Novel approach for estrogen-receptor-positive breast cancer reported

PUBLIC RELEASE DATE:

10-Dec-2014

Contact: Nora Dudley nodudley@lumc.edu 708-216-6268 Loyola University Health System @LoyolaHealth

Loyola researchers and collaborators have reported promising results from a novel therapeutic approach for women with estrogen-receptor-positive breast cancer.

The new approach, a new drug class called gamma secretase inhibitors (GSI), specifically inhibits Notch and shuts down critical genes and cancer cells responsible for tumor growth.

Kathy Albain, MD, FACP, who led the study, will present findings Dec. 11 during the 2014 San Antonio Breast Cancer Symposium.

Existing cancer drugs are effective in killing mature breast cancer cells. But a handful of immature breast cancer stem cells are resistant to such drugs. They survive and are responsible for tumor growth and progression. Resistance to standard therapy is a major cause of death in women with estrogen-receptor-positive breast cancer. Approximately 75 percent of breast cancers are estrogen-receptor positive.

"New treatments are desperately needed for women with estrogen-receptor-positive breast cancer who develop resistance to standard therapies," said Dr. Albain, a professor in the Department of Medicine, Division of Hematology/Oncology at Loyola University Chicago Stritch School of Medicine. "Our research suggests a potential role this new experimental drug class may have in optimizing existing endocrine therapies, such a tamoxifen and aromatase inhibitors, and in overcoming resistance to cancer drugs."

The Notch protein promotes tumor growth and survival. The protein is present on the surface of cancer stem cells. The protein latches on to other cells, and the resulting "molecular handshake" activates various genes in the stem cells that drive tumor growth, spread and survival. Activating these genes, in effect, makes the stem cells resistant to common cancer drugs. A pilot study conducted at Loyola found that the GSI appears to block this process by turning off key genes.

The purpose of the study was to identify critical genes involved in the process. The study included 20 patients with early-stage, estrogen-receptor-positive breast cancer. Prior to surgery, the patients received one of two commonly used drugs, tamoxifen or letrozole, for 14 days to block the estrogen stimulation of breast cancer cells. They underwent a biopsy on day 14. They then received the GSI, MK-0752, plus continued one of two standard drugs, tamoxifen or letrozole. Patients underwent their definitive breast cancer surgery on day 25 and part of this tumor was provided as well for this research.

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Novel approach for estrogen-receptor-positive breast cancer reported