title: Is it time to test metformin in breast cancer clinical trials?
abstract: 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.
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy. massimiliano.cazzaniga@ieo.it
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cazzaniga
authors.forename: Bernardo
authors.initials: B
authors.lastname: Bonanni
authors.forename: Aliana
authors.initials: A
authors.lastname: Guerrieri-Gonzaga
authors.forename: Andrea
authors.initials: A
authors.lastname: Decensi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000139:chemically induced*; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude
chemical_list: D014408:Biomarkers, Tumor; D007004:Hypoglycemic Agents; D008687:Metformin