Prognostic value of tumor: Infiltrating lymphocytes and androgen receptors correlation in triple negative breast cancer.

Abstract

e12571 Background: Little is known about correlation of tumor infiltrating lymphocytes (TIL) and androgen receptors (AR) and their joint effect on early triple-negative breast cancer (TNBC) prognosis. Analyzes to date evaluated mostly stromal TIL (sTIL) and intratumoral (iTIL), but not separately in central tumor (CT) and invasive margin (IM). Methods: We retrospectively analyzed consecutive sample of 152 early TNBC patients treated at our institution 2009-2012. TIL and AR were assessed using standard FFPE samples, TIL according to International Working Group for Evaluation of TIL recommendation, sTIL and iTIL in CT and IM, and AR by immunohistochemistry. Results: Median age was 58, 84% NOS, median T 2.2cm, 41% N+, 22%, 59% and 19% in stage I, II and III, respectively. Radical mastectomy was performed in 39%, adjuvant chemotherapy in 88% and radiotherapy in 74% of patients. Positive AR defined as ≥1% nuclear-stained cells, were expressed in 31%, and AR≥10% in 26% of patients. Median TIL content was: sTIL 19%, iTIL 5%, TIL in CT 5%, at IM 18%, sTIL in CT (CTs) 5%, iTIL in CT (CTi) 1%, sTIL at IM (IMs) 30%, and iTIL at IM (IMi) 5%. Prevalence of intermediate or high TIL content, defined as ≥10% was: CTs in 48%, CTi in 23%, IMs in 86%, and IMi in 47% of cases. In bivariable analysis all TIL indicators were significantly associated with longer OS, while AR was not. After adjustment for potential confounders using Cox proportional hazard regression, significant predictors of OS were sTIL (p0.007), IM TIL (p0.002), IMs (p0.001), and IMi (p0.030). In all cases higher TIL content was associated with longer OS. Although AR was not significant predictor of OS, it's interactions with TIL IMs and IMi was. There was no significant difference in OS between patients with high IMs and low IMs and AR0, but those with high IMs and AR≥1 had HR0.22 (p0.045) for death compared to patients with low IMs and AR0. Also, no difference for high IMi and low IMi and AR0, but patients with high IMi and AR≥1 had HR0.10 (p0.028) for death compared to patients with low IMi and AR0. Conclusions: Section analysis reveals frequent intermediate to high density and statistically significant prognostic impact of TIL on IM. That directs question towards role of different tumor compartments. Furthermore, combination of high expression of IMs and IMi with AR≥1 appears to be associated with longer OS than in patients with high IMs and IMi but with AR0. The correlations between AR and all TIL studied are extremely small, indicating their independence, but if so, their interaction in impact on OS is particularly interesting.