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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Article info
Publication history
Published online: January 16, 2020
Accepted:
December 5,
2019
Received in revised form:
November 26,
2019
Received:
August 30,
2019
Identification
Copyright
© 2019 Elsevier Ltd. All rights reserved.
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- Tumour infiltrating lymphocytes and correlation with response to intensified platinum-based chemotherapy in BRCA-like tumoursEuropean Journal of CancerVol. 127
