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 A Koop, Zsuzsanna Varga, Carolien H M van Deurzen, Antien L Mooyaart, Alicia Córdoba, Emma J Groen, Joost Bart, Stefan M Willems, Vasiliki 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

Research output: Contribution to journalArticleAcademicpeer-review

2 Downloads (Pure)

Abstract

PURPOSE: Triple-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.

METHODS: We 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.

RESULTS: sTILs 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 (χ2 = 46.7, P < .001).

CONCLUSION: Chemotherapy-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 : official journal of the American Society of Clinical Oncology
Volume40
Issue number21
Early online date30 Mar 2022
DOIs
Publication statusPublished - 20 Jul 2022

Keywords

  • Adult
  • Biomarkers, Tumor
  • Chemotherapy, Adjuvant
  • Humans
  • Lymphocytes, Tumor-Infiltrating
  • Neoadjuvant Therapy
  • Prognosis
  • Prospective Studies
  • Triple Negative Breast Neoplasms/drug therapy

Fingerprint

Dive into the research topics of 'Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy'. Together they form a unique fingerprint.

Cite this