Genomic Signatures in Breast Cancer: Limitations of Available Predictive Data and the Importance of Prognosis

Several biomarkers and gene mutations in breast cancer have been shown to be predictive, in that they determine which treatments a patient should receive. Ideally, predictive markers would be available that could determine the most appropriate treatment plan based on a patient's biology. This goal is becoming a reality in some treatment settings and cancer types, with the increasing use of targeted therapies directed against specific molecular abnormalities. Immunohistochemistry (IHC) testing is in standard use for guiding breast cancer therapy. Testing for the estrogen receptor (ER) and progesterone receptor (PR) guides the use of endocrine therapy, and human epidermal growth factor receptor 2 (HER2) testing guides the use of HER2-targeted therapies. Although IHC provides some discrimination among breast cancer subsets and helps identify appropriate therapy, more information can be gained through gene expression analyses. Contemporary multianalyte assays have demonstrated greater precision and reproducibility than seen with IHC-based assays. The most important contribution of multigene assays is the identification of women with ER/PR-positive, HER2-negative, early-stage breast cancer who are at low risk of recurrence and therefore will likely do well with endocrine therapy alone. These patients can be safely spared from the cytotoxic effects of chemotherapy.