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Tytuł:
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The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32.
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Autorzy:
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Pimentel I; Vall d`Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Chen BE; Canadian Cancer Trials Group, Queen's University-Cancer Research Institute, Kingston, ON, Canada.
Lohmann AE; University of Western Ontario, London, ON, Canada.
Ennis M; Applied Statistician, Markham, ON, Canada.
Ligibel J; Dana-Farber Cancer Institute, Boston, MA, USA.
Shepherd L; Canadian Cancer Trials Group, Queen's University-Cancer Research Institute, Kingston, ON, Canada.
Hershman DL; Herbert Irving Cancer Center, Columbia University, New York, NY, USA.
Whelan T; Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON, Canada.
Stambolic V; University Health Network, Princess Margaret Hospital, Toronto, ON, Canada.
Mayer I; Vanderbilt University, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Hobday T; Mayo Clinic, Rochester, MN, USA.
Lemieux J; CHA-Hopital Du St-Sacrement, Hopital Enfant Jesus Site, Quebec City, Canada.
Thompson A; Baylor College of Medicine, Houston, TX, USA.
Rastogi P; National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA.
Gelmon K; BCCA-Vancouver Cancer Centre, Vancouver, BC, Canada.
Rea D; Institute of Cancer Research, Clinical Trials and Statistics Unit, Sutton, UK.
Rabaglio M; IBCSG Coordinating Centre, Bern, Switzerland.
Ellard S; BCCA-Cancer Centre for the Southern Interior, Kelowna, BC, Canada.
Mates M; Cancer Centre of Southeastern Ontario, Kingston, ON, Canada.
Bedard P; University Health Network, Princess Margaret Hospital, Toronto, ON, Canada.
Pitre L; Health Sciences North, Sudbury, ON, Canada.
Vandenberg T; London Regional Cancer Program, London, ON, Canada.
Dowling RJO; University Health Network, Princess Margaret Hospital, Toronto, ON, Canada.
Parulekar W; Canadian Cancer Trials Group , Queen's University-Cancer Research Institute, Kingston, ON, Canada.
Goodwin PJ; Lunenfeld Tanenbaum Research Institute at Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
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Źródło:
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Journal of the National Cancer Institute [J Natl Cancer Inst] 2021 Feb 01; Vol. 113 (2), pp. 192-198.
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Typ publikacji:
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Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: <2003-> : Cary, NC : Oxford University Press
Original Publication: Bethesda, Md., U. S. Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health; Washington, for sale by the Supt. of Docs., U. S. Govt. Print. Off.
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MeSH Terms:
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Breast Neoplasms/*drug therapy
Gonadal Steroid Hormones/*antagonists & inhibitors
Metformin/*administration & dosage
Body Mass Index ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Estradiol/genetics ; Female ; Gonadal Steroid Hormones/genetics ; Humans ; Middle Aged ; Receptor, ErbB-2/genetics ; Testosterone/antagonists & inhibitors ; Testosterone/genetics
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References:
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Br J Cancer. 2004 Jan 12;90(1):153-9. (PMID: 14710223)
J Natl Cancer Inst. 2018 Nov 1;110(11):1239-1247. (PMID: 29788487)
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Clin Breast Cancer. 2013 Dec;13(6):433-8. (PMID: 24267731)
J Natl Cancer Inst. 2018 Nov 1;110(11):1161-1162. (PMID: 29788134)
J Clin Endocrinol Metab. 2017 Dec 1;102(12):4588-4595. (PMID: 29029113)
Clin Breast Cancer. 2012 Jun;12(3):175-82. (PMID: 22607767)
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Nat Genet. 2011 Feb;43(2):117-20. (PMID: 21186350)
J Clin Endocrinol Metab. 2012 Aug;97(8):2853-61. (PMID: 22689695)
Breast Cancer Res Treat. 2010 Sep;123(2):591-6. (PMID: 20300828)
Cancer Res. 2007 Nov 15;67(22):10804-12. (PMID: 18006825)
Breast Cancer Res. 2015 Mar 03;17:32. (PMID: 25849721)
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Grant Information:
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P50 CA098131 United States CA NCI NIH HHS; U10 CA180863 United States CA NCI NIH HHS; U10 CA180888 United States CA NCI NIH HHS
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Substance Nomenclature:
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0 (Gonadal Steroid Hormones)
3XMK78S47O (Testosterone)
4TI98Z838E (Estradiol)
9100L32L2N (Metformin)
EC 2.7.10.1 (ERBB2 protein, human)
EC 2.7.10.1 (Receptor, ErbB-2)
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Entry Date(s):
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Date Created: 20210202 Date Completed: 20210618 Latest Revision: 20230919
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Update Code:
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20240104
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PubMed Central ID:
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PMC7850529
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DOI:
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10.1093/jnci/djaa082
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PMID:
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33527137
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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.
(© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
