Tumour-infiltrating lymphocytes (TILs) and BRCA-like status in stage III breast cancer patients randomised to adjuvant intensified platinum-based chemotherapy versus conventional chemotherapy

Leonora de Boo, Ashley Cimino-Mathews, Yoni Lubeck, Antonios Daletzakis, Mark Opdam, Joyce Sanders, Erik Hooijberg, Annelot van Rossum, Zuzana Loncova, Dietmar Rieder, Zlatko Trajanoski, Marieke Vollebergh, Marcelo Sobral-Leite, Koen van de Vijver, Annegien Broeks, Rianne van der Wiel, Harm van Tinteren, Sabine Linn, Hugo Mark Horlings, Marleen Kok

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: The prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC in the context of BRCA1/2-like phenotypes and association with outcome and benefit of intensified platinum-based chemotherapy. Patients and methods: Patients participated in a randomised controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracycline-based chemotherapy carried out between 1993 and 1999 in stage III BC. Stromal TILs were scored according to International guidelines in these human epidermal growth factor receptor 2 (HER2)-negative tumours. BRCA-profiles were determined using Comparative Genomic Hybridization. Results: TIL levels were evaluated in 248 BCs. High TILs were associated with Triple Negative BC (TNBC). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% versus 10%, p < 0.01). TIL levels in BRCA1-like tumours were higher compared to BRCA2-like tumours (median TILs of 20% versus 10%, p < 0.001). These correlations remained significant within the oestrogen (ER)-positive subgroup, however not within the TNBC subgroup. In this stage III BC cohort, high TIL level was associated with favourable outcome (TILs per 10% increment, recurrence-free survival (RFS): multivariate hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71–0.94, p = 0.01; overall survival (OS): multivariate HR 0.80, 95% CI 0.68–0.94, p = 0.01). There was no significant interaction between TILs and benefit of intensified platinum-based chemotherapy. Conclusion: In this high-risk breast cancer cohort, high TILs were associated with TNBC and BRCA1-like status. Within the ER-positive subgroup, TIL levels were higher in BRCA1-like compared to BRCA2-like tumours. When adjusted for clinical characteristics, TILs were significantly associated with a more favourable outcome in stage III BC patients.

Original languageEnglish (US)
Pages (from-to)240-250
Number of pages11
JournalEuropean Journal of Cancer
Volume127
DOIs
StatePublished - Mar 2020

Keywords

  • BRCA1 protein/genetics
  • BRCA2 protein/genetics
  • Breast cancer
  • Carboplatin
  • Homologous recombination deficiency
  • Triple-negative breast neoplasms
  • Tumour-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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