Data from Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy

Miguel Martín,Rachel Yoder,Roberto Salgado,María Del Monte-Millán,Enrique L Álvarez,Isabel Echavarría,Joshua M Staley,Anne P O'Dea,Lauren E Nye,Shane R Stecklein,Coralia Bueno,Yolanda Jerez,María Cebollero,Oscar Bueno,José Ángel García Saenz,Fernando Moreno,Uriel Bohn,Henry Gómez,Tatiana Massarrah,Qamar J Khan,Andrew K Godwin,Sara López-Tarruella,Priyanka Sharma

doi:10.1158/1078-0432.c.7234911

Abstract

<div>AbstractPurpose:Stromal tumor-infiltrating lymphocytes (sTIL) are associated with pathologic complete response (pCR) and long-term outcomes for triple-negative breast cancer (TNBC) in the setting of anthracycline-based chemotherapy. The impact of sTILs on refining outcomes beyond prognostic information provided by pCR in anthracycline-free neoadjuvant chemotherapy (NAC) is not known.Experimental Design:This is a pooled analysis of two studies where patients with stage I (T>1 cm)–III TNBC received carboplatin (AUC 6) plus docetaxel (75 mg/m2; CbD) NAC. sTILs were evaluated centrally on pre-treatment hematoxylin and eosin slides using standard criteria. Cox regression analysis was used to examine the effect of variables 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, with 5-year OS 86% versus 57% in ≥30% versus <30% sTILs (HR, 0.29; P = 0.014), and numeric trend in stage II, with 5-year OS 93% versus 89% in ≥30% versus <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 an independent predictor of OS beyond clinicopathologic features and pathologic response in patients with TNBC treated with anthracycline-free CbD chemotherapy. Notably, sTILs density stratified outcomes beyond tumor–node–metastasis (TNM) stage and pathologic response. These findings highlight the role of sTILs in patient selection and stratification for neo/adjuvant escalation and de-escalation strategies.</div>

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