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

• Published in: Clinical cancer research Vol. 30; no. 10; pp. 2160 - 2169
• Main Authors: Martín, Miguel, Yoder, Rachel, Salgado, Roberto, Del Monte-Millán, María, Álvarez, Enrique L, Echavarría, Isabel, Staley, Joshua M, O'Dea, Anne P, Nye, Lauren E, Stecklein, Shane R, Bueno, Coralia, Jerez, Yolanda, Cebollero, María, Bueno, Oscar, García Saenz, José Ángel, Moreno, Fernando, Bohn, Uriel, Gómez, Henry, Massarrah, Tatiana, Khan, Qamar J, Godwin, Andrew K, López-Tarruella, Sara, Sharma, Priyanka
• Format: Journal Article
• Language: English
• Published: United States 15.05.2024
• Subjects: Adult; Aged; Anthracyclines - administration & dosage; Anthracyclines - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; Docetaxel - administration & dosage; Docetaxel - therapeutic use; Female; Humans; Lymphocytes, Tumor-Infiltrating - immunology; Middle Aged; Neoadjuvant Therapy - methods; Neoplasm Staging; Prognosis; Treatment Outcome; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - mortality; Triple Negative Breast Neoplasms - pathology
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-24-0106

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. 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). 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). 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.