Researchers identify potential new treatment for a subgroup of women with triple negative breast cancer

Researchers at the Mayo Clinic have identified the drug estradiol as a potential new treatment for a subgroup of women with triple negative breast cancer. Their conclusions are published in the Proceedings of the National Academy of Sciences.

"Triple negative breast cancer is a form of breast cancer lacking the expression of alpha receptors of estrogen, progesterone receptor and human epidermal growth factor receptor 2, also called HER2. it has high rates of disease recurrence, "says Hawse. Ph.D., molecular biologist at Mayo Clinic and lead author. "Until now, few drugs other than chemotherapy seem to be effective for treating this disease."

In previous research, Dr. Hawse and colleagues have found that a second form of the estrogen receptor, the so-called estrogen beta-receptor, accounts for about 25% of triple-negative breast cancer tumors. In this study, Dr. Hawse's lab demonstrated that estradiol, a natural female hormone, effectively inhibits the growth of triple-negative breast cancer tumors expressing the beta-estrogen receptor.

"Remarkably, we discovered that estradiol, which normally stimulates the growth of cancer cells in tumors expressing the estrogen receptor alpha, has the opposite effect of triple negative breast cancer," says the Dr. Hawse. "However, estradiol was only able to inhibit the growth of triple negative breast cancer only when the beta estrogen receptor was present."

Dr. Hawse and colleagues have discovered a potential mechanism for how estradiol exerts its anti-cancer effects. They determined that when estradiol binds to the beta-estrogen receptor in triple-negative breast cancer, it stimulates the expression of a group of proteins called "cystatin", which exhibit tumor suppressor effects on cancer cells nearby and distant.

On the basis of these data, researchers at the Mayo Clinic and the Breast Cancer Translational Research Consortium will soon open a Phase II clinical trial to test the efficacy of estradiol as a treatment. for women with triple negative metastatic breast cancer expressing beta estrogen receptors.

"Estradiol is FDA- [Food and Drug Administration] approved as a treatment for women with breast cancer; However, its use is generally limited to women with alpha-positive breast cancer with estrogen receptors that has become resistant to standard therapies, "said Matthew Goetz, MD, medical oncologist and co-investigator of Dr. Hawse. " We are excited to determine if oestradiol can be reused as a new triple negative breast cancer treatment that expresses beta-receptor estrogen. "

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More information:
Jordan M. Reese et al. ERβ-induced cystatin induction results in suppression of TGFβ signaling and inhibition of metastases of triple-negative breast cancer, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073 / pnas.1807751115