The Effect of Definitive Surgery Timing on The Survival of Breast Cancer Patients : A Systematic Review
Keywords:
Breast cancer, surgical delay, neoadjuvant chemotherapy, survivalAbstract
Introduction: The COVID-19 pandemic necessitated surgical triage, raising urgent questions about how delays in definitive surgery affect breast cancer survival. Existing guidelines lack consensus on acceptable delay thresholds.
Methods: A systematic screening of the literature was performed to identify studies examining the effect of definitive surgery timing on survival in breast cancer patients. Key timing variables included the interval from neoadjuvant chemotherapy (NAC) completion to surgery, diagnosis to surgery, and surgery to adjuvant chemotherapy. Primary outcomes were overall survival (OS) and disease-free survival (DFS).
Results: Pooled meta-analyses demonstrate that delaying surgery beyond 8 weeks after NAC completion significantly worsens OS (OR 0.47, 95% CI 0.34–0.65 for surgery ≤8 weeks) (3,12). A dose-response effect shows a 4-6% increased hazard of death per month of delay (1,23). Pathological response is the critical moderator: delays beyond 9 weeks harm survival exclusively in patients with residual disease (RCB II/III; EFS HR 2.04, p=0.001) but not in those with pathological complete response (7). For upfront surgery, a 12-week delay is associated with an OS HR of 1.46 (95% CI 1.28–1.65) (2). For adjuvant chemotherapy, a 4-week delay increases mortality risk by 6% (HR 1.06, 95% CI 1.02–1.10) (9). HER2-positive patients tolerate delays due to high pCR rates (8), whereas poor NAC responders and TNBC patients require surgery within 4 weeks (6,20).
Discussion: The apparent contradiction between retrospective harm signals and RCT equivalence is resolved by the residual disease framework. Neoadjuvant and adjuvant chemotherapy produce equivalent survival in controlled trials, but indefinite surgical deferral in real-world practice carries oncological cost, particularly in chemo-refractory subtypes.
Conclusion: Surgery should not be delayed beyond 8 weeks after NAC, with a shorter 4-week window preferred for patients with residual disease, TNBC, or poor response. Adjuvant chemotherapy should commence within 8 weeks post-surgery.
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