Abstract GS2-03: Pathological complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and mortality, stratified by breast cancer subtypes and adjuvant chemotherapy usage: Individual patient-level meta-analyses of over 27,000 patients
Authors: Spring LM , Fell G , Arfe A , Trippa L , Greenup R , Reynolds K , Smith BL , Moy B , Isakoff SJ , Parmigiani G , Bardia A 
Published: May 2019

Abstract
Background: While the prognostic significance of pathological complete response (pCR) after neoadjuvant chemotherapy is relatively well established, the impact of adjuvant therapy in modulating relationship between pCR and long term outcomes is less clear. The primary objective of this study was to conduct a systematic review of published neoadjuvant chemotherapy studies to comprehensively evaluate the association between pCR with subsequent breast cancer recurrence and mortality, stratified by breast cancer subtypes and adjuvant chemotherapy usage.
Methods: Based on PRISMA guidelines, a search of PubMed from inception until September 2016 was performed to identify eligible studies. Inclusion criteria were clinical trials or studies featuring neoadjuvant chemotherapy that reported pCR results as well as recurrence and/or survival. Hazard Ratios (HRs) and 95% probability intervals (PI) were estimated for endpoints using hierarchical models. We obtained the individual patient-level data for statistical analysis using plot digitizer software. Hazard ratios (HRs), with 95% PIs, measuring the association between pCR and OS or recurrence, were estimated using Bayesian piecewise-exponential proportional hazards hierarchical models including pCR as a predictor. Random effects model was utilized to account for between-study variability in baseline hazards and the variability of the pCR effect between studies. P-value of 0.05 was considered statistically significant.
Results: A total of 3,209 citations with associated abstracts were reviewed, and 27,895 patients from 52 studies met inclusion criteria. Attainment of pCR, as compared to absence of pCR, was associated with significantly reduced disease recurrence overall (HR 0.31, 95% PI: 0.24-0.39), and in triple negative (HR 0.18, 95% PI: 0.10-0.31), human epidermal growth factor 2-positive (HER2+) (HR 0.32, 95% PI: 0.21-0.47), and trended towards significance for HR+ breast cancer (HR 0.15, 95% PI: 0.02-1.10). Similarly, pCR after neoadjuvant chemotherapy was also associated with reduced mortality overall (HR 0.22, 95% PI: 0.15-0.30), and among all three major disease subtypes. The association of pCR with reduced recurrence was similar among studies where patients received subsequent adjuvant chemotherapy (HR 0.34, 95% PI: 0.18-0.61) and those without adjuvant chemotherapy (95% HR 0.36, PI: 0.27-0.54). The association between magnitude of pCR change and corresponding change in survival will be presented at the meeting.
Conclusion: Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved disease recurrence and survival, particularly for triple negative and HER2+ breast cancer. The similar outcomes with/without adjuvant chemotherapy in patients who attain pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be abbreviated in certain circumstances, and highlights the need for further research to evaluate clinical utility of escalation/de-escalation strategies in the adjuvant setting based on neoadjuvant response for patients with localized breast cancer.
Citation Format: Spring LM, Fell G, Arfe A, Trippa L, Greenup R, Reynolds K, Smith BL, Moy B, Isakoff SJ, Parmigiani G, Bardia A. Pathological complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and mortality, stratified by breast cancer subtypes and adjuvant chemotherapy usage: Individual patient-level meta-analyses of over 27,000 patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS2-03.