Long-term metformin use is associated with decreased risk of breast cancer

Michael Bodmer, Christian Meier, Stephan Krähenbühl, Susan S Jick, Christoph R Meier, Michael Bodmer, Christian Meier, Stephan Krähenbühl, Susan S Jick, Christoph R Meier

Abstract

Objective: To evaluate whether use of oral hypoglycemic agents is associated with an altered breast cancer risk in women.

Research design and methods: Using the U.K.-based General Practice Research Database, we conducted a nested case-control analysis among 22,621 female users of oral antidiabetes drugs with type 2 diabetes. We evaluated whether they had an altered risk of breast cancer in relation to use of various types of oral hypoglycemic agents. Case and control patients with a recorded diagnosis of type 2 diabetes were matched on age, calendar time, and general practice, and the multivariate conditional logistic regression analyses were further adjusted for use of oral antidiabetes drugs, insulin, estrogens, smoking BMI, diabetes duration, and HbA1c (A1C).

Results: We identified 305 case patients with a recorded incident diagnosis of breast cancer. The mean +/- SD age was 67.5 +/- 10.5 years at the time of the cancer diagnosis. Long-term use of >or=40 prescriptions (>5 years) of metformin, based on 17 exposed case patients and 120 exposed control patients, was associated with an adjusted odds ratio of 0.44 (95% CI 0.24-0.82) for developing breast cancer compared with no use of metformin. Neither short-term metformin use nor use of sulfonylureas or other antidiabetes drugs was associated with a materially altered risk for breast cancer.

Conclusions: A decreased risk of breast cancer was observed in female patients with type 2 diabetes using metformin on a long-term basis.

References

    1. Xue F, Michels KB: Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence. Am J Clin Nutr 2007;86:s823–s835
    1. Frasca F, Pandini G, Sciacca L, Pezzino V, Squatrito S, Belfiore A, Vigneri R: The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem 2008;114:23–37
    1. Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE: Increased prevalence of prior breast cancer in women with newly diagnosed diabetes. Breast Cancer Res Treat 2006;98:303–309
    1. Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, Hartwick W, Hoffman B, Hood N: Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 2002;20:42–51
    1. Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE: The impact of diabetes on survival following breast cancer. Breast Cancer Res Treat 2008;109:389–395
    1. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD: Metformin and reduced risk of cancer in diabetic patients. BMJ 2005;330:1304–1305
    1. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM: New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 2009;32:1620–1625
    1. Bowker SL, Majumdar SR, Veugelers P, Johnson JA: Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006;29:254–258
    1. Currie CJ, Poole CD, Gale EA: The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 2009;52:1766–1777
    1. Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN, Gonzalez-Angulo AM: Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 2009;27:3297–3302
    1. Landman GW, Kleefstra N, van Hateren KJ, Groenier KH, Gans RO, Bilo HJ: Metformin associated with lower cancer mortality in type 2 diabetes. ZODIAC-16. Diabetes Care 2010;33:322–326
    1. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Kovalenko IG, Poroshina TE, Semenchenko AV, Provinciali M, Re F, Franceschi C: Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Exp Gerontol 2005;40:685–693
    1. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M: Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res 2006;66:10269–10273
    1. Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N: Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res 2007;67:10804–10812
    1. Wood L, Martinez C: The general practice research database: role in pharmacovigilance. Drug Saf 2004;27:871–881
    1. Jick SS, Kaye JA, Vasilakis-Scaramozza C, Garcia Rodríguez LA, Ruigómez A, Meier CR, Schlienger RG, Black C, Jick H: Validity of the general practice research database. Pharmacotherapy 2003;23:686–689
    1. Bodmer M, Meier C, Krähenbühl S, Jick SS, Meier CR: Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis. Diabetes Care 2008;31:2086–2091
    1. Brauchli YB, Jick SS, Curtin F, Meier CR: Association between use of thiazolidinediones or other oral antidiabetics and psoriasis: A population based case-control study. J Am Acad Dermatol 2008;58:421–429
    1. Meier C, Kraenzlin ME, Bodmer M, Jick SS, Jick H, Meier CR: Use of thiazolidinediones and fracture risk. Arch Intern Med 2008;168:820–825
    1. Kaye JA, Derby LE, del Mar Melero-Montes M, Quinn M, Jick H: The incidence of breast cancer in the General Practice Research Database compared with national cancer registration data. Br J Cancer 2000;83:1556–1558
    1. Del Giudice ME, Fantus IG, Ezzat S, McKeown-Eyssen G, Page D, Goodwin PJ: Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat 1998;47:111–120
    1. Goodwin PJ: Insulin in the adjuvant breast cancer setting: a novel therapeutic target for lifestyle and pharmacologic interventions? J Clin Oncol 2008;26:833–834
    1. Pollack MN: Insulin, insulin-like growth factors, insulin resistance, and neoplasia. Am J Clin Nutr 2007;86:s820–822
    1. Govindarajan R, Ratnasinghe L, Simmons DL, Siegel ER, Midathada MV, Kim L, Kim PJ, Owens RJ, Lang NP: Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. J Clin Oncol 2007;25:1476–1481
    1. Cazzaniga M, Bonanni B, Guerrieri-Gonzaga A, Decensi A: Is it time to test metformin in breast cancer clinical trials? Cancer Epidemiol Biomarkers Prev 2009;18:701–705

Source: PubMed

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