Gene Expression Signatures for Guiding Initial Therapy in ER+/HER2- Early Breast Cancer

In triple-negative (TNBC) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer patients, neoadjuvant systemic therapy is the standard recommendation for tumors larger than 2 cm. Monitoring the response to primary systemic therapy allows for the assessment of treatment effects, the need for breast-conserving surgery (BCS), and the achievement of pathological complete responses (pCRs). In estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer, the benefit of neoadjuvant strategies is controversial, as they have shown lower tumor downstaging and pCR rates compared to other breast cancers. In recent decades, several gene expression assays have been developed to tailor adjuvant treatments in ER+/HER2- early breast cancer (EBC) to identify the patients that will benefit the most from adjuvant chemotherapy (CT) and those at low risk who could be spared from undergoing CT. It is still a challenge to identify patients who will benefit from neoadjuvant systemic treatment (CT or endocrine therapy (ET)). Here, we review the published data on the most common gene expression signatures (MammaPrint (MP), BluePrint (BP), Oncotype Dx, PAM50, the Breast Cancer Index (BCI), and EndoPredict (EP)) and their ability to predict the response to neoadjuvant treatment, as well as the possibility of using them on core needle biopsies. Additionally, we review the changes in the gene expression signatures after neoadjuvant treatment, and the ongoing clinical trials related to the utility of gene expression signatures in the neoadjuvant setting.