Prognostic and predictive value of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancers (TNBC) treated with neoadjuvant chemotherapy (NAC)

Background

Recent clinical studies have evaluated TILs in TNBC patients(pts) with different methodological approaches. The aim is to analyse the predictive and prognostic value of TIL following the recommendations for TILs Evaluations in Breast Cancer(BC) by an International TIL Working Group.

Methods

Using our BC database with 756 pts, we identified 164 TNBC treated with NAC between 1998-2015. Evaluation of TILs was following a standardized methodology for visual assessment on hematoxylin-eosin sections and TILs were quantitated in deciles. We categorized lymphocyte-predominant BC (LPBC) cutoff according to a receiver operating characteristic (ROC) curve. The primary endpoint was predictive value of TILs to NAC and secondary endpoint was disease-free survival (DFS). Kaplan-Meier curves were used to summarize DFS, and curves were compared with a log-rank test. Univariate and multivariate Cox models were used to generate hazard ratios (HR) for determining associations between variables and DFS.

Results

We categorized LPBC as the involving > 40% TIL stroma. Pts were divided in subgroups:58 pts (35.4%) with LPBC and 106 pts (64.6%) non-LPBC. Main pts' characteristics are listed in Table 1. We identify different pathological complete response (pCR) to anthracycline and taxane-based NAC; LPBC 88% pCR vs non-LPBC 9% pCR, p = 0.001. At a median follow-up of 78 months, LPBC was associated with better DFS; the 3-year Kaplan-Meier estimates for DFS were 2 % and 30% in LPBC and non-LPBC, respectively p = 0.01. Univariate and multivariate analysis confirmed TIL to be an independent prognostic marker of DFS.

Patient's characteristics

Conclusions

TIL evaluation in TNBC pts could be included in the standard histopathological practise to identify two subgroups; LPBC with high pCR response to NAC and non-LPBC with worse prognosis. While our findings may not change current NAC options, it is a clinically relevant finding as TIL could be useful as an adjustment factor in future studies.

Clinical trial identification

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Legal entity responsible for the study

N/A

Funding

Fundación Colegio de Médico de Valencia

Disclosure

All authors have declared no conflicts of interest.