Study Identifies Mechanism Which May Help Tamoxifen Work Better

Newswise — 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.

Co-authors of the study are principal investigator Paola Rizzo, Ph.D., department of pathology, Loyola University Chicago Stritch School of Medicine, Maywood, Ill.; Jieun Yun, department of biopharmaceutical sciences, University of Illinois at Chicago; Lu Hao, Oncology Institute, Loyola University Health System; Debra Tonetti, Ph.D., biopharmaceutical sciences, University of Illinois at Chicago; Albain; and Miele.

For more information on Loyola University Health System, log onto http://www.loyolamedicine.org

The 29th Annual San Antonio Breast Cancer Symposium meeting at the Henry B. Gonzalez Convention Center, San Antonio, Tex., runs through December 17, 2006.

Loyola University Health System, a wholly owned subsidiary of Loyola University Chicago (LUC), includes the private teaching hospital at Loyola University Medical Center (LUMC), 14 specialty and primary care centers in the western and southwestern suburbs, the Loyola Ambulatory Surgery Center at Oakbrook and the Loyola Oakbrook Terrace Imaging Center; and serves as co-owner-operator of RML Specialty Hospital, a long-term acute hospital specializing in ventilation weaning and other medically complex patients in suburban Hinsdale, Ill. Loyola is nationally recognized for its specialty care and groundbreaking research in cancer, neurological disorders, neonatology and the treatment of heart disease. The 61-acre medical center campus in Maywood, Ill., includes the 523-licensed bed Loyola University Hospital with a Level I trauma center, the region's largest burn unit, one of the Midwest's most comprehensive organ transplant programs, the Russo Surgical Pavilion and the Ronald McDonald® Children's Hospital of LUMC. Also on campus are Loyola's Center for Heart & Vascular Medicine, the Cardinal Bernardin Cancer Center, Loyola Outpatient Center and LUC Stritch School of Medicine. The medical school includes the Cardiovascular Institute, Oncology Institute, Burn & Shock Trauma Institute, Neuroscience Institute and the Neiswanger Institute for Bioethics and Health Policy.