Ki67 Index Changes and Tumor-Infiltrating Lymphocyte Levels Impact the Prognosis of Triple-Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Chemotherapy.

Yihua Wang,Rui Chen,Man Huang,Shengchun Liu,Beige Zong,Zhenrong Tang,Yu Wang,Yu Yu

doi:10.3389/fonc.2021.668610

Abstract

PurposeThe aim of this study was to assess the prognostic influence of Ki67 index changes in patients with primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), and to evaluate whether the combination of Ki67 index changes and residual disease (RD) tumor-infiltrating lymphocytes (TILs) provides additional prognostic information for this group.Materials and MethodsData from 109 patients with primary TNBC and RD after NAC were analyzed retrospectively. Ki67 changes and RD TIL levels were investigated for associations with recurrence-free survival (RFS) and overall survival (OS) using Kaplan–Meier and Cox analyses.ResultsKi67 index decreased after NAC in 53 patients (48.6%) and high RD TIL levels (≥30%) were observed in 54 patients (49.5%). In multivariate Cox analyses, no Ki67 decrease status and low RD TIL levels were significantly associated with reduced RFS (hazard ratio (HR): 2.038, 95% confidence interval (CI): 1.135–3.658, P = 0.017; HR: 2.493, 95% CI: 1.335–4.653, P = 0.004), and OS (HR: 2.187, 95% CI: 1.173–4.077, P = 0.014; HR: 2.499, 95% CI: 1.285–4.858, P = 0.007), respectively. Notably, low RD TIL levels were significantly associated with reduced RFS (HR: 3.567, 95% CI: 1.475–8.624, P = 0.005) and reduced OS (HR: 3.873, 95% CI: 1.512–9.918, P = 0.005) in only the no Ki67 decrease group. The differences in 3-year RFS and OS between patients with no Ki67 decrease and low or high RD TIL levels were 24.4% vs 79.1% (P = 0.0001) and 33.1% vs 87.5% (P = 0.0001), respectively.ConclusionKi67 index changes and RD TIL levels were associated with the prognosis of patients with primary TNBC with RD after NAC. RD TIL levels had greater prognostic significance in the no Ki67 decrease group.

Highlights

Triple-negative breast cancer (TNBC) is a specific subtype with an aggressive clinical manifestation that accounts for approximately 15–20% of breast cancers
In the no Ki67 decrease group, low residual disease (RD) TIL levels were significantly associated with reduced RFS and OS, with estimated hazard ratios (HRs) values of 3.567 and 3.873, respectively
We found that no Ki67 decrease status and low RD TIL levels after Neoadjuvant chemotherapy (NAC) were significantly associated with worse RFS and OS in patients with TNBC and RD

Summary

Introduction

Triple-negative breast cancer (TNBC) is a specific subtype with an aggressive clinical manifestation that accounts for approximately 15–20% of breast cancers. TNBCs tend be a higher clinical stage and are more prone to recurrence and metastasis than other breast cancer subtypes [1]. Patients with TNBC who achieve pathological complete response (pCR) after NAC have better prognosis than those who do not reach pCR [3, 4]; numerous patients with TNBC have residual disease (RD) after NAC, which is associated with a higher risk of relapse and distant metastasis [5, 6]. Novel prognostic biomarkers that can stratify these patients will be valuable for making individualized treatment decisions and maximizing therapeutic efficacy in specific patient groups

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