Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Bernardo BonanniAndrea Decensi

Abstract

Metformin is associated with reduced breast cancer risk in observational studies in patients with diabetes, but clinical evidence for antitumor activity is unclear. The change in Ki-67 between pretreatment biopsy and post-treatment surgical specimen has prognostic value and may predict antitumor activity in breast cancer. After tumor biopsy, we randomly allocated 200 nondiabetic women with operable breast cancer to either metformin 850 mg/twice per day (n = 100) or placebo (n = 100). The primary outcome measure was the difference between arms in Ki-67 after 4 weeks adjusted for baseline values. Overall, the metformin effect on Ki-67 change relative to placebo was not statistically significant, with a mean proportional increase of 4.0% (95% CI, -5.6% to 14.4%) 4 weeks apart. However, there was a different drug effect depending on insulin resistance (homeostasis model assessment [HOMA] index > 2.8, fasting glucose [mmol/L] × insulin [mU/L]/22.5; P(interaction) = .045), with a nonsignificant mean proportional decrease in Ki-67 of 10.5% (95% CI, -26.1% to 8.4%) in women with HOMA more than 2.8 and a nonsignificant increase of 11.1% (95% CI, -0.6% to 24.2%) with HOMA less than or equal to 2.8. A different effect of metformin accordi...Continue Reading

References

Oct 17, 2001·The Journal of Clinical Investigation·G ZhouD E Moller
Feb 8, 2002·The New England Journal of Medicine·William C KnowlerUNKNOWN Diabetes Prevention Program Research Group
Jan 4, 2003·BMJ : British Medical Journal·G C JonesW D Alexander
Jun 5, 2003·Journal of the National Cancer Institute·Andrea DecensiUmberto Veronesi
Mar 16, 2006·Breast Cancer Research and Treatment·Lorraine L LipscombeJanet E Hux
Oct 26, 2006·Cancer Research·Mahvash ZakikhaniMichael Pollak
Jan 18, 2007·Journal of the National Cancer Institute·Mitch DowsettUNKNOWN IMPACT Trialists Group
Jan 4, 2008·The New England Journal of Medicine·John E Nestler
Feb 13, 2008·The American Journal of Clinical Nutrition·Michael N Pollack
Feb 19, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Pamela J Goodwin
Nov 5, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Giuseppe VialeUNKNOWN Breast International Group Trial 1-98
Jan 1, 2009·Journal of the National Cancer Institute·Marc J GunterHoward D Strickler
Feb 26, 2009·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Massimiliano CazzanigaAndrea Decensi
May 23, 2009·Science·Matthew G Vander HeidenCraig B Thompson
May 26, 2009·Breast Cancer Research : BCR·Marilyn L KwanBette J Caan
Jun 3, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Pamela J GoodwinVuk Stambolic
Jul 25, 2009·Nature Reviews. Cancer·David B Shackelford, Reuben J Shaw
Jul 31, 2009·The American Journal of Clinical Nutrition·Jill P CrandallUNKNOWN Diabetes Prevention Program Research Group
Aug 7, 2009·The New England Journal of Medicine·Eric L DingSimin Liu
Aug 25, 2009·Nature Reviews. Cancer·Elizabeth A Musgrove, Robert L Sutherland
Oct 24, 2009·Breast Cancer Research and Treatment·B MaitiH A Daw
Mar 6, 2010·Breast Cancer Research and Treatment·Kathryn N PhoenixKevin P Claffey
Mar 11, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ana M Gonzalez-Angulo, Funda Meric-Bernstam
Aug 19, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A DeCensiB Bonanni
Sep 3, 2010·Cancer Prevention Research·Regan M MemmottPhillip A Dennis
Oct 16, 2010·Cancer Prevention Research·Andrea DecensiSara Gandini
Dec 1, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrea DeCensi, Alessandra Gennari
Dec 2, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Jaclyn Lee Fong BoscoTimothy L Lash
Dec 28, 2010·Nature Genetics·UNKNOWN GoDARTS and UKPDS Diabetes Pharmacogenetics Study GroupEwan R Pearson
Jan 19, 2011·Clinical Pharmacokinetics·Garry G GrahamKenneth M Williams
Mar 18, 2011·International Journal of Cancer. Journal International Du Cancer·Sabina SieriVittorio Krogh
Jun 29, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A GoldhirschUNKNOWN Panel members
Oct 1, 2011·Journal of the National Cancer Institute·Mitch DowsettUNKNOWN International Ki-67 in Breast Cancer Working Group
Nov 3, 2011·JAMA : the Journal of the American Medical Association·Wendy Y ChenWalter C Willett

❮ Previous
Next ❯

Citations

Jun 25, 2013·Molecules and Cells·Yeon Kyung Choi, Keun-Gyu Park
Aug 1, 2012·Breast Cancer Research and Treatment·Nananda F ColRowan T Chlebowski
Aug 31, 2012·Breast Cancer Research and Treatment·Saroj NiraulaPamela J Goodwin
Nov 14, 2013·Journal of Mammary Gland Biology and Neoplasia·Rishi JainJoseph A Sparano
Mar 19, 2013·European Journal of Pharmacology·Christos V Rizos, Moses S Elisaf
Oct 2, 2013·Nature Reviews. Clinical Oncology·Naomi Gronich, Gad Rennert
Sep 4, 2013·The Journal of Clinical Investigation·Michael Pollak
Nov 19, 2013·Journal of Comparative Effectiveness Research·Kevin Kalinsky, Dawn L Hershman
Dec 20, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S GandiniA DeCensi
Jul 16, 2013·Oncogene·C A Cremona, A Behrens
May 4, 2013·Biochimica Et Biophysica Acta·Mahasin A OsmanEnrique Rodriguez-Boulan
May 16, 2014·Current Breast Cancer Reports·Beate C Litzenburger, Powel H Brown
May 28, 2014·Prostate Cancer and Prostatic Diseases·A M JoshuaM Pollak
Aug 28, 2014·Familial Cancer·Nabiha BashirMahmood Akhtar Kayani
Jul 12, 2014·Human Reproduction Update·Vanitha N SivalingamEmma J Crosbie
Sep 12, 2015·Expert Opinion on Drug Safety·Nicoletta ProvincialiAndrea DeCensi
Nov 12, 2014·Annual Review of Medicine·Daniel R Morales, Andrew D Morris
Nov 12, 2014·Annual Review of Medicine·Dimitrios Zardavas, Martine Piccart
Jan 23, 2016·British Journal of Cancer·V N SivalingamE J Crosbie
Feb 2, 2016·Cancer Treatment Reviews·Sandra SchmitzJean-Pascal Machiels
Aug 7, 2013·Hematology/oncology Clinics of North America·Matteo Lazzeroni, Andrea DeCensi
Mar 13, 2016·Seminars in Oncology·Brandy M Heckman-StoddardEva Szabo
Jan 2, 2013·Trends in Pharmacological Sciences·Arian Emami RiedmaierMatthias Schwab
Oct 18, 2013·Cancer Medicine·Heath D SkinnerPrajnan Das
May 21, 2014·Journal of Diabetes Investigation·Shi SenKeizo Kanasaki
Aug 19, 2015·CA: a Cancer Journal for Clinicians·Karen Colbert MaressoErnest T Hawk
Sep 16, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M MarousC Le Tourneau
Sep 26, 2015·Current Pharmacology Reports·Michael E GrossmannMargot P Cleary
Apr 14, 2015·BioMed Research International·Diana Hatoum, Eileen M McGowan
May 10, 2015·Cancer Causes & Control : CCC·Gregory S CalipDenise M Boudreau
Jun 27, 2015·Breast Cancer Research : BCR·Laura CamachoSao Jiralerspong
Jun 13, 2015·Journal of the National Cancer Institute. Monographs·Simon R LordAdrian L Harris
Mar 31, 2015·Cancer Treatment Reviews·Laura PizzutiMaddalena Barba

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.