Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol

Persistent Link:
http://hdl.handle.net/10150/618734
Title:
Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol
Author:
Martinez, Jessica A.; Chalasani, Pavani; Thomson, Cynthia A.; Roe, Denise; Altbach, Maria; Galons, Jean-Philippe; Stopeck, Alison; Thompson, Patricia A.; Villa-Guillen, Diana Evelyn; Chow, H-H. Sherry
Affiliation:
Univ Arizona, Ctr Canc; Univ Arizona, Dept Nutr Sci; Univ Arizona, Dept Epidemiol & Biostat; Univ Arizona, Dept Med Imaging
Issue Date:
2016-07-19
Publisher:
BIOMED CENTRAL LTD
Citation:
Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol 2016, 16 (1) BMC Cancer
Journal:
BMC Cancer
Rights:
© 2016 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Collection Information:
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
Abstract:
Background: Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. Methods/design: This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n=75) or placebo (n=75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. Discussion: The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin in a growing population at risk for multiple diseases.
Note:
Open Access Journal
ISSN:
1471-2407
PubMed ID:
27430256
DOI:
10.1186/s12885-016-2551-3
Keywords:
Metformin; Breast cancer prevention; Breast density; Biomarkers; Metabolic syndrome; Metabolomics
Version:
Final published version
Sponsors:
National Cancer Institute [1R01CA172444-01A1]; [CCR14299136]
Additional Links:
http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2551-3

Full metadata record

DC FieldValue Language
dc.contributor.authorMartinez, Jessica A.en
dc.contributor.authorChalasani, Pavanien
dc.contributor.authorThomson, Cynthia A.en
dc.contributor.authorRoe, Deniseen
dc.contributor.authorAltbach, Mariaen
dc.contributor.authorGalons, Jean-Philippeen
dc.contributor.authorStopeck, Alisonen
dc.contributor.authorThompson, Patricia A.en
dc.contributor.authorVilla-Guillen, Diana Evelynen
dc.contributor.authorChow, H-H. Sherryen
dc.date.accessioned2016-08-24T01:21:05Z-
dc.date.available2016-08-24T01:21:05Z-
dc.date.issued2016-07-19-
dc.identifier.citationPhase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol 2016, 16 (1) BMC Canceren
dc.identifier.issn1471-2407-
dc.identifier.pmid27430256-
dc.identifier.doi10.1186/s12885-016-2551-3-
dc.identifier.urihttp://hdl.handle.net/10150/618734-
dc.description.abstractBackground: Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. Methods/design: This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n=75) or placebo (n=75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. Discussion: The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin in a growing population at risk for multiple diseases.en
dc.description.sponsorshipNational Cancer Institute [1R01CA172444-01A1]; [CCR14299136]en
dc.language.isoenen
dc.publisherBIOMED CENTRAL LTDen
dc.relation.urlhttp://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2551-3en
dc.rights© 2016 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).en
dc.subjectMetforminen
dc.subjectBreast cancer preventionen
dc.subjectBreast densityen
dc.subjectBiomarkersen
dc.subjectMetabolic syndromeen
dc.subjectMetabolomicsen
dc.titlePhase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocolen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Ctr Cancen
dc.contributor.departmentUniv Arizona, Dept Nutr Scien
dc.contributor.departmentUniv Arizona, Dept Epidemiol & Biostaten
dc.contributor.departmentUniv Arizona, Dept Med Imagingen
dc.identifier.journalBMC Canceren
dc.description.noteOpen Access Journalen
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen

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