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 - Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2021/2
Y1 - 2021/2
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.
UR - http://www.scopus.com/inward/record.url?scp=85101002501&partnerID=8YFLogxK
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 -
