Predictive markers of endocrine response in breast cancer

Ongoing clinical and research efforts seek to optimise the use of endocrine therapy in the treatment of breast cancer. Accurate biomarkers are needed that predict response for individual patients. The presence of the estrogen receptor (ER) as the direct (for tamoxifen and fulvestrant) or indirect (for aromatase inhibitors) target molecule for endocrine therapy remains the foremost biomarker and determinant of response. However, ER expression only poorly predicts outcome and further indicators of response or resistance are required. The development and application of molecular signature assays such as Oncotype Dx, Prosigna, Mammaprint and Endopredict have provided valuable information on prognosis and these are being used to support clinical decision making on whether endocrine therapy alone alongside surgery is sufficient for ER-positive early stage breast cancers or whether combination of endocrine with chemotherapy are also warranted. Ki67, the proliferation marker, has been widely used in the neo-adjuvant (pre-operative) setting to help predict response and long term outcome. Gene expression studies within the same setting have allowed monitoring of changes of potential predictive markers. These have identified frequent changes in estrogen-regulated and proliferation genes. Specific molecules such as mutant ER may also prove helpful biomarkers in predicting outcome and monitoring response to treatment.