Using Breast Cancer Gene Expression Signatures in Clinical Practice: Unsolved Issues, Ongoing Trials and Future Perspectives

SIMPLE SUMMARY: Gene expression signatures were initially developed to take into account tumor biology for adjuvant chemotherapy decision and have become a standard option in hormone receptors-positive/HER2-negative early breast cancer. While recent randomized phase III studies have provided high level evidence to support their use, much more remains to be explored. This prospective review highlights the unsolved issues regarding targeted populations, delineates the best clinical indications and addresses questions that ongoing and future trials will have to meet. Apart from adjuvant chemotherapy indications, we review their potential interest to tailor neoadjuvant systemic treatments, adjuvant radiation therapy, extended adjuvant hormone therapy and CDK4/6 inhibitor adjuvant treatment. ABSTRACT: The development of gene expression signatures since the early 2000′s has offered standardized assays to evaluate the prognosis of early breast cancer. Five signatures are currently commercially available and recommended by several international guidelines to individualize adjuvant chemotherapy decisions in hormone receptors-positive/HER2-negative early breast cancer. However, many questions remain unanswered about their predictive ability, reproducibility and external validity in specific populations. They also represent a new hope to tailor (neo)adjuvant systemic treatment, adjuvant radiation therapy, hormone therapy duration and to identify a subset of patients who might benefit from CDK4/6 inhibitor adjuvant treatment. This review will highlight these particular issues, address the remaining questions and discuss the ongoing and future trials.