Effect of neoadjuvant chemotherapy regimen on relapse-free survival among patients with breast cancer achieving a pathologic complete response: an early step in the de-escalation of neoadjuvant chemotherapy

Anna Weiss,Kenneth Hess,Nuhad K. Ibrahim,Alastair M. Thompson,Sami I. Bashour

doi:10.1186/s13058-018-0945-7

Abstract

BackgroundPatients with breast cancer who have a pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) have improved survival. We hypothesize that once pCR has been achieved, there is no difference in subsequent postsurgical recurrence-free survival (RFS), whichever NACT regimen is used.MethodsData from patients with breast cancer who achieved pCR after NACT between 1996 and 2011 were reviewed. RFS was estimated by the Kaplan-Meier method, and differences between groups were assessed using log-rank testing. Cox proportional hazards regression analysis adjusted for age, menopausal status, stage, grade, tumor subtype, and adjuvant endocrine HER2-targeted radiation treatment.ResultsAmong 721 patients who achieved pCR after NACT, 157 (21.8%) were hormone receptor-positive (HR), 310 (43.3%) were HER2-amplified, and 236 (32.7%) were triple-negative; 292 (40.5%) were stage IIA, 153 (21.2%) were stage IIB, 78 (10.8%) were stage IIIA, 66 (9.2%) were stage IIIB, and 132 (18.3%) were stage IIIC. Most patients (367 [50.9%]) had been treated with adriamycin-based chemotherapy plus taxane (A + T), 56 (7.8%) without taxane (A no T), 227 (31.5%) with HER2-targeted therapy, and 71 (9.8%) provider choice. Median follow-up was 7.1 years. Adjuvant chemotherapy was employed in 196 (27%) patients, adjuvant endocrine in 261 (36%), and adjuvant radiation in the majority (559 [77.5%]). There was no statistically significant difference in RFS by NACT group. Adjusted RFS hazard ratios, comparing each treatment with the reference group A + T, were 1.25 (95% CI 0.47–3.35) for A no T, 0.90 (95% CI 0.37–2.20) for HER2-targeted therapy, and 1.28 (95% CI 0.55–2.98) for provider choice.ConclusionsThese data suggest that postsurgical RFS is not significantly influenced by the choice of NACT or cancer subtype among patients achieving pCR.

Highlights

Patients with breast cancer who have a pathologic complete response to neoadjuvant chemotherapy (NACT) have improved survival
For HER2-targeted therapy, and 1.28 for provider choice. These data suggest that postsurgical recurrence-free survival (RFS) is not significantly influenced by the choice of NACT or cancer subtype among patients achieving pathologic complete response (pCR)
Low (RCB I) or no residual disease (RCB 0, defined as pCR) is associated with improved survival compared with more residual disease (RCB II or III), a relationship that holds true across breast cancer subtypes [1,2,3,4]

Summary

Introduction

Patients with breast cancer who have a pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) have improved survival. We hypothesize that once pCR has been achieved, there is no difference in subsequent postsurgical recurrence-free survival (RFS), whichever NACT regimen is used. Neoadjuvant chemotherapy (NACT), originally used to downstage breast cancer, may achieve a pathologic complete response (pCR) in a proportion of patients, with no residual invasive disease in the breast or nodes [1]. Large randomized clinical trials have shown that more recent NACT regimens have provided increased pCR rates [5, 6], and some trials have shown resultant improved survival [1, 7]. The timing of chemotherapy and use of NACT have not historically impacted overall survival (OS) [8,9,10,11,12,13], important therapeutic information may be gained by evaluating tumor response to chemotherapy [14, 15].

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