Breast cancer in 2025: navigating new horizons of precision-guided de-escalation

Abstract The years 2024–2025 has marked a period of profound evolution in the management of breast cancer, characterized by the consolidation of established therapies and the emergence of transformative new strategies across all subtypes. The field of locoregional management is undergoing a paradigm shift towards surgical de-escalation, with landmark trials questioning the necessity of long-held axillary procedures. For hormone receptor-positive (HR +) breast cancer, the narrative has shifted from the initial adoption of CDK4/6 inhibitors (CDK4/6i) to refining their use in the adjuvant setting and, critically, defining the complex therapeutic landscape following their progression. The rise of antibody–drug conjugates (ADCs) continues to blur traditional subtype boundaries, particularly with the expansion of trastuzumab deruxtecan into the HER2-low and even “HER2-ultralow” populations. In HER2-positive (HER2 +) breast cancer, ADCs are challenging the long-standing first-line standards, while de-escalation strategies in early-stage disease are gaining robust evidence. For triple-negative breast cancer (TNBC), long-term data has solidified the role of immunotherapy, while molecular subtyping is finally translating into tangible clinical benefits in first-line precision trials. This commentary synthesizes the pivotal data from 2024–2025, exploring the clinical implications and future directions of these advancements.