Tumor-infiltrating lymphocytes refine outcomes in triple-negative breast cancer treated with anthracycline-free neoadjuvant chemotherapy.

BACKGROUND:Stromal tumor-infiltrating lymphocytes (sTILs) are associated with pathologic complete response (pCR) and long-term outcomes for triple-negative breast cancer (TNBC) in setting of anthracycline-based chemotherapy. Impact of sTILs on refining outcomes beyond prognostic information provided by pCR in anthracycline-free neoadjuvant chemotherapy (NAC) is not known. PATIENTS & METHODS:This is pooled analysis of two studies where patients with stage I(T>1cm)-III TNBC received carboplatin(AUC 6) plus docetaxel(75mg/m2) (CbD) NAC. sTILs were evaluated centrally on pre-treatment H&E slides using standard criteria. Cox regression analysis was used to examine effect on event-free survival (EFS) and overall survival (OS). RESULTS:Among 474 patients, 44% had node-positive disease. Median sTILs were 5% (range 1%-95%), and 32% of patients had ≥30% sTILs. pCR rate was 51%. On multivariable analysis, T stage (OR=2.08,p=0.007), nodal status (OR=1.64,p=0.035), and sTILs (OR=1.10,p=0.011) were associated with pCR. On multivariate analysis, nodal status (HR=0.46,p=0.008), pCR(HR=0.20,p<0.001), and sTILs(HR=0.95,p=0.049) were associated with OS. At 30% cut-point, sTILs stratified outcomes in stage III disease, 5-year OS 86% vs 57% in ≥30% vs <30% sTILs (HR=0.29,p=0.014), and numeric trend in stage II, 5-year OS 93% vs 89% in ≥30% vs <30% sTILs (HR=0.55,p=0.179). Among stage II-III patients with pCR, EFS was better in those with ≥30% sTILs (HR=0.16,p=0.047). CONCLUSIONS:sTILs density was independent predictor of OS beyond clinicopathologic features and pathologic response in TNBC patients treated with anthracycline-free CbD chemotherapy. Notably, sTILs density stratified outcomes beyond TNM stage and pathologic response. These findings highlight role of sTILs in patient selection/stratification for neo/adjuvant escalation and de-escalation strategies.