Metformin is associated with improved survival in endometrial cancer

• Published in: Gynecologic oncology 2014-02, Vol.132 (2), p.438-442
• Main Authors: Ko, Emily M, Walter, Paige, Jackson, Amanda, Clark, Leslie, Franasiak, Jason, Bolac, Corey, Havrilesky, Laura J, Secord, Angeles Alvarez, Moore, Dominic T, Gehrig, Paola A, Bae-Jump, Victoria
• Format: Article
• Language: English
• Subjects: Aged; Cohort Studies; Diabetes; Diabetes Mellitus - drug therapy; Disease-Free Survival; Endometrial cancer; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - mortality; Endometrial Neoplasms - pathology; Female; Hematology, Oncology and Palliative Medicine; Humans; Hypoglycemic Agents - therapeutic use; Metformin; Metformin - therapeutic use; Middle Aged; Obesity; Obstetrics and Gynecology; Prognosis; Retrospective Studies; Survival Analysis; Treatment Outcome; United States - epidemiology
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2013.11.021

Abstract Objective Preclinical evidence suggests that metformin exhibits anti-tumorigenic effects in endometrial cancer. We sought to investigate the association of metformin on endometrial cancer outcomes. Methods A multi-institutional IRB-approved retrospective cohort analysis was conducted comparing endometrial cancer patients with diabetes mellitus who used metformin (based on medication review at the time of diagnosis) to those who did not use metformin from 2005 to 2010. Metformin use on treatment related outcomes (TTR: time to recurrence; RFS: recurrence free survival; OS: overall survival) were evaluated using univariate and multivariate modeling. Results 24% (363/1495) endometrial cancer patients were diabetic, of whom 54% used metformin. Metformin users were younger and heavier than non-users, though nearly all were postmenopausal and obese. 75% of both groups had endometrioid histology. Stage, grade, and adjuvant therapy distributions were similar. Metformin users had improved RFS and OS. Non-metformin users had 1.8 times worse RFS (95% CI: 1.1–2.9, p = 0.02) and 2.3 times worse OS (95% CI: 1.3–4.2, p = 0.005) after adjusting for age, stage, grade, histology and adjuvant treatment. Metformin use was not associated with TTR. Conclusion Metformin use was associated with improved RFS and OS but not TTR, most likely due to improving all-cause mortality. Its role in modifying cancer recurrence remains unclear. Prospective studies that capture metformin exposure prior to, during and post endometrial cancer treatment may help define the role of metformin upon cancer specific and overall health outcomes.