Open questions and controversies in the systemic treatment of breast cancer.

PURPOSE OF REVIEW: Personalized therapy has revolutionized our approach to breast cancer (BC). Patient selection strategies and new biomarkers are the basis for increasingly complex diagnostic and therapeutic algorithms. In this short review, we discuss recent developments in breast oncology, focusing on controversial topics with relevance for clinical practice. RECENT FINDINGS: The use of gene expression signatures to guide adjuvant therapy in hormone receptor-positive tumors and personalized strategies for systemic treatment of early stage HER2-positive disease represent significant advances. Additionally, the current role of platinum salts, immune checkpoint inhibitors, and CDK4/6 inhibitors in the (neo)adjuvant treatment remains controversial, with several ongoing randomized clinical trials exploring their use. In the metastatic disease setting, we identify important unmet needs such as the development of predictive biomarkers and the definition of the ideal sequencing algorithm with the incorporation of innovative agents in all subtypes of BC. SUMMARY: Advances in understanding the molecular biology and heterogeneity of BC have led to the development of new biomarkers and therapeutic agents that significantly impact current and future clinical practice.