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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 J O; Parulekar, Wendy;

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

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  • Media type: E-Article
  • Title: The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32
  • Contributor: 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 J O; Parulekar, Wendy;
  • imprint: Oxford University Press (OUP), 2021
  • Published in: JNCI: Journal of the National Cancer Institute
  • Language: English
  • DOI: 10.1093/jnci/djaa082
  • ISSN: 0027-8874; 1460-2105
  • Keywords: Cancer Research ; Oncology
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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 &amp;lt; .001) in univariable analysis and after controlling for baseline BMI and BMI change (P &amp;lt; .001). There was no change in sex hormone-binding globulin or bioavailable testosterone.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Metformin lowered estradiol levels, independent of BMI. This observation suggests a new metformin effect that has potential relevance to estrogen sensitive cancers.</jats:p> </jats:sec>
  • Access State: Open Access