The impact of diabetes and obesity on endometrial cancer outcomes.

Abstract

5523 Background: Diabetes (DM) is a known risk factor for endometrial cancer (EC), yet its effect on cancer outcomes remains unclear. We sought to investigate of the relationship between DM, obesity, and anti-diabetic medication on EC recurrence and survival. Methods: An IRB approved multi-institution retrospective study included all EC patients diagnosed with carcinosarcoma as well as endometrioid, serous, and clear cell cancers between January 2005 to December 2010. Demographics, comorbidities, and medications were captured at the time of cancer diagnosis. Cohorts for comparison included women with and without DM; and diabetics treated with metformin-only (METFO) were compared to those not treated with METFO. Cox regression models were used to evaluate the effect of selected covariates on PFS and OS. Results: Of 1495 EC patients, 364 (24%) had DM. Diabetics were more likely to be African American (30 v 16%, p<0.0001) and have higher BMIs (median 37.0 v 31.2, p < 0.001). After adjusting for age, race, stage, and BMI, women with DM had a worse OS (HR 1.40, 95CI 1.03-1.79), but similar recurrence risk (HR 1.16, 95CI 0.91-1.48) to non-diabetics. In a subset analysis of women with endometrioid EC (n = 1144), those with DM were 1.6 times more likely to recur (95CI 1.01-1.89, p = 0.04) and 2.4 times more likely to die (95CI 1.6-3.46, p < 0.0001). METFO use was associated with a decreased risk of recurrence (PFS HR 0.54, 95CI 0.3-0.96, p = 0.04), and death (OS HR 0.43, 95CI 0.22-0.83, p = 0.01) compared to no METFO use. METFO users had a similar clinical outcome compared to non-diabetics (PFS HR 1.05, p = 0.82; OS HR 1.3, p = 0.46). Obese women with DM who were treated with non-METFO regimens had a 1.8-fold increased risk of recurrence (95CI 0.94-3.7, p = 0.07) and 2.7-fold increased risk of death (95CI 1.2-5.9, p = 0.01). No survival differences were seen in women with serous, clear cell, or carcinosarcoma. Conclusions: Our data demonstrates worse clinical outcomes for EC patients with DM and improved outcomes for METFO users, suggesting a link between tumor pathogenesis and insulin growth factor and mTOR pathways. Future investigation is required to elucidate the complex relationship between diabetes, anti-hyperglycemic agents, and cancer outcomes.