RPCI Researchers Seeing Links Between Genetic Profile, Trastuzumab Resistance
Trastuzumab interferes with a protein, known as the HER2 receptor, that’s linked to breast cancer. But because a high number of breast cancer patients — approximately 50 percent — don’t respond to the drug and experience disease progression or recurrence, there’s great interest in research that might uncover the factors driving those responses.
Over the last two years, the Roswell Park team has looked at 41 breast carcinoma cases in which amplified HER2 levels were seen and for which fresh frozen tissue was available. Of these patients, 12 were treated with trastuzumab; three of them (25%) experienced recurrence. Among the 11 not treated with the drug, six (55%) had recurrence.
Gene microarrays were used to identify differentially expressed genes for trastuzumab — responsive vs. resistant.
The Roswell Park team found that the differentially expressed genes for recurrence or non-recurrence were distinct between the group treated with trastuzumab and the group that was not treated with that therapy. While the trastuzumab-treated differentially expressed genes were enriched for genes involved in nucleic acid binding, the trastuzumab-untreated profile was enriched in immunity and defense.
Dr. Khoury and his team hope that differential expression of key genes identified in this study may offer insights into trastuzumab resistance among breast cancer patients, and might in fact emerge as potential biomarkers for diagnosis, prognosis and treatment.
“The group who were treated with trastuzumab and developed recurrence had a genetic makeup different from those who were not treated and developed recurrence,” says Dr. Khoury, an Assistant Professor in the Department of Pathology & Laboratory Medicine at Roswell Park.
The team will now focus on those patients who were treated with trastuzumab. “The idea from the beginning,” says Dr. Khoury, “was to know why these patients who are treated with trastuzumab develop recurrence and why the others did not. There is definitely something going on, and we’re starting to understand these mechanisms.”
The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Roswell Park, founded in 1898, was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit Roswell Park’s website at http://www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email AskRoswell@Roswellpark.org.
Editor’s note: Dr. Khoury will present the results of the study, “Breast carcinoma with amplified HER2: A gene expression signature specific for trastuzumab resistance and poor prognosis,” June 5 from 2pm to 6pm as part of the Local-Regional and Adjuvant Therapy general poster session at ASCO’s 2010 meeting at McCormick Place Convention Center, S Hall A2.
Annie Deck-Miller, Senior Media Relations Manager