The effect of metformin vs placebo on sex hormones in Canadian cancer trials group MA.32
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
- Vall d`Hebron Institute of Oncology (VHIO)
- Queen's University-Cancer Research Institute
- University of Western Ontario
- Applied Statistician
- Dana-Farber Cancer Institute
- Columbia University
- Vanderbilt-Ingram Cancer Center
- Mayo Clinic
- Hopital Enfant Jesus Site
- Baylor College of Medicine
- National Surgical Adjuvant Breast and Bowel Project
- BCCA-Vancouver Cancer Centre
- IBCSG Coordinating Centre
- BCCA-Cancer Centre for the Southern Interior
- Cancer Centre of Southeastern Ontario
- Health Sciences North
- London Regional Cancer Program
- University of Toronto
BACKGROUND: Metformin has been associated with lower breast cancer (BC) risk and improved outcomes in observational studies. Multiple biologic mechanisms have been proposed, including a recent report of altered sex hormones. We evaluated the effect of metformin on sex hormones in MA.32, a phase III trial of nondiabetic BC subjects who were randomly assigned to metformin or placebo.
METHODS: We studied the subgroup of postmenopausal hormone receptor-negative BC subjects not receiving endocrine treatment who provided fasting blood at baseline and at 6 months after being randomly assigned. Sex hormone-binding globulin, bioavailable testosterone, and estradiol levels were assayed using electrochemiluminescence immunoassay. Change from baseline to 6 months between study arms was compared using Wilcoxon sum rank tests and regression models.
RESULTS: 312 women were eligible (141 metformin vs 171 placebo); the majority of subjects in each arm had T1/2, N0, HER2-negative BC and had received (neo)adjuvant chemotherapy. Mean age was 58.1 (SD=6.9) vs 57.5 (SD=7.9) years, mean body mass index (BMI) was 27.3 (SD=5.5) vs 28.9 (SD=6.4) kg/m2 for metformin vs placebo, respectively. Median estradiol decreased between baseline and 6 months on metformin vs placebo (-5.7 vs 0 pmol/L; P < .001) in univariable analysis and after controlling for baseline BMI and BMI change (P < .001). There was no change in sex hormone-binding globulin or bioavailable testosterone.
CONCLUSION: Metformin lowered estradiol levels, independent of BMI. This observation suggests a new metformin effect that has potential relevance to estrogen sensitive cancers.
|Number of pages||7|
|Journal||Journal of the National Cancer Institute|
|Early online date||4 Jun 2020|
|Publication status||Published - Feb 2021|