A French-speaking team has managed to better understand the role of two hormones in the development of tumours, with prospects for treatment.
Estrogen and progesterone are female hormones. Estrogen (ER) and progesterone (PR) receptors are found on or inside normal breast cells and some types of breast cancer cells. It is on these receptors that hormones bind to cells. Once attached, the hormones can affect the behavior or growth of the cells, explains the Canadian Cancer Society.
Breast cancer affects one in seven women and is the most commonly diagnosed cancer worldwide. Over 70% of all breast cancers are classified as estrogen positive based on detection of the estrogen receptor in at least 1% of tumor cells. Blocking this receptor is the classic target of hormone treatments, which have significantly improved patient survival rates.
Lack of models
The problem is that tumors that are estrogen receptor positive have been understudied because the field lacks suitable models. When we tried to grow breast cancers in genetically modified mice, “they were not hormone-responsive, and the success rates of estrogen receptor-positive breast cancer xenografts are extremely low,” says Professor Cathrin Brisken from the EPFL School of Life Sciences.
Previous studies have revealed an important interaction between the estrogen receptor and the progesterone receptor. However, the lack of suitable cell lines and animal models has prevented scientists from properly studying this interaction. Since the progesterone receptor gene is affected by the estrogen receptor, hormone treatments that target the latter can block the expression of the former. This complexity makes it difficult to study the role of each receptor independently and, therefore, to optimize treatment strategies.
Successful mouse transplant
Today, in collaboration with a research and medical team from the CHUV, the Réseau Lausannois du Sein and the ICPI (International Cancer Prevention Institute), Cathrin Brisken’s laboratory has successfully transplanted positive human breast cancer cells to the estrogen receptor on the milk ducts of immunocompromised mice. This breakthrough allowed them to study the effect of estrogen and progesterone on the development of breast cancer.
Scientists have discovered that these two hormones, estrogen and progesterone, can increase tumor growth, and that combined treatments can promote metastasis, and therefore the spread of cancer.
The progesterone receptor may be a target
But there is a way to deal with it. “We discovered that tumors react differently to the two hormones in different patients, which suggests that it is possible to improve treatment by adapting it,” explains Cathrin Brisken. “In addition, suppressing progesterone receptor expression may be a therapeutic option,” she adds. “While it was claimed that progesterone could help women with breast cancer, we show that this hormone promotes tumors and that the progesterone receptor mediates estrogen receptor signaling, making this receptor interesting as a potential therapeutic target.
The study, which was published in the journalNature Communications”, was also presented by the director of the Society of Endocrinology during the ENDO 2022 event bringing together more than 7000 doctors and scientists and which took place from June 11 to 14 in Atlanta, United States.