Gene profile may predict sensitivity of cancer to treatment

Gene expression patterns may someday be used to predict breast cancer response to chemotherapy, according to a report in the August 2nd issue of The Lancet.

Moreover, Dr. Jenny C. Chang and colleagues at Baylor College of Medicine in Houston, Texas, found that sufficient RNA can be obtained from core biopsy samples to assess gene expression.Based on their findings, the study authors propose, “This type of molecular profiling could have important clinical implications in defining the optimum treatment for an individual patient, thus reducing the use of unproductive treatments, unnecessary toxicity, and overall cost.”The prediction is based a study of 24 patients with locally advanced breast cancer. The patients underwent four cycles of docetaxel every 3 weeks and were assessed after the fourth cycle prior to undergoing primary surgery. The investigators defined sensitive tumors as those that had no more than 25% residual disease based on tumor size. By this definition, 11 tumors were sensitive to docetaxel and 13 were resistant.Using microarray analysis, Dr. Chang’s group identified 92 genes that were differentially expressed in the specimens at p = 0.001. Fourteen genes were overexpressed in treatment-resistant tumors, while 78 were overexpressed in docetaxel-sensitive tissue. A “leave-one-out cross-validation procedure” revealed an 85% sensitivity and 90% specificity. Further validation was obtained from an independent set of six patients, all of whom exhibited sensitivity to docetaxel.However, Drs. James D. Brenton and Carlos Caldas of the University of Cambridge, UK, criticize this research because tumor volume may not be as clinically relevant as pathological response.In an interview with Reuters Health, Dr. Chang agreed with that, noting that the research is “preliminary and has to be confirmed.” In fact, she said, she and her colleagues are in the process of further examining their dataset, correlating their findings with histological response and other factors. They are also recruiting a large cohort of patients for a trial sponsored by the National Cancer Institute, Dr. Chang said. They will examine molecular profiles associated with response to other chemotherapeutic agents, and hope to conduct a similar analysis for other types of cancer.(Source: Lancet 2003;362:340-341,362-369: Reuters Health: Karla Gale: July 31, 2003: Oncolink)