Triple-Negative Breast Cancer: Potential of Anti-Estrogen Therapies

Estrogens are known to stimulate tumor growth in breast cancer cells that contain their receptors. A recent study by Duke Cancer Institute discovered that estrogens also nourish the growth of breast tumors without receptors, as well as several other cancers. The study was published in the journal Science Advances(1^✔ ✔Trusted Source
Estrogen signaling suppresses tumor-associated tissue eosinophilia to promote breast tumor growth

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Researchers explain how estrogens limit immunotherapies’ efficiency in treating numerous malignancies, particularly triple-negative breast cancers, as well as the immune system’s capacity to attack tumors.

Improving Immunotherapy Efficacy in Aggressive Breast Cancer

Triple-negative breast cancers are a type of aggressive breast cancer that does not express the HER2 receptor proteins, progesterone, or estrogen.

Based on patient data and experiments conducted on mice, the researchers discovered that anti-estrogen drugs can counteract the effects of estrogens, enhancing the effectiveness of immunotherapies.

“The treatment for triple-negative breast cancer has been greatly improved with the advent of immunotherapy,” said senior author Donald McDonnell, Ph.D., professor in the Department of Medicine.

“Developing ways to increase the anti-cancer activity of immunotherapies is a primary goal of our research,” McDonnell said. “Here we have found a simple way to improve the effectiveness of immunotherapy for this type of breast cancer and the benefit was even seen in other cancers, including melanoma and colon cancers.”

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Role of Estrogen in Eosinophils and Tumor Growth in Breast Cancer

McDonnell and colleagues, McDonnell lab, focused on a type of white blood cell called eosinophils, which are typically activated during allergic reactions and inflammatory diseases.

Eosinophils have recently been identified as important in tumors, and a phenomenon called tumor associated tissue eosinophilia, or TATE, is associated with better outcomes among patients with multiple types of cancer, including colon, esophageal, gastric, oral, melanoma and liver cancers.

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In their studies, the Duke team described how estrogens decrease the number of eosinophils and TATE in mice. The hormone contributes to increased tumor growth in estrogen receptor-negative breast cancer tumors and melanoma tumors, which do not rely on estrogen receptors for tumor growth.

Conversely, anti-estrogen therapies inhibited estrogen receptor signaling and enhanced the efficacy of immunotherapies, slowing tumor growth.

“These findings highlight the importance of estrogen-receptor signaling as a regulator of eosinophil biology and TATE and highlight the potential near-term clinical application of anti-estrogen drugs to increase the benefits of immunotherapies in multiple tumor types,” McDonnell said.

He said clinical trials are being planned using an investigational anti-estrogen drug called lasofoxifene among patients with triple-negative breast cancers.

Reference:

1. Estrogen signaling suppresses tumor-associated tissue eosinophilia to promote breast tumor growth - https:www.science.org/doi/10.1126/sciadv.adp2442)

Source-Eurekalert