The study shows that better birth control methods can prevent breast cancer
Hormonal contraceptives, e.g. Hormones such as the pill, patch, and vaginal ring contain synthetic hormones that prevent pregnancy by either stopping ovulation, changing cervical mucus to prevent sperm from getting through the cervix and finding an egg, or changing the lining of the uterus to prevent a fertilized egg from being implanted into it.
Despite their widespread use, hormonal contraceptives are known to increase the risk of breast cancer, which is the leading cause of cancer-related death in women worldwide, and tops the list of most diagnosed cancers in 2020.
The main component of hormonal contraceptives are progestins, which mimic the female sex hormone progesterone. Progesterone is involved in a number of biological processes including the menstrual cycle, pregnancy, and various aspects of fetal development such as: B. brain programming.
Now, a team of scientists led by Professor Cathrin Brisken at the School of Life Sciences at EPFL has thoroughly and precisely examined the various biological effects that various progestins in hormonal contraceptives have on breast tissue – the breast epithelium. The work is published in EMBO Molecular Medicine.
While we know how different birth control formulations affect the cardiovascular system, little is known about their effects on the chest. 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 breast cell proliferation – others don’t. “
Cathrin Brisken, professor at the School of Life Sciences at the Ecole Polytechnique FÃ©dÃ©rale de Lausanne
The researchers tested the effects of prolonged exposure to various progestins on human breast epithelial cells, or HBECs, that line the inner breast layer. For this purpose, they developed “humanized” mammary glands of mice by transplanting breast epithelial cells from donated human breast tissue from reduced mammoplasty samples into the milk ducts of the animals and monitoring their growth in vivo.
“We found that HBECs transplant and reproduce in the milk ducts of mice, while maintaining hormone receptor expression and hormone reactivity. These are critical factors in establishing a relevant preclinical model and thus in promoting translational research,” says Brisken.
The team realized that the stimulant and harmless progestins were differentiated by their “androgenic properties” – a technical term for substances that trigger the development of male characteristics, such as body hair, muscle mass, etc. This is not as strange as it sounds: progesterone, mostly known as the female hormone, it is used in both women and men to make the famous male hormone testosterone.
Some progestins have androgenic properties and act like testosterone. Some actually block them. The key is a protein known as the androgen receptor that, when activated by an androgenic progestin, enters the cell nucleus and regulates the expression of certain genes there.
When working with the epithelial cells in a mouse model, the researchers found that androgenic gestagens induce the expression of the protein Rankl via the androgen receptor, which plays an important role in cell proliferation in the breast epithelium. This effect was not observed with antiandrogenic progestins.
The study showed that androgenic – but not antiandrogenic – gestagens promote cell proliferation. “Prolonged exposure of human breast epithelium to androgenic progestins resulted in hyperproliferation and changes in the cells associated with early premalignant lesions – at least in xenografted human breast epithelia,” says De Martino.
“Hormonal contraception exposes women to various progestins with or without estrogen,” says Brisken. “The androgenic properties of progestins determine their biological activity in the breast epithelium and show an unexpected role for androgen receptor activity in the proliferation of breast epithelial cells.”
The key finding of the study is that progestins with antiandrogenic activity may be a safer option in terms of breast cancer risk than testosterone-related compounds, e.g. B. the widely used contraceptive levonorgestrel (“Plan B”). “It might be possible to prevent breast cancer-related birth control by making more informed decisions based on the molecular makeup of a contraceptive,” concludes Brisken.
Ecole Polytechnique FÃ©dÃ©rale de Lausanne
Shamseddin, M., et al. (2021) Contraceptive progestins with androgenic properties stimulate the proliferation of breast epithelial cells. EMBO Molecular Medicine. doi.org/10.15252/emmm.202114314.