Gene-Expression Profiling and the Future of Adjuvant Therapy

Learning Objectives After completing this course, the reader will be able to:Explain how clinical experience influences treatment selection and how this is likely to be refined by molecular diagnosis in the future.Describe the potential of gene profiling in personalized cancer medicine.Discuss some of the limitations of clinical medicine as it relates to the rapid application of gene-expression profiling. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com Gene-expression profiling can help distinguish between patients at high risk and those at low risk for developing distant metastases, and so identify patients for adjuvant therapy. For several years, the Netherlands Cancer Institute has been working on gene-expression profiling of breast cancer using a microarray platform containing 25,000 genes. Using supervised classification, a prognostic classifier consisting of 70 genes could be identified. In addition to providing prognostic information, gene profiling should also enable us to detect patients who are likely to respond to particular adjuvant interventions. Well-known predictors for response to systemic therapy include estrogen receptor status HER-2 status, c-kit mutation, and epidermal growth factor receptor mutation. Because of the long periods required for predicting responsiveness in the adjuvant setting, neoadjuvant trials promise far quicker results. Several neoadjuvant studies are under way or planned to investigate gene-expression profiling as a means of predicting the therapeutic response to doce taxel (Taxotere®; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com), paclitaxel (Taxol®; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com), cyclophosphamide, and doxorubicin (Adriamycin®; Bedford Laboratories, Bedford, OH, http://www.bedfordlabs.com) in breast cancer patients. It is expected that in the coming years an increasing number of novel prognostic and predictive tests will help in guiding the adjuvant systemic treatment of breast cancer and other malignancies.