Emily M Ko1, Paige Walter2, Amanda Jackson3, Leslie Clark4, Jason Franasiak4, Corey Bolac2, Laura J Havrilesky5, Angeles Alvarez Secord5, Dominic T Moore6, Paola A Gehrig7, Victoria Bae-Jump8. 1. University of Pennsylvania, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, USA. 2. Department of Obstetrics and Gynecology, Duke University, USA. 3. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, USA. 4. Department of Obstetrics and Gynecologic Oncology, University of North Carolina at Chapel Hill, USA. 5. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University, USA. 6. University of North Carolina Lineberger Comprehensive Cancer Center, USA. 7. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, USA; University of North Carolina Lineberger Comprehensive Cancer Center, USA. 8. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, USA; University of North Carolina Lineberger Comprehensive Cancer Center, USA. Electronic address: vbae@unch.unc.edu.
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.
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 cancerpatients 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 cancerpatients 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.
Authors: Amanda de Barros Machado; Vania Dos Reis; Sebastian Weber; Julia Jauckus; Ilma Simoni Brum; Helena von Eye Corleta; Thomas Strowitzki; Edison Capp; Ariane Germeyer Journal: Oncol Lett Date: 2016-08-23 Impact factor: 2.967