A new study by researchers at Georgetown’s Lombardi Comprehensive Cancer Center
may have implications for the thousands of breast cancer patients who develop resistance to antiestrogen drugs such as Tamoxifen®
. The work is published in the June 1 issue of Cancer Research
The study, led by Robert Clarke, Ph.D., D.Sc., professor of oncology, shows that there may be an association between the gene IRF 1 (Interferon Regulatory Factor) and breast tumor resistance to tamoxifen or other antiestrogen treatments. IRF 1 is a tumor suppressor gene not previously associated with breast cancer.
“We hope that by pinpointing the connection between IRF 1 and breast cancer, we may be able to better identify which patients will respond to antiestrogen treatment and which patients will ultimately develop antiestrogen resistance,” said Clarke.
Antiestrogen therapy is currently the most effective means to manage hormone-dependent breast cancer and has the fewest serious side effects. Hormone-dependent breast cancer accounts for approximately one-third of all breast cancer cases. The most widely prescribed antiestrogen therapy is tamoxifen, which blocks the activity of the estrogen hormone in breast tissue and can increase patients’ overall survival. However about a third of breast tumors that might be expected to respond (because they express receptors for estrogen) are resistant to antiestrogens from the onset of treatment, and many initially responsive tumors sooner or later become resistant.
The Lombardi researchers studied a series of antiestrogen-sensitive and antiestrogen-resistant human breast cells using a variety of different microarray technologies.
"The logical implication of our work is that by adding the protein interferon to antiestrogen therapy, we should be able to turn on the IRF 1 gene to make these tumors sensitive to antiestrogen therapy, hopefully inhibiting new breast cancers or reoccurrences of disease," said Clarke.
Clarke and his Georgetown colleagues will next use preclinical studies to test the effects of adding interferon to tamoxifen treatment. “Used as a primary treatment, interferon can be extremely toxic, so we will need to carefully study doses and timing of drug delivery before this can be tested in patients,” said Clarke.
“We would hope to be able to give low doses of interferon to induce IRF 1 and sensitize the tumors – we are not looking to add enough interferon to get its effects as a single agent,” said Clarke.
Co-authors of the study, which was funded by the National Cancer Institute, are Kerrie B. Bouker, Todd C. Skaar, David R. Fernandez, Kerry A. O'Brien, Rebecca B. Riggins, and Donghua Cao.