Abstract

Background: Adjuvant systemic therapy has fundamentally altered the natural history of early breast cancer. Beginning with Bonadonna’s CMF program, the curative principle of micrometastatic eradication became clinically proven, and subsequent EBCTCG meta-analyses quantified durable reductions in recurrence and mortality with polychemotherapy.^1–6

Methods: Evidence-based narrative review of biological foundations (tumor kinetics and resistance), landmark randomized trials, meta-analyses, and contemporary subtype-driven strategies integrating chemotherapy, endocrine therapy, and modern biologic/targeted agents.

Results: Anthracycline and taxane-based regimens improved outcomes over earlier approaches, with additional gains from dose-dense scheduling (validated by randomized trials). HER2-directed therapy (trastuzumab ± pertuzumab) produced major reductions in recurrence; response-adapted escalation with antibody–drug conjugates further improved outcomes in residual disease. In HR-positive disease, endocrine therapy is foundational and long-horizon, while genomic assays refine chemotherapy selection. In TNBC, post-neoadjuvant capecitabine and perioperative immunotherapy improve event-free outcomes. In selected high-risk HR+/HER2− disease, CDK4/6 inhibition improves invasive disease-free survival; and in germline BRCA1/2-mutated high-risk HER2− disease, adjuvant PARP inhibition improves invasive DFS and overall survival.^{4–12,14–30}

Conclusions: Modern adjuvant care is biology-driven and risk-adapted. Integrating subtype, nodal burden, genomic risk, and response to preoperative therapy maximizes cure while minimizing toxicity and overtreatment. Future directions include ctDNA-based minimal residual disease (MRD) strategies and adaptive escalation/de-escalation trials.^31–36

 

Keywords

systemic therapy, contemporary,cancer mortality