TY - JOUR
T1 - Impact of diabetes, insulin, and metformin use on the outcome of patients with human epidermal growth factor receptor 2-positive primary breast cancer
T2 - Analysis from the ALTTO phase III randomized trial
AU - Sonnenblick, Amir
AU - Agbor-Tarh, Dominique
AU - Bradbury, Ian
AU - Di Cosimo, Serena
AU - Azim, Hatem A.
AU - Fumagalli, Debora
AU - Sarp, Severine
AU - Wolff, Antonio C.
AU - Andersson, Michael
AU - Kroep, Judith
AU - Cufer, Tanja
AU - Simon, Sergio D.
AU - Salman, Pamela
AU - Toi, Masakazu
AU - Harris, Lyndsay
AU - Gralow, Julie
AU - Keane, Maccon
AU - Moreno-Aspitia, Alvaro
AU - Piccart-Gebhart, Martine
AU - De Azambuja, Evandro
N1 - Publisher Copyright:
© 2017 by American Society of Clinical Oncology.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2016.69.7722
DO - 10.1200/JCO.2016.69.7722
M3 - Article
C2 - 28375706
AN - SCOPUS:85016977704
SN - 0732-183X
VL - 35
SP - 1421
EP - 1429
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 13
ER -