Better choice of contraceptives can prevent breast cancer


Stereofluorescence micrograph of a mouse mammary gland injected intraductally with normal human breast epithelial cells. Credit: Marie Shamseddin (EPFL).

Hormonal contraceptives, such as the pill, patch, and vaginal ring, contain synthetic hormones that prevent pregnancy, either by stopping ovulation, changing cervical mucus to prevent sperm from passing through the cervix, and finding a egg or change the lining of the uterus to prevent a fertilized egg from being implanted.

Despite its widespread use, it is known to increase the risk of breast cancer, which is the most common cause of cancer death among women around the world, and which also ranks on 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 various 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 of the EPFL School of Life Sciences, has looked closely at the different biological effects that different progestins of hormonal contraceptives have 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 the effects on the breast,” says Brisken. “Therefore, we developed new approaches to compare the most commonly used progestins in different hormonal contraceptives and were surprised that some of them stimulated cell proliferation in the breast, while others did not.”

Researchers tested the effects of prolonged exposure to different progestins on human breast epithelial or HBEC, which cover the inner layer of the chest. To do so, they developed “humanized” mouse mammary glands by grafting mammary epithelial cells from human donations. from mammoplasty samples of reduction in the milk ducts of animals and monitoring of their growth in vivo.

“We found that HBECs grow and proliferate in mouse milk ducts, maintaining hormone receptor expression and hormonal response capacity, which are crucial factors in establishing a relevant preclinical model and therefore in fostering translational research. “says Brisken.

The team realized that what distinguished stimulant and innocuous progestogens was their androgenic properties, a technical term for substances that trigger the development of male characteristics, such as body hair, muscle mass, and so on. This is not as strange as it sounds: progesterone, known primarily as a female hormone, is used for the production of the famous male hormone testosterone in both women and men.

Some progestins have androgenic properties, which act like testosterone; some actually block them. The key is a protein known as , which, when activated by an androgen , travels to the nucleus of the cell where it regulates the expression of certain genes.

Working with epithelial cells in a mouse model, the researchers found that androgenic progestins act through the androgen receptor to induce the expression of the Rankl protein, which plays an important role in cell proliferation. of the mammary epithelium. This effect was not seen with anti-androgenic progestins.

The study showed that they promote androgenic but not anti-androgenic progestins . “Exposure of the human breast epithelium to androgenic progestins over extended periods of time caused hyperproliferation and changes in cells associated with early malignant precocious lesions, at least in xenografted human breast epithelia,” he says De Martino.

“Hormonal contraception exposes women to different progestins with or without estrogen,” Brisken says. “The androgenic properties of progestins determine this in the mammary epithelium and reveal an unexpected role of androgen receptor activity in breast proliferation . “

The crucial view of the study is that progestins with anti-androgenic activity may be a safer option in terms of breast cancer risks than testosterone-related compounds, for example, the widely used contraceptive levonorgestrel (“Plan B “). “It may be possible to prevent cancer associated with contraception by making more informed decisions taking into account the molecular composition of a contraceptive, ”concludes Brisken.

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More information:
Marie Shamseddin et al, Contraceptive progestins with androgenic properties stimulate the proliferation of mammary epithelial cells, EMBO Molecular Medicine (2021). DOI: 10.15252 / emmm.202114314

Citation: Better Choice of Contraceptives Can Prevent Breast Cancer (2021, May 28), Retrieved May 29, 2021 at .html

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