Is it Time to Test Metformin in Breast Cancer Clinical Trials?

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2009-03, Vol.18 (3), p.701-705
• Main Authors: CAZZANIGA, Massimiliano, BONANNI, Bernardo, GUERRIERI-GONZAGA, Aliana, DECENSI, Andrea
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biomarkers, Tumor - analysis; breast cancer and clinical trials; Breast Neoplasms - chemically induced; Clinical Trials as Topic; Diabetes Mellitus, Type 2 - drug therapy; Gynecology. Andrology. Obstetrics; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Mammary gland diseases; Medical sciences; metformin; Metformin - adverse effects; Metformin - therapeutic use; Mice; Mice, Nude; Tumors
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-08-0871

Several studies have identified an increased risk of cancer in type 2 diabetic patients and this is in accordance with the hypothesis that increased insulin levels might promote cancer. Thus, there is a great interest in exploring the possibility that antidiabetic therapies lowering insulin levels could decrease cancer incidence or cancer-related mortality. Recent observational studies have shown that metformin, an oral safe and well-tolerated insulin-sensitizer antidiabetic drug, has been associated with reduced cancer risk. Recently, several preclinical studies have evaluated the effect of metformin in vivo on nude mice and showed a significant reduction of both breast epithelial cell proliferation and protein synthesis. Further investigations in the clinical setting are well-supported by the promising results obtained thus far. At the European Institute of Oncology, the Division of Cancer Prevention and Genetics is planning to conduct a clinical trial to evaluate the activity of metformin on tumor cell proliferation in breast cancer patients undergoing surgery. It will be a presurgical randomized, double blind, placebo-controlled phase II biomarker trial: 100 histologically confirmed breast cancer patients will be randomly assigned to metformin (850 mg twice/daily) or placebo for 28 + 7 days till surgery to assess drug activity on tumor proliferation, as measured by Ki-67. The confirmation of the efficacy of metformin on cancer cell proliferation may lead the way to larger chemoprevention clinical trials. (Cancer Epidemiol Biomarkers Prev 2009;18(3):701–5)