Better choice of contraceptives can prevent breast cancer
Hormonal contraceptives, such as the pill, patch, and vaginal ring, contain synthetic hormones that prevent pregnancy by stopping ovulation, changing cervical mucus to prevent sperm from passing through the cervix, and finding an egg, or changing the lining of the uterus to prevent a fertilized egg from being implanted there.
Despite their widespread use, hormonal contraceptives are known to increase the risk of breast cancer, which is the most common cause of cancer death in women worldwide, and also tops the list of most commonly diagnosed cancers. in 2020.
The main component of hormonal contraceptives are progestins, which mimic progesterone, a female sex hormone. Progesterone is involved in a number of biological processes, including the menstrual cycle, pregnancy, and various aspects of fetal development, such as brain programming.
Now, a team of scientists led by Professor Cathrin Brisken from EPFL’s School of Life Sciences has taken a close look at the different biological effects of different progestins in hormonal contraceptives on breast tissue – the mammary epithelium. The work is published in EMBO molecular medicine.
“While we know how different contraceptive formulations affect the cardiovascular system, we know little about their effects on the breast,” Brisken says. “So we developed new approaches to compare the most commonly used progestins in different hormonal contraceptives and were surprised to find that some of them stimulate cell proliferation in the breast – while others do not. “
Researchers tested the effects of prolonged exposure to different progestins on human breast epithelial cells, or HBECs, which line the inner layer of the breast. To do this, they developed “humanized” mouse mammary glands by grafting mammary epithelial cells from human breast tissue donated from reduction mammoplasty samples into animal milk ducts and monitoring their growth in vivo. .
“We found that HBECs graft and proliferate in mouse milk ducts, maintaining hormone receptor expression and hormonal reactivity, which are crucial factors in establishing a relevant preclinical model and thus fostering translational research,” explains Brisken.
The team realized that what distinguished the stimulating and harmless progestins were their “androgenic properties” – a technical term for substances that trigger the development of male characteristics, such as body hair, muscle mass, and so on. It’s not as strange as it sounds: progesterone, mainly known as the female hormone, is used for the production of the famous male hormone testosterone in both women and men.
Some progestins have androgenic properties, acting like testosterone; some actually block them. The key is a protein known as the androgen receptor, which, when activated by an androgen progestin, travels to the nucleus of the cell where it regulates the expression of certain genes.
Working with epithelial cells from a mouse model, researchers found that progestins androgens act through the androgen receptor to induce the expression of the Rankl protein, which plays an important role in cell proliferation in the mammary epithelium. . This effect has not been observed with antiandrogen progestins.
The study showed that androgenic progestins – but not antiandrogenics – promote cell proliferation. “Exposure of human breast epithelia to androgenic progestins for long periods of time has caused hyperproliferation and changes in cells that are associated with early and pre-malignant lesions – at least in xenografted human breast epithelia,” explains From Martino.
“Hormonal contraception exposes women to different progestins with or without estrogen,” Brisken explains. “The androgenic properties of progestins determine their biological activity in the mammary epithelium and reveal an unexpected role for androgen receptor activity in the proliferation of breast epithelial cells.”
The crux of the study is that progestins with anti-androgenic activity may be a safer option with regard to breast cancer risk than compounds linked to testosterone, for example the widely used contraceptive levonorgestrel (” Plan B”). “It may be possible to prevent breast cancer associated with contraception by making more informed choices taking into account the molecular makeup of a contraceptive,” Brisken concludes.
Lausanne University Hospital Center (CHUV)
International Institute for Cancer Prevention
Swiss National Science Foundation
Swiss Cancer League
Biltema Foundation ISREC Cancera Stiftelsen
Mats Paulssons Stiftelse
Stitelsen Stefan Paulssons Cancerfond
Joint Action and Learning Initiative (JALI)
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