Clinical application of genomic profiling in breast cancer and the TAILORx trial

Breast cancer is characterized by clinical and molecular heterogeneity. Microarray-based gene expression has identified distinct expression profiles associated differing prognosis and response to therapy. Newer technologies now permit evaluation not only of gene expression, but also single nucleotide polymorphisms, gene copy number, genomic mutations, and epigenomic or microRNA patterns that modulate gene expression. These state-of-the-art molecular approaches offer new insights into the pathogenesis of breast cancers, and offer the promise to improve the prevention, diagnosis, and management of the disease. Although many gene expression assays have been shown to provide prognostic information that is complementary to classical clinicopathologic features, the clinical utility of such assays is uncertain — that is, how do the results alter patient care, and do patients benefit from that change? Most attention has focused on using these assays to reduce overtreatment in patients with estrogen-receptor positive, lymph node negative breast cancer, which accounts for about one-half of all breast cancers, and about 8% of all cancers in the United States. Evidence suggest that some assays do have clinical utility when used appropriately, usually by reducing overtreatment with chemotherapy in patients who may otherwise have an excellent prognosis with local therapy plus endocrine therapy alone — or “treatment sparing”. Other potential examples of clinical utility include “treatment selection” (selecting individuals for chemotherapy when standard clinicopathologic features would have suggested otherwise) and “treatment direction” (selecting individuals for chemotherapy when clinicopathologic features suggested therapeutic equipoise). There are three breast cancer clinical trials which have integrated multiparameter assays into the clinical decision making, including the TAILORx and CHORUS trials (which use the 21 gene assay) and the MINDACT trial (which uses the 70 gene assay). The results of these trials will inform us regarding the clinical utility of these assays, and provide a valuable resource for evaluating other clinical cancer tests in the future.