Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2–Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial

Author:

Sonnenblick Amir1,Agbor-Tarh Dominique1,Bradbury Ian1,Di Cosimo Serena1,Azim Hatem A.1,Fumagalli Debora1,Sarp Severine1,Wolff Antonio C.1,Andersson Michael1,Kroep Judith1,Cufer Tanja1,Simon Sergio D.1,Salman Pamela1,Toi Masakazu1,Harris Lyndsay1,Gralow Julie1,Keane Maccon1,Moreno-Aspitia Alvaro1,Piccart-Gebhart Martine1,de Azambuja Evandro1

Affiliation:

1. Amir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of...

Abstract

Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this association in human epidermal growth factor receptor 2 (HER2 ) –positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination. In this substudy, we evaluated whether patients with diabetes at study entry—with or without metformin treatment—were associated with different disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) compared with patients without diabetes. Results A total of 8,381 patients were included in the current analysis: 7,935 patients (94.7%) had no history of diabetes at diagnosis, 186 patients (2.2%) had diabetes with no metformin treatment, and 260 patients (3.1%) were diabetic and had been treated with metformin. Median follow-up was 4.5 years (0.16 to 6.31 years), at which 1,205 (14.38%), 929 (11.08%), and 528 (6.3%) patients experienced DFS, DDFS, and OS events, respectively. Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio [HR], 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004). This effect was limited to hormone receptor–positive patients. Whereas insulin treatment was associated with a detrimental effect, metformin had a salutary effect in patients with diabetes who had HER2-positive and hormone receptor–positive breast cancer. Conclusion Metformin may improve the worse prognosis that is associated with diabetes and insulin treatment, mainly in patients with primary HER2-positive and hormone receptor–positive breast cancer.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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