Gene-expression signatures to inform neoadjuvant treatment decision in HR+/HER2− breast cancer: Available evidence and clinical implications

Over the last few years, the indication for chemotherapy use in HR+/HER2− early BC has been significantly modified by the introduction of gene-expression profiling. In the adjuvant setting, several gene-expression signatures have been validated to discriminate early stage HR+/HER2− BC with different prognosis and to identify patients for which adjuvant chemotherapy can be spared. Considering their ability to optimize the choice of adjuvant treatment and the increasing use of neoadjuvant approach in early BC, the potential use of gene-expression signatures to discriminate patients to be candidate to neoadjuvant chemotherapy or endocrine treatment appears particularly appealing. Indeed, the San Gallen Consensus Conference panel recently endorsed the use of genomic assays on core biopsies as a potential strategy for choosing the type of neoadjuvant treatment (chemotherapy or endocrine therapy) in selected patients. In this context, we here review evidence supporting the use of most common commercially available gene-expression signatures (Oncotype DX, MammaPrint, PAM50, EndoPredict and Breast Cancer Index) in patients receiving neoadjuvant therapy for HR+/HER2− BC. Data on the association of gene expression signatures and response to neoadjuvant chemotherapy or neoadjuvant endocrine therapy will be reviewed and the clinical implications of this data to guide the clinical decision-making process in early HR+/HER2− BC will be discussed.