Pathologic Complete Response after Neoadjuvant Chemotherapy and Impact on Breast Cancer Recurrence and Survival: A Comprehensive Meta-analysis

Clin Cancer Res. 2020 Jun 15;26(12):2838-2848. doi: 10.1158/1078-0432.CCR-19-3492. Epub 2020 Feb 11.


Purpose: While various studies have highlighted the prognostic significance of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAT), the impact of additional adjuvant therapy after pCR is not known.

Experimental design: PubMed was searched for studies with NAT for breast cancer and individual patient-level data was extracted for analysis using plot digitizer software. HRs, with 95% probability intervals (PI), measuring the association between pCR and overall survival (OS) or event-free survival (EFS), were estimated using Bayesian piece-wise exponential proportional hazards hierarchical models including pCR as predictor.

Results: Overall, 52 of 3,209 publications met inclusion criteria, totaling 27,895 patients. Patients with a pCR after NAT had significantly better EFS (HR = 0.31; 95% PI, 0.24-0.39), particularly for triple-negative (HR = 0.18; 95% PI, 0.10-0.31) and HER2+ (HR = 0.32; 95% PI, 0.21-0.47) disease. Similarly, pCR after NAT was also associated with improved survival (HR = 0.22; 95% PI, 0.15-0.30). The association of pCR with improved EFS was similar among patients who received subsequent adjuvant chemotherapy (HR = 0.36; 95% PI, 0.19-0.67) and those without adjuvant chemotherapy (HR = 0.36; 95% PI, 0.27-0.54), with no significant difference between the two groups (P = 0.60).

Conclusions: Achieving pCR following NAT is associated with significantly better EFS and OS, particularly for triple-negative and HER2+ breast cancer. The similar outcomes with or without adjuvant chemotherapy in patients who attain pCR likely reflects tumor biology and systemic clearance of micrometastatic disease, highlighting the potential of escalation/deescalation strategies in the adjuvant setting based on neoadjuvant response.See related commentary by Esserman, p. 2771.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bayes Theorem
  • Breast Neoplasms* / drug therapy
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Humans
  • Neoadjuvant Therapy*
  • Neoplasm Recurrence, Local / drug therapy