title: Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR).
abstract: BACKGROUND
  Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer.
  
  
  METHODS
  Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively.
  
  
  CONCLUSIONS
  This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier NCT01589367.
authors.forename: Jisun
authors.initials: J
authors.lastname: Kim
authors.forename: Woosung
authors.initials: W
authors.lastname: Lim
authors.forename: Eun-Kyu
authors.initials: EK
authors.lastname: Kim
authors.forename: Min-Kyoon
authors.initials: MK
authors.lastname: Kim
authors.forename: Nam-Sun
authors.initials: NS
authors.lastname: Paik
authors.forename: Sang-Seol
authors.initials: SS
authors.lastname: Jeong
authors.forename: Jung-Han
authors.initials: JH
authors.lastname: Yoon
authors.forename: Chan Heun
authors.initials: CH
authors.lastname: Park
authors.forename: Sei Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Lee Su
authors.initials: LS
authors.lastname: Kim
authors.forename: Sehwan
authors.initials: S
authors.lastname: Han
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Kang
authors.forename: Seung Il
authors.initials: SI
authors.lastname: Kim
authors.forename: Young Bum
authors.initials: YB
authors.lastname: Yoo
authors.forename: Joon
authors.initials: J
authors.lastname: Jeong
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Kim
authors.forename: Taewoo
authors.initials: T
authors.lastname: Kang
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Yongsik
authors.initials: Y
authors.lastname: Jung
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.forename: Ku Sang
authors.initials: KS
authors.lastname: Kim
authors.forename: Jong-Han
authors.initials: JH
authors.lastname: Yu
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Chae
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Jung
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Kang
authors.forename: Su Yun
authors.initials: SY
authors.lastname: Choi
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.affiliation: Department of Surgery, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul 110-744, Korea. hanw@snu.ac.kr.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D002985:Clinical Protocols; D005260:Female; D006801:Humans; D000077289:Letrozole; D008687:Metformin / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism*; D012107:Research Design; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D000077289:Letrozole; D008687:Metformin