Tumor-infiltrating lymphocytes in patients with stage i triple-negative breast cancer untreated with chemotherapy

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3 Ottobre 2024
Geurts VCM, Balduzzi S, Steenbruggen TG, et al.

Tumor-infiltrating lymphocytes in patients with stage i triple-negative breast cancer untreated with chemotherapy

JAMA Oncol 2024;10(8):1077-1086
Simonpietro Marrocco Ottobre 2024

Messaggi chiave

  • È stato condotto uno studio di coorte volto a esaminare l’associazione tra densità dei linfociti infiltranti lo stroma tumorale (sTIL) ed esiti di sopravvivenza in pazienti con carcinoma mammario triplo negativo (TNBC) in stadio I non sottoposte a chemioterapia (neo)adiuvante. L’endpoint primario era la sopravvivenza specifica per BC (BCSS) a 5, 10 e 15 anni in funzione di valori soglia predefiniti – 30, 50 e 75% – dei livelli di sTIL.
  • L’analisi ha incluso un totale di 1041 pazienti con diagnosi di TNBC in stadio I ricevuta nel decennio 2005-2015. I livelli di sTIL erano <30, ≥30, ≥50 e ≥75% nel 74,4, 25,6, 19,5 e 13,5% delle pazienti, rispettivamente. Nella coorte complessiva, livelli di sTIL pari almeno al 30% sono risultati associati a un miglioramento della BCSS rispetto a livelli <30% (96 e 87%, rispettivamente; hazard ratio [HR], 0,45; IC 95%, 0,26-0,77). Le pazienti con tumori pT1C che presentavano sTIL ≥50% hanno ottenuto esiti migliori rispetto alle donne con sTIL <50% (HR, 0,27; IC 95%, 0,10-0,74), con una BCSS a 10 anni del 95% (98% in presenza di sTIL ≥75%).
  • Lo studio evidenzia come pazienti con TNBC in stadio I non sottoposte a chemioterapia e con livelli elevati di sTIL godano di una prognosi favorevole, con eccellenti esiti di BCSS a 10 anni. Tali risultati supportano ulteriormente il ruolo dei TIL stromali come biomarcatori di fondamentale importanza nel contesto di studi prospettici futuri volti a individuare strategie di ottimizzazione delle cure per questa popolazione.

Abstract

Importance

  • The absolute benefit of chemotherapy for all patients with stage I triple-negative breast cancer (TNBC) is unclear, and biomarkers are not currently available for selecting patients with an excellent outcome for whom neoadjuvant or adjuvant chemotherapy may have negligible benefit.
  • High levels of stromal tumor-infiltrating lymphocytes (sTILs) are associated with favorable survival in TNBC, but data solely in stage I TNBC are lacking.

Objective

  • To examine the outcomes of patients of all ages with stage I TNBC solely and who received neither neoadjuvant nor adjuvant chemotherapy, according to centrally reviewed sTIL levels at prespecified cutoffs.

Design, setting, and participants

  • This cohort study used the Netherlands Cancer Registry to identify patients diagnosed with stage I TNBC between January 1, 2005, and December 31, 2015, who were not treated with chemotherapy.
  • Only patients who did not receive neoadjuvant and/or adjuvant chemotherapy were selected.
  • The clinical data were matched with their corresponding pathology data provided by the Dutch Pathology Registry.
  • Data analysis was performed between February and October 2023.

Main outcomes and measures

  • The primary end point was breast cancer-specific survival (BCSS) at 5, 10, and 15 years for the prespecified sTIL level cutoffs of 30%, 50%, and 75%.
  • Hematoxylin and eosin-stained slides were used for central review of histologic subtype, grade, and lymphovascular invasion.
  • The International Immuno-Oncology Biomarker Working Group guidelines were used to score the sTIL levels; these levels were determined for 1041 patients.

Results

  • Of a total of 4511 females with stage I TNBC, patients who were not treated with chemotherapy were selected and tissue blocks requested; sTILs were scored in 1041 patients (mean [SD] age at diagnosis, 64.4 [11.1] years, median follow-up 11.4 [95% CI, 10.9-11.9] years) who were included in the analyses.
  • Most tumors (952 [91.5%]) were invasive carcinomas of nonspecial histologic subtype.
  • Most patients (548 [52.6%]) had pT1cN0 tumors.
  • Median (range) sTIL level was 5% (1%-99%).
  • A total of 775 patients (74.4%) had sTIL levels below 30%, 266 (25.6%) had 30% or greater, 203 (19.5%) had 50% or greater, and 141 (13.5%) had 75% or greater.
  • Patients with pT1abN0 tumors had a more favorable outcome vs patients with pT1cN0 tumors, with a 10-year BCSS of 92% (95% CI, 89%-94%) vs 86% (95% CI, 82%-89%).
  • In the overall cohort, sTIL levels of at least 30% were associated with better BCSS compared with sTIL levels less than 30% (96% and 87%, respectively; hazard ratio [HR], 0.45; 95% CI, 0.26-0.77).
  • High sTIL levels of 50% or greater were associated with a better outcome than low sTIL levels of less than 50% (HR, 0.27; 95% CI, 0.10-0.74) in patients with pT1C tumors, with a 10-year BCSS of 95% increasing to 98% with sTIL levels of 75% or greater.

Conclusions and relevance

  • Results of this study showed that patients with stage I TNBC and high level of sTILs who did not receive neoadjuvant or adjuvant chemotherapy had excellent 10-year BCSS.
  • The findings further support the role of sTILs as integral biomarkers in prospective clinical trials of therapy optimization for this patient population.
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