NEW YORK (Reuters Health) - Multiple genetic markers appear to be potentially useful in predicting pathologic complete response to chemotherapy prior to surgery for breast cancer, researchers report in the June 15th issue of the Journal of Clinical Oncology.
The results, senior investigator Dr. Lajos Pusztai told Reuters Health, “suggest that it will be possible in the near future to develop chemotherapy regimen-specific predictors of response to therapy.”
Dr. Pusztai and colleagues at the University of Texas M. D. Anderson Cancer Center, Houston, note that “currently there is no clinically useful molecular predictor of response to any cytotoxic drug used in the treatment of breast cancer.”
To help develop a predictor of pathologic complete response, the researchers studied 42 women with breast cancer who were about to undergo weekly neoadjuvant chemotherapy with paclitaxel and fluorouracil with doxorubicin and cyclophosphamide.
All underwent fine needle aspiration to obtain tumor RNA before chemotherapy began. In total, results in 24 patients were used as “training cases” for marker discovery, and the remaining 18 for independent validation.
In total, 31% of patients experienced complete disappearance of all invasive cancer in breast - pathologic complete response - after completion of chemotherapy. Of these, 6 patients were in the discovery group and 7 were in the validation group.
No single marker was predictive of response, but using data from the discovery samples, the researchers built a multigene model using 74 markers and tested it on the validation samples.
Overall, there was a 78% predictive accuracy and a 100% positive predictive value for pathologic complete response, a 73% negative predictive value , a sensitivity of 43% and a specificity of 100%.
These findings, Dr. Pusztai stressed “show the feasibility and a potentially clinically useful prediction accuracy, but it is not the final diagnostic test. It’s promising, but needs further work.”
In an accompanying editorial, Dr. Matthew Ellis of Washington University, St. Louis and Dr. Karla Ballman of the Mayo Clinic Cancer Center, Rochester, Minnesota, agree by observing that “for [pathologic complete response] tumors there is no evidence that the predictor is better than guessing.”
However, they do conclude that the study “should be viewed as an instructive pilot effort.”
Source: J Clin Oncol 2004;22:2284-2293:2267-2269. [ Google search on this article ]
MeSH Headings: Biological Sciences : Biology : Breast Neoplasms : Environment and Public Health : Epidemiologic Methods : Genetics : Health : Health Occupations : Health Services Administration : Mathematics : Medicine : Investigative Techniques : Neoplasms : Neoplasms by Site : Pharmacogenetics : Physical Sciences : Population Characteristics : Predictive Value of Tests : Preventive Medicine : Probability : Public Health : Quality of Health Care : Sensitivity and Specificity : Specialties, Medical : Statistics : Epidemiologic Research Design : Health Care Quality, Access, and Evaluation : Health Care Evaluation Mechanisms : Analytical, Diagnostic and Therapeutic Techniques and Equipment : Biological Sciences : Diseases : Health Care : Physical Sciences Copyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
