Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

BMC Cancer

Jisun Kim¹⁴  Woosung Lim¹  Eun-Kyu Kim¹²  Min-Kyoon Kim¹³  Nam-Sun Paik¹  Sang-Seol Jeong¹¹  Jung-han Yoon³  Chan Heun Park¹⁷  Sei Hyun Ahn¹⁴  Lee Su Kim¹⁶  Sehwan Han¹⁰  Seok Jin Nam²  Han-Sung Kang¹⁸  Seung Il Kim⁴  Young Bum Yoo¹⁹  Joon Jeong¹⁵  Tae Hyun Kim⁷  Taewoo Kang⁸  Sung-Won Kim⁶  Yongsik Jung⁵  Jeong Eon Lee²  Ku Sang Kim⁵  Jong-Han Yu¹⁴  Byung Joo Chae¹¹  So-Youn Jung¹⁸  Eunyoung Kang⁶  Su Yun Choi⁹  Hyeong-Gon Moon¹³  Dong-Young Noh¹³  Wonshik Han¹³ 

[1] Department of Surgery, Ewha Womans University School of Medicine, Seoul, Korea

[2] Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

[3] Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea

[4] Department of Surgery, Yonsei University College of Medicine, Seoul, Korea

[5] Department of Surgery, Ajou University School of Medicine, Suwon, Korea

[6] Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea

[7] Department of Surgery, Inje University, Busan Paik Hospital, Busan, Korea

[8] Busan Cancer Center, Department of Surgery, College of Medicine, Pusan National University, Busan, Korea

[9] Division of Breast and Endocrine Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea

[10] Department of Surgery, Inje University Sanggye Paik Hospital, Seoul, Korea

[11] Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea

[12] Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Korea

[13] Department of Surgery, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul 110-744, Korea

[14] Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

[15] Breast Cancer Center, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

[16] Division of Breast and Endocrine Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea

[17] Department of Surgery, Breast and Thyroid Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

[18] Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea

[19] Department of Surgery, College of Medicine, Konkuk University, Seoul, Korea

关键词: Estrogen receptor-positive Breast cancer;    Neoadjuvant;    Letrozole;    Metformin;   

Others  :  858986
DOI  :  10.1186/1471-2407-14-170

 received in 2012-11-16, accepted in 2014-03-03,  发布年份 2014

【 摘 要 】

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/Design

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.

Discussion

This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer.

Trial registration

ClinicalTrials.gov Identifier NCT01589367

【 授权许可】

   
2014 Kim et al.; licensee BioMed Central Ltd.

【 图 表 】

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