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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References
- Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin. 2018; 68: 394-424
The latest National Cancer report in 2018, China national cancer center.
- How do chemotherapeutic agents damage the ovary?.Hum. Reprod. Update. 2012; 18: 525-535
- Fertility issues in adolescent and young adult cancer survivors.J. Adolesc. Young Adult Oncol. 2016; 5: 48-57
- The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE).Lancet. 2017; 390: 2569-2582
- Impact of cancer therapies on ovarian reserve.Fertil. Steril. 2012; 97 (p. 134-40 e1)
- Anticancer chemotherapy in teenagers and young adults: managing long term side effects.BMJ. 2016; 354 (p. i4567)
- Metformin prevents murine ovarian aging.Aging. 2019; 11: 3785-3794
- Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer.Nature. 2018; 559: 637-641
- Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism.Cell. 2013; 153: 228-239
- Metformin reverses established lung fibrosis in a bleomycin model.Nat. Med. 2018; 24: 1121-1127
- Metformin targets mitochondrial electron transport to reduce air-pollution-Induced thrombosis.Cell Metab. 2018; (p. S1550-4131(18)30586-2)
- Metformin alters upper small intestinal microbiota that impact a glucose-SGLT1-sensing glucoregulatory pathway.Cell Metab. 2018; 27: 101-117
- Metformin increases survival in hormone receptor-positive, HER2-positive breast cancer patients with diabetes.Breast Cancer Res. 2015;
- Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes.Cancer. 2011; 117: 5103-5111
- Metformin therapy for the reproductive and metabolic consequences of polycystic ovary syndrome.Diabetologia. 2017; 60: 1656-1661
- Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: a double-blind, randomized, placebo-controlled study.Am. J. Psychiatry. 2012; 169: 813-821
- Metformin prevents murine ovarian aging.Aging (Albany NY). 2019; 10 (p. 11)
- Risk of chemotherapy-induced amenorrhea in patients with breast cancer: a systematic review and meta-analysis.Acta Oncol. 2016; 55
Article info
Publication history
Published online: April 21, 2020
Accepted:
April 14,
2020
Received in revised form:
March 26,
2020
Received:
February 2,
2020
Identification
Copyright
© 2020 Published by Elsevier B.V.
