Breast Cancer and Subsequent Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Background: Breast cancer (BC) is the most common non-skin malignancy in women. Drugs used to treat BC may have adverse effects that lead to an increased risk of developing type 2 diabetes mellitus (T2D). Due to improvements in BC diagnostics, treatment and follow-up, the population of BC survivors is growing - making more women susceptible to these potentially adverse effects and T2D.

Objectives: We conducted a systematic review and meta-analysis to investigate the association between BC and subsequent incident T2D overall, and according to the receipt of BC treatments—endocrine therapy (ET) (tamoxifen and aromatase inhibitors (AIs)) and chemotherapy.

Methods: Through September 2021, PubMed, Embase and references of relevant papers were searched for studies on BC, BC treatment, and subsequent T2D risk. We initially screened papers by title and abstract and subsequently reviewed for eligibility and data extraction. Using random-effects models, we calculated summary relative risks (RRs) and associated 95% confidence intervals (CIs) of T2D for BC vs. no cancer; and according to BC treatments: ET vs. no ET, tamoxifen vs. no tamoxifen, AIs vs. no AIs, and chemotherapy vs. no chemotherapy. Both non-cancer referents and BC patients who did not use the treatment in question were used separately as referents in the analyses of ET, tamoxifen, and AIs. We used funnel plots to assess publication bias.

Results: Among 14 studies eligible for inclusion, 7 reported on the association between BC and T2D risk; 3 on chemotherapy and T2D; 8 on ET (6 on tamoxifen and 4 on AIs) and T2D; and 4 studies investigated more than one association. The pooled RR of incident T2D after BC vs. no cancer was 1.29 (95%CI=1.17-1.43). BC patients who received tamoxifen had higher risk of T2D compared with BC patients who did not receive tamoxifen (RR=1.23, 95%CI=1.10-1.37), and compared with a non-cancer referent group (RR=1.15, 95%CI=0.94-1.40). Due to too few studies, no pooled estimates were calculated for the effects of ET overall, AIs and chemotherapy.

Conclusions: Our findings support an association between BC and subsequently elevated risk of T2D, particularly after tamoxifen use. Further research is needed to determine the association of ET overall, AIs and chemotherapy on the incidence of T2D in BC patients.