association between HbA1c or FG and breast cancer. Summary relative risks (SRR) of breast cancer, comparing high vs. low levels of HbA1c or FG, were computed using random-effect meta-analysis. Ten studies for HbA1c (116,035 women and 3,095 breast cancer cases) and 13 studies for FG (971,071 women and 14,579 breast cancer cases) were selected. High levels of HbA1c (FG) ranged from >4.5% to >9% (>5 to >7.8 mmol/L), and low level ranged from <4.3% to <6.7% (<4.4 to <6.1 mmol/L). Overall, the SRR of breast cancer was 0.97 (95% CI: 0.76, 1.24) for HbA1c and 1.15 (95% CI: 1.00, 1.33) for FG, with moderate heterogeneity between studies (I²=44% and 45%, respectively). When the analyses were restricted to women with HbA1c <6.5% and FG <7mmol/L, the SRR was 0.97 (95% CI: 0.81, 1.15) for HbA1c (six studies) and 1.15 (95% CI: 1.01, 1.31) for FG (seven studies) without heterogeneity in both analyses (I²=0%). In 3 studies conducted in diabetic women, the SRR for the association between HbA1c levels and breast cancer was 0.95 (95% CI: 0.79, 1.15) with no heterogeneity (I²=0%). No study was found on FG among diabetic women only. No association was found between HbA1c and breast cancer occurrence, while fasting glucose might be associated with a slight increased risk. The lack of clear association suggests that the increased risk of breast cancer observed among diabetic women appears to be driven by factors other than the blood glucose concentration disorders.