Format

Send to

Choose Destination
Clin Cancer Res. 2019 Mar 1;25(5):1535-1545. doi: 10.1158/1078-0432.CCR-18-2365. Epub 2018 Dec 6.

NK Cell Infiltrates and HLA Class I Expression in Primary HER2+ Breast Cancer Predict and Uncouple Pathological Response and Disease-free Survival.

Author information

1
Immunity and Infection Lab, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain. amuntasell@imim.es jalbanell@hospitaldelmar.cat.
2
Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.
3
Department of Pathology, IIS 'Fundación Jiménez Diaz', Madrid, Spain.
4
Department of Medical Oncology, Hospital del Mar-CIBERONC, Barcelona, Spain.
5
Institute for Research in Biomedicine, Barcelona Institute of Science and Technology, Barcelona, Spain.
6
Immunity and Infection Lab, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.
7
Department of Oncology Pathology, Karolinska Institutet, Stockholm, Sweden.
8
Pompeu Fabra University, Barcelona, Spain.
9
Department of Pathology, Hospital del Mar, Barcelona, Spain.
10
Department of Oncology, Hospital Clinico de Valencia-CIBERONC, Valencia, Spain.
11
Universitat de Valencia, Valencia, Spain.
12
Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain. amuntasell@imim.es jalbanell@hospitaldelmar.cat.
#
Contributed equally

Abstract

PURPOSE:

We investigated the value of tumor-infiltrating NK (TI-NK) cells and HLA class I tumor expression as biomarkers of response to neoadjuvant anti-HER2 antibody-based treatment in breast cancer.

EXPERIMENTAL DESIGN:

TI-NK cells and HLA-I were determined by IHC in pretreatment tumor biopsies from two cohorts of patients with HER2-positive breast cancer [discovery cohort (n = 42) and validation cohort (n = 71)]. Tumor-infiltrating lymphocytes (TIL) were scored according to international guidelines. Biomarker association with pathologic complete response (pCR) and disease-free survival (DFS) was adjusted for prognostic factors. Gene set variation analysis was used for determining immune cell populations concomitant to NK-cell enrichment in HER2-positive tumors from the Cancer Genome Atlas (n = 190).

RESULTS:

TI-NK cells were significantly associated with pCR in the discovery cohort as well as in the validation cohort (P < 0.0001), independently of clinicopathologic factors. A ≥3 TI-NK cells/50x high-power field (HPF) cutoff predicted pCR in the discovery and validation cohort [OR, 188 (11-3154); OR, 19.5 (5.3-71.8)]. Presence of TI-NK cells associated with prolonged DFS in both patient cohorts [HR, 0.07 (0.01-0.6); P = 0.01; HR, 0.3 (0.08-1.3); P = 0.1]. NK-, activated dendritic- and CD8 T-cell gene expression signatures positively correlated in HER2-positive tumors, supporting the value of NK cells as surrogates of effective antitumor immunity. Stratification of patients by tumor HLA-I expression identified patients with low and high relapse risk independently of pCR.

CONCLUSIONS:

This study identifies baseline TI-NK cells as an independent biomarker with great predictive value for pCR to anti-HER2 antibody-based treatment and points to the complementary value of tumor HLA-I status for defining patient prognosis independently of pCR.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center