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Metformin intervention against ovarian toxicity during chemotherapy for early breast cancer: Study protocol for a randomized double-blind placebo-controlled trial

  • Jinjin Zhang
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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  • Xiangyi Ma
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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  • Ya Li
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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  • Ronghua Liu
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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  • Yan Li
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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  • Panshi Zhang
    Affiliations
    Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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  • Wu Ren
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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  • Pengfei Cui
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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  • Bo Wang
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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  • Minli Zhang
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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  • Yan Jin
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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  • Xingrui Li
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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  • Shixuan Wang
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China
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      Highlights

      • This study can provide a potential alternative drug protecting female fertility for early breast cancer patients, which could be useful for clinical programs.
      • This study may provide a useful strategy that improves the life quality and long-term prognosis such as OS, ORR and DFS for early breast cancer patients.
      • This project can be of clinical and long-term strategic significance, which could alleviate economic pressure as the cancer patients are trending younger.

      Abstract

      Background

      With the significant improvement of the cure rate and survival rate of cancer patients, the survivors face quality-of-life problems, such as a significant decline in reproductive system development, ovarian reserves and function, and even fertility loss and early menopause. These problems are often highly associated with chemotherapy-induced ovarian damage in cancer treatment. However, there are no ideal treatment strategies at present. In our attempt to develop reagents and approaches for delaying ovarian aging and protecting chemotherapy-induced ovarian injury, we recently found that metformin may be the most promising drug to protect female malignant tumor patients from chemotherapy-induced ovarian injury. This trial aims to test whether administration of metformin during chemotherapy can protect the normal ovarian function of patients with early breast cancer.

      Methods

      This study is prospective, randomized, double-blind and placebo-controlled. Female patients with early breast cancer (N = 314) will be randomly assigned to two groups (placebo, metformin 2000 mg). Metformin will be administered during and after chemotherapy for patients with stage I-IIIa breast cancer. The primary outcome will be the menstruation recovery rate 12 months after chemotherapy, defined as recovery of menstruation twice in a row within 1 year. Patients will be followed up for 5 years to observe long-term ovarian function and prognosis, such as overall survival (OS), objective response rate (ORR), and disease-free survival (DFS). Quality of life and safety will also be assessed.

      Discussion

      Our research will provide a new treatment strategy for fertility protection, and clinical treatment guidance for cancer patients.

      Keywords

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