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

Published:January 16, 2020DOI:https://doi.org/10.1016/j.ejca.2019.12.003

      Highlights

      • High TILs are significantly associated with TNBC and BRCA1-like breast tumours.
      • In TNBC, TIL levels are similar in BRCA-like versus non-BRCA-like tumours.
      • In ER-positive BCs, BRCA1-like tumours harbour more TILs compared to BRCA2-like tumours.
      • In stage III BC, high TILs are associated with a favourable outcome.
      • TILs are not associated with benefit of intensified platinum-based chemotherapy in this cohort.

      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.

      Keywords

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