TY - JOUR
T1 - The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32
AU - Pimentel, Isabel
AU - Chen, Bingshu E.
AU - Lohmann, Ana Elisa
AU - Ennis, Marguerite
AU - Ligibel, Jennifer
AU - Shepherd, Lois
AU - Hershman, Dawn L.
AU - Whelan, Timothy
AU - Stambolic, Vuk
AU - Mayer, Ingrid
AU - Hobday, Timothy
AU - Lemieux, Julie
AU - Thompson, Alastair
AU - Rastogi, Priya
AU - Gelmon, Karen
AU - Rea, Daniel
AU - Rabaglio, Manuela
AU - Ellard, Susan
AU - Mates, Mihaela
AU - Bedard, Philippe
AU - Pitre, Lacey
AU - Vandenberg, Theodore
AU - Dowling, Ryan J.O.
AU - Parulekar, Wendy
AU - Goodwin, Pamela J.
N1 - Funding Information:
This work was supported by the Canadian Cancer Society Research Institute, National Cancer Institute (US), Breast Cancer Research Foundation (New York), Canadian Breast Cancer Foundation, Hold'Em for Life, and Apotex Canada (in kind donation of placebo and metformin).
Publisher Copyright:
© 2020 The Author(s).
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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.
AB - 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.
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U2 - 10.1093/jnci/djaa082
DO - 10.1093/jnci/djaa082
M3 - Article
C2 - 33527137
AN - SCOPUS:85101002501
SN - 0027-8874
VL - 113
SP - 192
EP - 198
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 2
ER -