Metformin intervention in obese non-diabetic patients with breast cancer: phase II randomized, double-blind, placebo-controlled trial

Breast Cancer Research and Treatment

Volumn 153, Issue 2, 2015, Pages 361-370

  Ko, Kwang Pil ^a   Ma, Seung Hyun ^b,c   Yang, Jae Jeong ^b   Hwang, Yunji ^b,c   Ahn, Choonghyun ^b,c   Cho, Young Min ^b   Noh, Dong Young ^b,c   Park, Byung Joo ^b   Han, Wonshik ^b,c   Park, Sue K ^b,c  

^a Gachon University   (South Korea)

^b Seoul National University College of Medicine   (South Korea)

^c Seoul National University   (South Korea)

Author keywords

Breast cancer; Glucose; Metformin; Postoperative adjuvant

Indexed keywords

GLUCOSE; HEMOGLOBIN A1C; METFORMIN; PLACEBO; TAMOXIFEN; ANTIDIABETIC AGENT; BIOLOGICAL MARKER;

ARTICLE; BODY MASS; BREAST CANCER; CANCER RECURRENCE; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; FEMALE; HUMAN; IMPAIRED GLUCOSE TOLERANCE; MAJOR CLINICAL STUDY; MASTECTOMY; OBESITY; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGNOSIS; RANDOMIZED CONTROLLED TRIAL; WEIGHT REDUCTION; BREAST NEOPLASMS; CANCER STAGING; CLINICAL TRIAL; COMPLICATION; METABOLISM; PATHOLOGY; TIME FACTOR; TREATMENT OUTCOME;

BIOMARKERS; BREAST NEOPLASMS; FEMALE; HUMANS; HYPOGLYCEMIC AGENTS; METFORMIN; NEOPLASM STAGING; OBESITY; TIME FACTORS; TREATMENT OUTCOME;

EID: 84940960836     PISSN: 01676806     EISSN: 15737217     Source Type: Journal    
DOI: 10.1007/s10549-015-3519-8     Document Type: Article

References (22)

1. Gonzalez-Angulo AM, Meric-Bernstam F (2010) Metformin: a therapeutic opportunity in breast cancer. Clin Cancer Res 16(6):1695–1700
2. Nakano M, Inui A (2012) Metformin and incretin-based therapies up-regulate central and peripheral adenosine monophosphate-activated protein affecting appetite and metabolism. Indian J Endocrinol Metab 16(Suppl 3):S529–531. doi:10.4103/2230-8210.105567
3. Hadad SM, Fleming S, Thompson AM (2008) Targeting AMPK: a new therapeutic opportunity in breast cancer. Crit Rev Oncol Hematol 67(1):1–7
4. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM, Diabetes Prevention Program Research Group (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346(6):393–403
5. Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, Lind SE, Thor AD (2009) Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle 8(6):909–915
6. Malki A, Youssef A (2011) Antidiabetic drug metformin induces apoptosis in human MCF breast cancer via targeting ERK signaling. Oncol Res 19(6):275–285
7. Bowker SL, Yasui Y, Veugelers P, Johnson JA (2010) Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure. Diabetologia 53(8):1631–1637
8. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330(7503):1304–1305
9. Monami M, Colombi C, Balzi D, Dicembrini I, Giannini S, Melani C, Vitale V, Romano D, Barchielli A, Marchionni N, Rotella CM, Mannucci E (2011) Metformin and cancer occurrence in insulin-treated type 2 diabetic patients. Diabetes Care 34(1):129–131
10. Currie CJ, Poole CD, Jenkins-Jones S, Gale EA, Johnson JA, Morgan CL (2012) Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care 35(2):299–304
11. Goodwin PJ, Pritchard KI, Ennis M, Clemons M, Graham M, Fantus IG (2008) Insulin-lowering effects of metformin in women with early breast cancer. Clin Breast Cancer 8(6):501–505. doi:10.3816/CBC.2008.n.060
12. Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN, Gonzalez-Angulo AM (2009) Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 27(20):3297–3302. doi:10.1200/JCO.2009.19.6410
13. Erickson K, Patterson RE, Flatt SW, Natarajan L, Parker BA, Heath DD, Laughlin GA, Saquib N, Rock CL, Pierce JP (2011) Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast cancer. J Clin Oncol 29(1):54–60. doi:10.1200/JCO.2010.29.3183
14. WHOIOTF/IASO (2000) The Asia-Pacific perspective: redefining obesity and its treatment. Int Diabetes Inst, Melbourne
15. Wu RR, Zhao JP, Jin H, Shao P, Fang MS, Guo XF, He YQ, Liu YJ, Chen JD, Li LH (2008) Lifestyle intervention and metformin for treatment of antipsychotic-induced weight gain: a randomized controlled trial. JAMA 299(2):185–193
16. Campagnoli C, Pasanisi P, Abba C, Ambroggio S, Biglia N, Brucato T, Colombero R, Danese S, Donadio M, Venturelli E, Zito G, Berrino F (2012) Effect of different doses of metformin on serum testosterone and insulin in non-diabetic women with breast cancer: a randomized study. Clin Breast Cancer 12(3):175–182. doi:10.1016/j.clbc.2012.03.004
17. Niraula S, Dowling RJ, Ennis M, Chang MC, Done SJ, Hood N, Escallon J, Leong WL, McCready DR, Reedijk M, Stambolic V, Goodwin PJ (2012) Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study. Breast Cancer Res Treat 135(3):821–830. doi:10.1007/s10549-012-2223-1
18. Bonanni B, Puntoni M, Cazzaniga M, Pruneri G, Serrano D, Guerrieri-Gonzaga A, Gennari A, Trabacca MS, Galimberti V, Veronesi P, Johansson H, Aristarco V, Bassi F, Luini A, Lazzeroni M, Varricchio C, Viale G, Bruzzi P, Decensi A (2012) Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial. J Clin Oncol 30(21):2593–2600. doi:10.1200/JCO.2011.39.3769
19. Hadad S, Iwamoto T, Jordan L, Purdie C, Bray S, Baker L, Jellema G, Deharo S, Hardie DG, Pusztai L, Moulder-Thompson S, Dewar JA, Thompson AM (2011) Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat 128(3):783–794. doi:10.1007/s10549-011-1612-1
20. Goodwin PJ, Parulekar WR, Gelmon KA, Shepherd LE, Ligibel JA, Hershman DL, Rastogi P, Mayer IA, Hobday TJ, Lemieux J, Thompson AM, Pritchard KI, Whelan TJ, Mukherjee SD, Chalchal HI, Oja CD, Tonkin KS, Bernstein V, Chen BE, Stambolic V (2015) Effect of metformin vs placebo on and metabolic factors in NCIC CTG MA.32. J Nat Cancer Inst 107(3). doi:10.1093/jnci/djv006
21. Zhuang Y, Miskimins WK (2008) Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1. J Mol Signal 3:18. doi:10.1186/1750-2187-3-18
22. Goodwin PJ, Stambolic V (2011) Obesity and insulin resistance in breast cancer–chemoprevention strategies with a focus on metformin. Breast 20(Suppl 3):S31–35. doi:10.1016/S0960-9776(11)70291-0