Influence of Breast Cancer and Metastases on Incidence of Diabetes

Abstract Purpose: Diabetes increases the risk of subsequent breast cancer. However, the inverse relationship of breast cancer to incident diabetes development is unclear. In preclinical models increased bone turnover due to bone metastases or endocrine therapies impacts insulin secretion. This analysis was conducted to estimate the incidence of diabetes after breast cancer and the influence of metastases and therapeutic agents. Methods: This retrospective case-control study combined data from a large electronic health data exchange and the Indiana State Cancer Registry on breast cancer patients and controls between 2007 and 2017. Primary exposure was presence of breast cancer and bone or non-bone metastases. The primary outcome was frequency of incident diabetes detected by ICD codes, medication use, or laboratory results, compared between breast cancer cases and controls using conditional or ordinary logistic regressions. Results: 36,083 cases and 36,083 matched controls were detected. Incident diabetes was higher in early stage breast cancer (OR 1.17, 95%CI 1.11-1.23, p<0.0001) and metastatic breast cancer (OR 1.62, 95% CI 1.25-2.09, p=0.0002), compared to controls. Bone metastases conferred higher odds of both pre-existing (OR 1.20, 95% CI 1.03-1.63, p=0.0272) and incident diabetes (OR 1.64, 95% CI 1.19-2.25, p=0.0021). Endocrine therapy was associated with reduced diabetes (OR 0.86, 95% CI 0.79-0.83, p=0.002). Anti-resorptives reduced incident diabetes in those with bone metastases (OR 0.44, 95% CI 0.25-0.78, p=0.005). Conclusion: Breast cancer, especially with metastases, increases subsequent risk of diabetes. As patients with breast cancer live longer, identifying and managing diabetes may impact treatment delivery, cost, survival, and quality of life.