The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32 Academic Article uri icon

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abstract

  • Abstract 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.

authors

  • Pimentel, Isabel
  • Chen, Bingshu E
  • Lohmann, Ana Elisa
  • Ennis, Marguerite
  • Ligibel, Jennifer
  • Shepherd, Lois
  • Hershman, Dawn L
  • Whelan, Timothy
  • Stambolic, Vuk
  • Mayer, Ingrid
  • Hobday, Timothy
  • Lemieux, Julie
  • Thompson, Alastair
  • Rastogi, Priya
  • Gelmon, Karen
  • Rea, Daniel
  • Rabaglio, Manuela
  • Ellard, Susan
  • Mates, Mihaela
  • Bedard, Philippe
  • Pitre, Lacey
  • Vandenberg, Theodore
  • Dowling, Ryan JO
  • Parulekar, Wendy
  • Goodwin, Pamela J

publication date

  • February 1, 2021