Therapeutic advances in breast cancer have significantly improved outcomes in recent decades. In the early setting, there has been a gradual shift from adjuvant-only to neoadjuvant strategies, with a growing focus on customizing post-neoadjuvant treatments through escalation and de-escalation based on pathologic response. At the same time, the transition from a pre-genomic to a post-genomic era, utilizing specific assays in the adjuvant setting and targeted sequencing in the advanced stage, has deepened our understanding of disease biology and aided in identifying molecular markers associated with treatment benefit. Finally, the introduction of new drug classes such as antibody-drug conjugates, and the incorporation in the (neo)adjuvant setting of therapies previously investigated in the advanced stage, like immunotherapy and CDK4-6 inhibitors, poses new challenges in treatment sequencing.