Researchers at Fox Chase Cancer Center have identified an important gene involved in the spread of breast cancer that has developed resistance to long-term estrogen deprivation. The discovery was reported today in an oral presentation during the 97th Annual Meeting of the American Association for Cancer Research in Los Angeles. The gene may prove to be a useful marker for predicting which patients have the greatest risk of breast cancer recurrence so their doctors can offer the most appropriate treatment plan.
The research focused on breast cancer cells that had grown resistant to a class of anti-hormone drugs called aromatase inhibitors. AIs shut down an enzyme, aromatase, that lets the body produce estrogen outside the ovaries. These drugs represent one of the newest, most effective forms of hormone therapy for postmenopausal women whose breast cancer tests positive for estrogen receptors, which means that estrogen in the body fuels the growth of cancer cells.
"Unfortunately, one of the drawbacks to extended use of an AI may be that some of the cancer cells develop resistance to the drug and are able to grow and spread independent of estrogen," said Fox Chase Cancer Center biochemist Joan S. Lewis-Wambi, Ph.D, who presented the results of the study of aggressive AI-resistant breast cancer cells.
"Our laboratory has developed several AI-resistant breast cancer cell lines and have found that these cells are very invasive compared to AI-sensitive breast cancer cells," she explained. "Analyses of gene activity in these AI-resistant cells have shown that they express high levels of genes associated with invasiveness and metastasis."
The researchers found, however, that they could reverse this aggressive behavior by using molecules called "small interfering RNAs" to knock out the gene called CEACAM6 (carcinoembryonic antigen-related cell adhesion molecule 6).
"Overall, these findings identify CEACAM6 as a unique mediator of the aggressiveness and spread of AI-resistant breast cancer," Lewis-Wambi said. "This suggests that it might be an important biomarker for metastasis and a possible target for novel treatments for patients with metastatic breast cancer.
Lewis-Wambi's co-authors include Fox Chase scientific technician Helen R. Kim, V. Craig Jordan, OBE, Ph.D., D.Sc., vice president and research director for medical science at Fox Chase, and Heather Cunliffe, Ph.D., head of the breast and ovarian cancer research laboratory at Translational Genomics Research Institute in Phoenix, Ariz. The supercomputer at Translational Genomics performed the gene expression analyses for the study.
The Department of Defense Breast Cancer Program supports this research through a Center of Excellence grant to Fox Chase.