Tumor infiltrating lymphocytes in patients receiving trastuzumab/pertuzumab-based chemotherapy: A TRYPHAENA substudy

ABSTRACT: Background: It is critical to identify biomarkers for treatment tailoring in HER2-amplified early breast cancer treated with trastuzumab/pertuzumab-based chemotherapy. Patients and methods: Among the 225 patients randomized to trastuzumab/pertuzumab concurrently or sequentially with an anthracycline-containing regimen or concurrently with an anthracycline-free regimen in the Tryphaena trial, we evaluated TILs at baseline in 213 patients of whom 126 with pathological complete response, pCR (ypT0/is ypN0) and 28 with Event Free Survival, EFS events. We computed associations between baseline TILs and either pCR or EFS after adjusting for clinicopathological characteristics using logistic and Cox regression models, respectively. To understand TILs biology, we evaluated associations between baseline TILs and baseline tumor gene expression data (800 gene set by NanoString) in a subset of 173 patients. Results: Among the 213 patients with evaluable TILs at baseline, the median level of TILs was 14% (interquartile range, IQR, 7-32%). After adjusting for clinicopathological characteristics, baseline TILs were not associated with pCR (adjusted odds ratio for every 10% increase in TILs aOR 1.12, 95%CI 0.95-1.31, p=0.17). At a median follow-up of 4.7 years, for every increase in baseline TILs of 10 percentage units there was a 25% reduction in the hazard of the EFS event (adjusted hazard ratio 0.75, 95%CI 0.56-1.00, p=0.05) after adjusting for baseline clinicopathological characteristics and pCR. Genes associated with Epithelial-Mesenchymal Transition (EMT) such as SNAIL1, TWIST1, ZEB1, B7-H3 and NOTCH3 were significantly anti-correlated with TILs. Conclusions: Baseline TILs provide independent prognostic information in patients treated with trastuzumab/pertuzumab-based neoadjuvant chemotherapy. Further validation is needed.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109710 | GEO | 2018/04/01

REPOSITORIES: GEO