Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy

Vincent M.T. de Jong, Yuwei Wang, Natalie D. ter Hoeve, Mark Opdam, Nikolas Stathonikos, Katarzyna Jóźwiak, Michael Hauptmann, Sten Cornelissen, Willem Vreuls, Efraim H. Rosenberg, Esther Koop, Zsuzsanna Varga, Carolien H.M. van Deurzen, Antien L. Mooyaart, Alicia Cordoba, Emilie J. Groen, Joost Bart, Stefan M. Willems, Vasliki Zolota, Jelle WesselingAnna Sapino, Ewa Chmielik, Ales Ryska, Annegien Broeks, Adri C. Voogd, Sherene Loi, Stefan Michiels, Gabe S. Sonke, Elsken Van Der Wall, Sabine Siesling, Paul J. van Diest, Marjanka K. Schmidt, Marleen Kok, Gwen M.H.E. Dackus, Roberto Salgado, Sabine C. Linn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

PURPOSETriple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young (< 40 years), and chemotherapy-naïve, and thus can be used for chemotherapy de-escalation strategies, is unknown.METHODSWe selected all patients with N0 TNBC diagnosed between 1989 and 2000 from a Dutch population-based registry. Patients were age < 40 years at diagnosis and had not received (neo)adjuvant systemic therapy, as was standard practice at the time. Formalin-fixed paraffin-embedded blocks were retrieved (PALGA: Dutch Pathology Registry), and a pathology review including sTILs was performed. Patients were categorized according to sTILs (< 30%, 30%-75%, and ≥ 75%). Multivariable Cox regression was performed for overall survival, with or without sTILs as a covariate. Cumulative incidence of distant metastasis or death was analyzed in a competing risk model, with second primary tumors as competing risk.RESULTSsTILs were scored for 441 patients. High sTILs (≥ 75%; 21%) translated into an excellent prognosis with a 15-year cumulative incidence of a distant metastasis or death of only 2.1% (95% CI, 0 to 5.0), whereas low sTILs (< 30%; 52%) had an unfavorable prognosis with a 15-year cumulative incidence of a distant metastasis or death of 38.4% (32.1 to 44.6). In addition, every 10% increment of sTILs decreased the risk of death by 19% (adjusted hazard ratio: 0.81; 95% CI, 0.76 to 0.87), which are an independent predictor adding prognostic information to standard clinicopathologic variables (χ= 46.7, P <.001).CONCLUSIONChemotherapy-naïve, young patients with N0 TNBC with high sTILs (≥ 75%) have an excellent long-term prognosis. Therefore, sTILs should be considered for prospective clinical trials investigating (neo)adjuvant chemotherapy de-escalation strategies.

Original languageEnglish
Pages (from-to)2361-2374
Number of pages14
JournalJournal of clinical oncology
Volume40
Issue number21
Early online date30 Mar 2022
DOIs
Publication statusPublished - 20 Jul 2022

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