Progesterone from ovulatory menstrual cycles is an important cause of breast cancer

Breast Cancer Research

Perspective

V. Craig Jordan¹  Tommaso Simoncini²  Robert D. Langer³  Ludwig Kiesel⁴  Kirsten Kluivers⁵  Marcus Schmidt⁶  Frank Z. Stanczyk⁷  Kristina Gemzell-Danielsson⁸  Jan Krijgh⁹  Herjan J. T. Coelingh Bennink⁹  Iman J. Schultz⁹  Paula Briggs^1,10  Jan F. M. Egberts^1,11 

[1]Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

[2]Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

[3]Department of Family Medicine and Public Health, University of California San Diego School of Medicine, San Diego, CA, USA

[4]Department of Gynaecology and Obstetrics, University of Münster, Münster, Germany

[5]Department of Obstetrics and Gynaecology, Radboud University Medical Centre, Nijmegen, The Netherlands

[6]Department of Obstetrics and Gynaecology, University Medical Center Mainz, Mainz, Germany

[7]Department of Obstetrics and Gynaecology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA

[8]Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden

[9]Pantarhei Bioscience BV, P.O. Box 464, 3700 AL, Zeist, The Netherlands

[10]Sexual and Reproductive Health, Liverpool Women’s NHS Foundation Trust, Liverpool, UK

[11]Terminal 4 Communications, Hilversum, The Netherlands

关键词: Breast cancer;    Menstrual cycles;    Progesterone;    Estrogens;    Tumor doubling time;    DNA replication;    WNT4;   

DOI  :  10.1186/s13058-023-01661-0

 received in 2023-02-01, accepted in 2023-05-22,  发布年份 2023

来源: Springer

【 摘 要 】

Many factors, including reproductive hormones, have been linked to a woman’s risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman’s lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.

【 授权许可】

CC BY   
© The Author(s) 2023

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