Stromal tumor infiltrating lymphocytes and TNBC-DX provide complementary prognostic information in triple-negative breast cancer

Stecklein S.R.; Martín M.; Villacampa G.; Del Monte-Millan M.; Yoder R.; Pathak H.; Cobo S.; Brasó-Maristany F.; Álvarez E.L.; Echavarría I.; Bueno-Muiño C.; Jerez Y.; Cebollero M.; Bueno O.; García-Saenz J.Á.; Moreno F.; Gómez H.L.; Massarrah T.; Herrero B.; Paré L.; Marín-Aguilera M.; Buckingham W.; López-Tarruella S.; Villagrasa P.; Godwin A.K.; Salgado R.; Prat A.; Sharma P. · Journal of the National Cancer Institute (2026) · DOI: 10.1093/jnci/djaf162

Resumen

Patients with triple-negative breast cancer (TNBC) who achieve pathologic complete response (pCR) to neoadjuvant systemic therapy have favorable survival, while those with residual disease have high recurrence risk. Stromal tumor infiltrating lymphocytes (sTILs) and TNBC-DX both predict pCR in TNBC. Whether these 2 biomarkers provide complementary information has not been tested. We evaluated sTILs and TNBC-DX in TNBC patients treated with docetaxel-carboplatin (TCb) on the MMJ-CAR-2014-01 study (NCT01560663) or TCb plus pembrolizumab (TCb+Pem) on the NeoPACT trial (NCT03639948). sTILs and TNBC-DX independently predicted pCR in patients treated with TCb+Pem. Patients with sTILs ≥ 30% and a TNBC-DX pCR-high genomic score achieved a pCR rate of 91.3% with TCb+Pem. An integrated classification incorporating sTILs and TNBC-DX identified approximately 40% of the NeoPACT cohort with a pCR rate exceeding 85%. The integrated classification was prognostic for event-free survival in patients treated with TCb+Pem. Integrating sTILs and TNBC-DX may facilitate chemoimmunotherapy escalation and de-escalation trials.