Five Years that Changed Breast Cancer: Advances in Prevention, Diagnosis, and Treatment (2021–2026), and the Rise of Artificial Intelligence in Oncology

Abstract Fifty years ago, five-year survival for breast cancer was 74.8%; today it is 91% overall and exceeds 99% for localized disease, and mortality has fallen 44% since 1989. The last five years accelerated this trajectory across every domain. Prevention moved toward risk-adapted strategies, validated by the WISDOM trial, while polygenic scores and population genetics refined who should be screened and how intensively. Diagnosis sharpened with tomosynthesis, abbreviated MRI, and contrast-enhanced mammography, and circulating tumor DNA began to anticipate recurrence more than a year in advance. Surgery and radiotherapy embraced de-escalation — from sentinel-node validation to the omission of axillary surgery (SOUND) and of radiotherapy itself in low-risk disease (PRIME II, LUMINA) — while hypofractionation compressed treatment into a single week (FAST-Forward). Systemic therapy delivered antibody–drug conjugates that created the HER2-low entity, adjuvant CDK4/6 inhibitors, immunotherapy with proven overall survival in triple-negative disease, PARP inhibition for BRCA carriers, and new endocrine options. Underpinning all of it, genetic and molecular studies turned treatment into a series of biomarker-driven decisions, and artificial intelligence moved from promise to practice in risk prediction, image interpretation, pathology, and response forecasting. This review connects these advances, draws on five decades of perspective, and looks at what comes next.