New Approach for ER-positive Breast Cancer | News | Loyola Medicine
Wednesday, December 10, 2014

Novel approach for estrogen-receptor-positive breast cancer looks promising

New class of drugs could help overcome resistance to standard treatments

MAYWOOD, Ill. (December 10, 2014) – Loyola University Medical Center 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 the Notch protein 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 medical oncologist and co-leader of Loyola’s Breast Cancer Research Program. “Our research suggests a potential role this new experimental drug class may have in optimizing existing endocrine therapies, such as tamoxifen and aromatase inhibitors, and in overcoming resistance to cancer drugs."

The Notch protein, which promotes tumor growth and survival, is present on the surface of cancer stem cells. The protein latches onto 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.

Researchers discovered 18 genes that are regulated by Notch and are significantly reversed by the addition of the GSI, even though it was a very short exposure. They also identified a gene called DAXX that is critical for stem cell survival, which was turned off by the GSI.

“Identifying these genes may help us predict which patients will respond well to the GSI anti-Notch therapy,” said Dr. Albain, who also is a professor in the Department of Medicine, Division of Hematology/Oncology at Loyola University Chicago Stritch School of Medicine.

There were minimal side effects reported in this study from either the GSI or the hormone therapy. One patient experienced puffy eyes and coughing and four patients experienced facial acne. No patients experienced diarrhea or surgical complications.

Researchers are planning a larger, phase II study to evaluate the efficacy of the GSI class of drugs added to endocrine therapy versus endocrine therapy alone. This study also will determine how well the 18-gene “signature” will predict who responds to therapy.

“This is an exciting new strategy to overcome resistance to a very common class of drugs (tamoxifen, letrozole), so it is our hope that in the future a vast number of patients with estrogen-receptor-positive breast cancer could benefit,” Dr. Albain said.

Other investigators involved with this study include: Cheryl M. Czerlanis, Shelly Lo, Patricia A. Robinson, Ellen Gaynor, Constantine Godellas, Davide Bova, Kathy Czaplicki, Barbara Busby, Patrick J. Stiff and Clodia Osipo (senior author) from Loyola; Andrei Y. Zlobin, Kyle R. Covington, Brian T. Gallagher, Susan G. Hilsenbeck and Suzanne A.W. Fuqua from Baylor College of Medicine Duncan Cancer Center; and Lucio Miele from Louisiana State University Cancer Center.

About Loyola Medicine and Trinity Health

Loyola Medicine, a member of Trinity Health, is a quaternary care system based in the western suburbs of Chicago that includes Loyola University Medical Center (LUMC), Gottlieb Memorial Hospital, MacNeal Hospital and convenient locations offering primary and specialty care services from 1,877 physicians throughout Cook, Will and DuPage counties. LUMC is a 547-licensed-bed hospital in Maywood that includes the William G. and Mary A. Ryan Center for Heart & Vascular Medicine, the Cardinal Bernardin Cancer Center, a Level 1 trauma center, Illinois's largest burn center, a certified comprehensive stroke center and a children’s hospital. Having delivered compassionate care for over 50 years, Loyola also trains the next generation of caregivers through its teaching affiliation with Loyola University Chicago’s Stritch School of Medicine and Marcella Niehoff School of Nursing. Gottlieb is a 247-licensed-bed community hospital in Melrose Park with 150 physician offices, an adult day care program, the Gottlieb Center for Fitness, the Loyola Center for Metabolic Surgery and Bariatric Care and the Loyola Cancer Care & Research at the Marjorie G. Weinberg Cancer Center at Melrose Park. MacNeal Hospital is a 374-bed teaching hospital in Berwyn with advanced inpatient and outpatient medical, surgical and psychiatric services, advanced diagnostics and treatments. MacNeal has a 12-bed acute rehabilitation unit, a 25-bed inpatient skilled nursing facility, and a 68-bed behavioral health program and community clinics. MacNeal has provided quality, patient-centered care to the near west suburbs since 1919.

Trinity Health is one of the largest multi-institutional Catholic healthcare systems in the nation, serving diverse communities that include more than 30 million people across 22 states. Trinity Health includes 94 hospitals, as well as 109 continuing care locations that include PACE programs, senior living facilities and home care and hospice services. Its continuing care programs provide nearly 2.5 million visits annually. Based in Livonia, Mich., and with annual operating revenues of $18.3 billion and assets of $26.2 billion, the organization returns $1.1 billion to its communities annually in the form of charity care and other community benefit programs. Trinity employs about 133,000 colleagues, including 7,800 employed physicians and clinicians. Committed to those who are poor and underserved in its communities, Trinity is known for its focus on the country's aging population. As a single, unified ministry, the organization is the innovator of Senior Emergency Departments, the largest not-for-profit provider of home health care services—ranked by number of visits—in the nation, as well as the nation’s leading provider of PACE (Program of All Inclusive Care for the Elderly) based on the number of available programs.