Prediction of Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer by Subtype Using Tumor-infiltrating Lymphocytes

Abstract

Recent interest has focused on the significance of tumor-infiltrating lymphocytes (TILs) on the efficacies and outcomes of the treatment in breast cancer (BC). Based on the recent international recommendation to standardize the evaluation method, the clinical validity and utility of TILs in patients who underwent neoadjuvant chemotherapy (NAC) were investigated in the present study. TILs were evaluated in 177 patients with BC treated with NAC and subsequent curative surgery. The correlation between TILs evaluated according to the standard method and prognosis, including the efficacy of NAC, was investigated retrospectively. In the high-TIL group (n=96) compared to the low-TIL group (n=81), triple-negative breast cancer (TNBC) (p<0.001) and human epidermal growth factor receptor 2-enriched breast cancer (HER2BC) (p=0.040) were significantly more frequent, and the pathological complete response (pCR) rate was significantly higher (p=0.003). Among patients with TNBC and those with HER2BC, the pCR rate was significantly higher in the high-TIL group than in the low-TIL group (p=0.013 and p=0.014, respectively). Multivariable analysis also showed that high-TIL status was an independent factor predicting favorable prognosis (hazard ratio(HR)=0.24, p=0.023 and HR=0.13, p=0.036). Biopsy specimens from local recurrence after successful NAC frequently showed TILs decreased. TILs may be a biomarker for predicting treatment response to NAC in patients with TNBC and HER2BC. A decrease in TILs may also be associated with tumor recurrence.