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Estradiol as Potential Treatment for Subset of Triple-Negative Breast Cancers


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Mayo Clinic researchers have identified estradiol as a potential new treatment for a subset of women with triple-negative breast cancer. Their findings were published by Reese et al in the Proceedings of the National Academy of Sciences of the United States of America.

John Hawse, PhD

John Hawse, PhD

“Triple-negative breast cancer is a form of breast cancer that lacks expression of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2, also known as HER2 … and it exhibits high rates of disease recurrence,” said senior author John Hawse, PhD, a molecular biologist at Mayo Clinic. “So far, there have been few drugs other than chemotherapy that appear to work effectively for the treatment of this disease.”

Estrogen Receptor β

In previous research, Dr. Hawse and his colleagues discovered that a second form of the estrogen receptor, known as estrogen receptor β, is expressed in approximately 25% of triple-negative breast cancer tumors. In this study, Dr. Hawse’s laboratory demonstrated that estradiol, a naturally occurring female hormone, effectively inhibits the growth of triple-negative breast cancer tumors expressing estrogen receptor β.

“Remarkably, we discovered that estradiol, which normally stimulates growth of cancer cells in tumors that express estrogen receptor α, has the opposite effect in triple--negative breast cancer,” says Dr. Hawse. “However, estradiol was only able to inhibit the growth of triple-negative breast cancer when estrogen receptor β was present.”

Dr. Hawse and his colleagues discovered one potential mechanism of how estradiol exerts its anticancer effects. They determined that when estradiol binds with estrogen receptor β in triple-negative breast cancer, it stimulates the expression of a group of proteins called cystatins, which exhibit tumor-suppressing effects on neighboring and distant cancer cells.

Matthew Goetz, MD

Matthew Goetz, MD

Based on these data, researchers at Mayo Clinic and the Translational Breast Cancer Research Consortium will soon open a phase II clinical trial to test the effectiveness of estradiol as a treatment for women with metastatic triple-negative breast cancer that expresses estrogen receptor β.

“Estradiol is U.S. Food and Drug Administration–approved as a treatment for women with breast cancer; however, its use is typically limited to women with estrogen receptor α–positive breast cancer that has become resistant to standard therapies,” said Matthew Goetz, MD, a medical oncologist and co-investigator with Dr. Hawse. “We are excited to study whether estradiol can be repurposed as a new treatment for triple-negative breast cancer that expresses estrogen receptor β.” 

Reese JM, et al: Proc Natl Acad Sci U S A 41:E9580-E9589, 2018.


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