TILs have been proposed as a prognostic biomarker in many tumor types both in the adjuvant and neoadjuvant setting. In TNBC, TILs are present at the highest level and have been demonstrated to be associated with better prognosis. TNBC is a highly diverse group of cancers and subtyping is necessary to better identify patient-tailored therapies. Cluster analysis by gene expression identified 6 TNBC subtypes among which the so called “luminal androgen receptor subtype”.
We retrospectively collected 160 early stage TNBC consecutively treated at our Institution from 2006 to 2015. Data were obtained for clinico-pathological patients' characteristics. On IHC archive slides we analyzed stromal TILs scored as a continuous variable and androgen receptor's (AR) percentage and intensity of expression. We performed Cox analyses for DFS and for OS, and we used chi-square and Fisher test to evaluate the correlation between TILs, AR and other clinical variables. To define high vs low TILs, an internal dataset cut-off of 10% was considered.
150 patients were eligible for IHC analyses of TILs and AR. With a median follow-up of 6.5 years, 41 local and/or distant relapse events were observed and 28 patients died of disease. Interestingly, TILs were found to be significantly associated with nodal status (N0 vs N1-3), grading (G2 vs G3) and Ki-67 (<20% vs ≥ 20%) (p = 0.007, p = 0.055 and p = 0.002, respectively). AR was also significantly associated with proliferation, specifically AR-positive cases presented mostly with a Ki-67<20% (p = 0.008). Probably due to the paucity of events, no statistically significant association of TILs and AR with either DFS or OS was observed.
TILs are a promising prognostic marker, but still prospective validation is needed to integrate them into clinical practice. Among TNBC, the identification of AR-expressing luminal subtype might provide a targeted therapy chance for a low proliferation TNBC subtype. Larger prospective trials are likely to validate TILs prognostic role and to explore the universe of TNBC subtypes targeted therapies opportunities.
Istituto Clinico Humanitas.
Has not received any funding.
All authors have declared no conflicts of interest.