Prognostic utility of tumor-infiltrating lymphocytes in residual tumor after neoadjuvant chemotherapy with trastuzumab for HER2-positive breast cancer

Sasagu Kurozumi,Hiroshi Matsumoto,Takaaki Fujii,Ken Shirabe,Jun Horiguchi,Kenichi Inoue,Masafumi Kurosumi,Tetsunari Oyama

doi:10.1038/s41598-018-38272-1

Abstract

Predictive utility of tumor-infiltrating lymphocytes (TILs) in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy (NAC) with concurrent trastuzumab remains unclear. We examined TILs grades of pretreatment cancer tissue specimens and residual tumors after NAC with trastuzumab and determined the predictive utility of the TILs grade in pathological complete response (pCR) and the prognostic power of TILs in HER2-positive breast cancer. This cohort study included 128 HER2-positive breast cancer who received NAC with trastuzumab. TILs grading of the tumor stroma in pretreatment biopsy specimens and residual tumors after NAC with trastuzumab was categorized as low, intermediate, and high based on the criteria of the International Working Group. In current study, the pCR rate was 64.8%, and the Relapse-free survival (RFS) was significantly worse in the non-pCR group than in the pCR group. The pCR rate correlated with the TILs grade in pretreatment tumors. In 45 non-pCR patients, TILs grade was higher in the residual tumors than in the pretreatment tumors. The RFS was significantly better in residual tumors with high TILs grade than those with low TILs grade (p = 0.033). In conclusion, assessment of the TILs grade in residual tumors after NAC with trastuzumab might be necessary to determine patients with good prognosis among those who do not achieve pCR.

Highlights

A variety of clinical trials on neoadjuvant chemotherapy (NAC) for breast cancer demonstrated its utility in both early-stage and advanced breast cancer
The current study analyzing the role of tumor-infiltrating lymphocytes (TILs) grade in HER2-positive breast cancer revealed that a high TILs grade in the primary tumor was associated with a significantly higher pathological complete response (pCR) rate
The TILs grade was increased after treatment compared with the pretreatment TILs status in 20.0% of the patients who did not achieve pCR after preoperative treatment

Summary

Introduction

A variety of clinical trials on neoadjuvant chemotherapy (NAC) for breast cancer demonstrated its utility in both early-stage and advanced breast cancer. Recent clinical trials on new drugs for breast cancer evaluated their efficacy by assessing preoperative drug therapy with pCR as an endpoint[3]. Many retrospective studies suggested the potential utility of TILs expression in breast cancer as a prognostic factor and a predictor of the efficacy of drug therapy[5,6,7,8,9,10]. Clinical trials on adjuvant chemotherapy for breast cancer, the results of the Breast International Group (BIG) 2–98 trial[11] suggested an association between TILs expression and the efficacy of anthracyclines in HER2-positive breast cancer. The drug effect of TILs in preoperative chemotherapy combined with trastuzumab and its utility as a prognostic factor in HER2-positive breast cancer remain controversial. We assessed the association of TILs expression with pCR and prognosis following combination treatment with NAC and trastuzumab

Methods

Results

Conclusion