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 their association with outcome and benefit of intensified platinum-based chemotherapy.
Patients in this study participated in a randomized controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracycline-based chemotherapy carried out between 1993-1999 in stage III BC. Stromal TILs were scored according to International guidelines in these HER2-negative tumours. BRCA-profiles were determined using array-based Comparative Genomic Hybridization (aCGH) data.
TIL levels were evaluated in 248 stage III breast tumours. High TILs are associated with TNBC. Tumours were classified as non-BRCA-like (n = 167), BRCA1-like (n = 30), BRCA2-like (n = 39) or BRCA1/2-like (n = 12). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% vs 10%, respectively, p < 0.01). TIL levels in BRCA1-like tumours were higher compared to BRCA2-like (median TILs of 20% vs 10%, respectively, p < 0.001) and non-BRCA-like tumours (median TILs of 10%, p < 0.001). These correlations remained significant within the ER-positive subgroup. Within TNBC, TIL levels were not higher in BRCA-like compared to non-BRCA-like tumours (median TILs of 30% vs 25%, respectively, p = 0.96). In this stage III BC cohort, high TIL level was associated with favourable outcome regarding recurrence-free and overall survival (TILs per 10% increment, HR 0.82, 95% CI 0.71-0.94, p = 0.01, respectively HR 0.80, 95% CI 0.68-0.94, p = 0.01). There was no significant interaction between TIL levels and benefit of intensified platinum-based chemotherapy.
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 non-BRCA-like tumours, but this was not seen within the TNBC subgroup. When adjusted for clinical characteristics, TIL levels were significantly associated with a more favourable outcome in stage III BC patients.
The authors.
Dutch Cancer Society.
A. Cimino-Mathews: Research grant / Funding (self): BMS. S.C. Linn: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Cergentis; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Adienne; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Genentch; Research grant / Funding (institution): Tesaro. M. Kok: Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.