Metformin use and endometrial cancer survival

Abstract

Objective Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancer using metformin have been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). Methods We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. Results Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. Conclusion Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC.

Metformin: A candidate for the treatment of gynecological tumors based on drug repositioning

“…Two studies have demonstrated the efficacy of metformin for the treatment of endometrial cancer (43,62). In these studies, the RR of treatment with metformin was 0.49 (95% CI, 0.32-0.73; P= 0.001), with no difference in the results in meta-analysis and no heterogeneity (I 2 = 0%) (58).…”

Clinical benefits of metformin in gynecologic oncology

“…Obesity is a major risk factor for endometrial cancer; therefore, the incidence of endometrial cancer has been predicted to increase as a consequence of the obesity epidemic, which may also worsen endometrial cancer outcomes (42,43). However, the association between endometrial cancer and obesity varies according to disease histology.…”

“…Obesity exhibits a greater association with the risk of endometrioid (type 1) endometrial cancer, than non-endometrioid (type 2) endometrial cancer (44). Data from multiple studies has indicated that the obesity-endometrial cancer association occurs as a result of the higher average circulating insulin and estradiol levels detected in obese females, and that this effect is specific to endometrioid tumors (42,45,46). There are a number of clinical studies regarding the effect of metformin on endometrial cancer outcomes.…”

“…However, these results do not consider cancer pathology, stage or treatment strategy, which are significant factors, given the biological heterogeneity of endometrial cancer subtypes. Another retrospective study reported improved overall survival rates among diabetic patients on metformin with non-endometrioid type cancer, compared with that of non-metformin users and non-diabetic patients; however, cancer specific recurrence or progression were not reported (42). In a multi-institutional retrospective cohort analysis, the effects of metformin use on treatment-associated outcomes of endometrial cancer were evaluated using univariate and multivariate modeling (48).…”

“…Regarding non-endometrioid endometrial cancer, diabetic endometrial cancer patients with non-endometrioid tumors who were taking metformin were demonstrated to have a lower risk of mortality than that of patients with endometrial cancer who did not use metformin (42). Metformin may therefore function as an adjuvant therapy for the treatment of non-endometrioid endometrial cancer.…”