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Metformin, linked to lower cancer risk in epidemiologic and preclinical work, was evaluated in MA.32. Between 2010 and 2013, 3,649 nondiabetic breast cancer patients were randomized to metformin 850 mg twice daily or placebo for 5 years, then new first-event invasive primary cancers were identified and compared using competing risks and adjusted likelihood ratio tests.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/clinical-trial-updates-effect-of-metformin-versus-placebo-on-new-primary-cancers-in-canadian-cancer-trials-group-ma32-a-secondary-analysis-of-a-phase-iii-randomized-double-blind-trial-in-early-breast-cancer/378506/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/clinical-trial-updates-effect-of-metformin-versus-placebo-on-new-primary-cancers-in-canadian-cancer-trials-group-ma32-a-secondary-analysis-of-a-phase-iii-randomized-double-blind-trial-in-early-breast-cancer/378506.png","ImageObject",300,407,{"name":92,"@type":93},"Fans","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does the MA.32 secondary analysis address?","Question",{"text":112,"@type":113},"It evaluates whether metformin versus placebo affects the risk of new invasive primary cancers in early breast cancer patients.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were participants assigned in the study?",{"text":117,"@type":113},"Between 2010 and 2013, 3,649 nondiabetic patients with high-risk T1-3 N0-3 M0 breast cancer were randomized to metformin 850 mg twice daily or placebo twice daily for 5 years.",{"name":119,"@type":110,"acceptedAnswer":120},"What was the main finding regarding new cancer risk?",{"text":121,"@type":113},"Metformin did not reduce the risk of developing new primary cancers in these nondiabetic patients; hazard ratios for new invasive cancers were not statistically significant.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},378506,1790542623,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},5909892330395,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Clinical Trial Updates  \nEffect of Metformin Versus Placebo on New Primary Cancersin Canadian Cancer Trials Group MA.32: A Secondary Analysis of a Phase III Randomized Double-Blind Trial in Early Breast Cancer  \nPamela J. Goodwin, MD1 ; Bingshu E. Chen, PhD2 ; Karen A. Gelmon, MD3 ; Timothy J. Whelan, MD4 ; Marguerite Ennis, PhD5  ; Julie Lemieux, MD6; Jennifer A. Ligibel, MD7 ; Dawn L. Hershman, MD8 ; Ingrid A. Mayer, MD9 ; Timothy J. Hobday, MD10 ;  \nJudith M. Bliss, MSc11 ; Priya Rastogi, MD12 ; Manuela Rabaglio-Poretti, MD13; Alastair M. Thompson, MD14; Daniel W. Rea, PhD15  ; Paul M. Stos, BSc (Hon)2; Lois E. Shepherd, MD2 ; Vuk Stambolic, PhD16,17; and Wendy R. Parulekar, MD2   \nDOI [https://doi.org/10.1200/JCO.23.00296](https://doi.org/10.1200/JCO.23.00296)  \nABSTRACT  \nClinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.  \nMetformin has been associated with lower cancer risk in epidemiologic and preclinical research. In the MA.32 randomized adjuvant breast cancer trial, metformin (v placebo) did not affect invasive disease-free or overall survival. Here, we report metformin effects on the risk of new cancer. Between 2010 and 2013, 3,649 patients with breast cancer younger than 75 years without diabetes with high-risk T1-3, N0-3 M0 breast cancer (any estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2) were randomly assigned to metformin 850 mg orally twice a day or placebo twice a day for 5 years. New primary invasive cancers (outside the ipsilateral breast) developing as a first event were identified. Time to events was described by the competing risks method; two-sided likelihood ratio tests adjusting for age, BMI, smoking, and alcohol intake were used to compare metformin versus placebo arms. A total of 184 patients developed new invasive cancers: 102 metformin and 82 placebo, hazard ratio (HR), 1 .25; 95% CI, 0 . 94 to 1 . 68; P 5 .13. These included 48 contralateral invasive breast cancers (27 metformin v 21 placebo), HR, 1.29; 95% CI, 0.72 to 2.27; P 5 .40 and 136 new nonbreast primary cancers (75 metformin v 61 placebo), HR, 1.24; 95% CI, 0.88 to 1.74; P 5 .21. Metformin did not reduce the risk of new cancer development in these nondiabetic patients with breast cancer.  \nACCOMPANYING CONTENT  \n Appendix  \n Protocol  \nAccepted July 20, 2023  \nPublished September 11, 2023  \nJ Clin Oncol 41:5356-5362 © 2023 by American Society of Clinical Oncology  \nView Online Article  \nCreative Commons Attribution Non-Commercial No Derivatives 4.0 License  \nINTRODUCTION  \nMetformin, a biguanide commonly used to treat type 2 diabetes, has been associated with lower overall cancer risk in epidemiologic studies conducted in patients with diabetes.1 ,2 Meta-analyses of these studies have inconsistently identified lower risk of some types of cancer when individuals receive metformin.3-14 It has been suggested that data from observational studies of metformin and cancer risk seem largely unreliable, studies using designs least likely to be affected by bias (notably selection and time-related biases) being most likely to yield results that did not support a causal effect of metformin on cancer risk.15-17 The Diabetes Prevention Program trial, which randomly assigned adults with prediabetes to metformin, a lifestyle-based weight loss intervention or placebo, reported no effect of metformin  \nversus placebo on cancer mortality at 21-year follow-up (hazard ratio [HR], 1 . 04; 95% CI, 0 .72 to 1 . 52; P 5 . 83) .18  \nCurrent understanding of metformin action includes systemic effects resulting from reduced insulin signaling through PI3K/RAS pathways a","cbCaie9jutnDEDnL","https://ap.wps.com/l/cbCaie9jutnDEDnL","pdf",721505,"English","# Abstract\n## Study design and endpoints\n## Results on new primary cancers\n## Background and rationale","[{\"question\":\"What question does the MA.32 secondary analysis address?\",\"answer\":\"It evaluates whether metformin versus placebo affects the risk of new invasive primary cancers in early breast cancer patients.\"},{\"question\":\"How were participants assigned in the study?\",\"answer\":\"Between 2010 and 2013, 3,649 nondiabetic patients with high-risk T1-3 N0-3 M0 breast cancer were randomized to metformin 850 mg twice daily or placebo twice daily for 5 years.\"},{\"question\":\"What was the main finding regarding new cancer risk?\",\"answer\":\"Metformin did not reduce the risk of developing new primary cancers in these nondiabetic patients; hazard ratios for new invasive cancers were not statistically significant.\"}]","Clinical Trial Updates - Effect of Metformin Versus Placebo on New Primary Cancersin Canadian Cancer Trials Group MA.32 - A Secondary Analysis of a Phase III Randomized Double-Blind Trial in Early Breast Cancer | PDF",1790230369,23]