The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32. (4th June 2020)
- Record Type:
- Journal Article
- Title:
- The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32. (4th June 2020)
- Main Title:
- The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32
- 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 J O
Parulekar, Wendy
Goodwin, Pamela J - 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/m 2 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: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/m 2 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. … (more)
- Is Part Of:
- Journal of the National Cancer Institute. Volume 113:Number 2(2021)
- Journal:
- Journal of the National Cancer Institute
- Issue:
- Volume 113:Number 2(2021)
- Issue Display:
- Volume 113, Issue 2 (2021)
- Year:
- 2021
- Volume:
- 113
- Issue:
- 2
- Issue Sort Value:
- 2021-0113-0002-0000
- Page Start:
- 192
- Page End:
- 198
- Publication Date:
- 2020-06-04
- Subjects:
- Cancer -- Periodicals
Cancer -- Research -- Periodicals
616.994 - Journal URLs:
- https://jnci.oxfordjournals.org/ ↗
http://ukcatalogue.oup.com/ ↗ - DOI:
- 10.1093/jnci/djaa082 ↗
- Languages:
- English
- ISSNs:
- 0027-8874
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - 4830.000000
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- 26855.xml