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Ann Oncol. 2014 Aug;25(8):1544-50. doi: 10.1093/annonc/mdu112. Epub 2014 Mar 7.

Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial.

Author information

1
Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium Division of Research and Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne,Australia sherene.loi@petermac.org.
2
Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium Service de Biostatistique et D'Epidemiology, Gustave Roussy, Universite Paris-Sud, Villejuif, France.
3
Department of Anatomical Pathology, Institut Jules Bordet, Brussels, Belgium.
4
Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
5
Department of Oncology, Tampere University Hospital, Tampere.
6
Department of Oncology, Helsinki University Central Hospital, Helsinki.
7
Cancer Center, Kuopio University Hospital, Kuopio, Finland.
8
Department of Medicine, Institut Jules Bordet, Brussels, Belgium.
9
German Breast Group, Neu-Isenburg.
10
Charité University Hospital, Institute of Pathology, Berlin, Germany.
11
Immunology in Cancer and Infection Laboratory, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute; School of Medicine, University of Queensland, Herston, Australia.

Abstract

BACKGROUND:

We have previously shown the prognostic importance of tumor-infiltrating lymphocytes (TILs) in newly diagnosed triple-negative breast cancer (TNBC) using tumor samples from a large clinical trial cohort. In this study, we aimed to validate these findings and also investigate associations with trastuzumab benefit in HER2-overexpressing disease (HER2+).

PATIENTS AND METHODS:

A prospective-retrospective study was conducted using samples from the FinHER adjuvant, phase III trial that enrolled 1010 early-stage BC patients, 778 of whom were HER2-nonamplified. Those with HER2+ disease (n = 232) were randomized to 9 weeks of trastuzumab or no trastuzumab in addition to chemotherapy. Two pathologists independently quantified stromal TILs in 935 (92.6%) available slides. The primary end point of distant disease-free survival (DDFS) and interactions with trastuzumab were studied in Cox regression models.

RESULTS:

Confirming our previous findings, in TNBC (n = 134) each 10% increase in TILs was significantly associated with decreased distant recurrence in TNBC; for DDFS the hazard ratio adjusted for clinicopathological factors: 0.77; 95% confidence interval (CI) 0.61-0.98, P = 0.02. In HER2+ BC (n = 209), each 10% increase in lymphocytic infiltration was significantly associated with decreased distant recurrence in patients randomized to the trastuzumab arm (DDFS P interaction = 0.025).

CONCLUSIONS:

Higher levels of TILs present at diagnosis were significantly associated with decreased distant recurrence rates in primary TNBC. These results confirm our previous data and further support that TILs should be considered as a robust prognostic factor in this BC subtype. We also report for the first time an association between higher levels of TILs and increased trastuzumab benefit in HER2+ disease. Further research into why some TN and HER2+ BCs can or cannot generate a host antitumor immune response and how trastuzumab can favorably alter the immune microenvironment is warranted.

KEYWORDS:

TILs; biomarkers trastuzumab efficacy; breast cancer; lymphocytic infiltration; prediction; prognosis

PMID:
24608200
DOI:
10.1093/annonc/mdu112
[Indexed for MEDLINE]

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