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Study Identifies Mechanism Which May Help Tamoxifen Work Better

The “crosstalk” between estrogen and a special protein responsible for cell development (Notch) helps breast cancer cells// proliferate and spread, a new study shows.

“Breast cancer cells respond to loss of estrogen, which is caused by commonly used hormonal therapy, by increasing the Notch signal,” said senior study investigator Dr. Lucio Miele, professor, departments of pathology, pharmacology and experimental therapeutics, Loyola University Chicago Stritch School of Medicine, Maywood, Ill. “This helps the cancer cells survive the loss of estrogen.

“Blocking the Notch pathway with a Notch inhibitor offers a new strategy to stopping breast cancer,” said Miele, director, breast cancer basic science program, Cardinal Bernardin Cancer Center, Loyola University Health System. He presented the findings here today at the 29th annual San Antonio Breast Cancer Symposium.

Notch inhibitors are currently in early human clinical trials.

“Results of our study shows that in estrogen receptor positive cancers, a drug which inhibits the Notch protein should be used in combination with estrogen inhibitors,” said Miele. “In estrogen receptor negative cancers, the Notch inhibitor can be used alone or with chemotherapy.”

A significant number of people currently become resistant to the breast cancer drug tamoxifen. “For tamoxifen to work better, you need to inhibit the Notch pathway,” said co-author Dr. Kathy S. Albain, professor, division of hematology/oncology, department of medicine, Loyola University Chicago Stritch School of Medicine.

“This can be done by using a novel drug to block the Notch pathway while simultaneously controlling estrogen signaling through the estrogen receptor,” said Albain, director, thoracic oncology clinical research program; director, breast clinical research program; and co-director, multidisciplinary breast oncology center; Loyola University Health System, Maywood, Ill.

Albain also said this research suggests new therapeutic strategies for women with breast cancer.

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