University of Oulu

Honkanen, T., Moilanen, T., Karihtala, P., Tiainen, S., Auvinen, P., Väyrynen, J., Mäkinen, M., Koivunen, J. (2017) Prognostic and predictive role of spatially positioned tumour infiltrating lymphocytes in metastatic HER2 positive breast cancer treated with trastuzumab. Scientific Reports, 7 (1). doi:10.1038/s41598-017-18266-1

Prognostic and predictive role of spatially positioned tumour infiltrating lymphocytes in metastatic HER2 positive breast cancer treated with trastuzumab

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Author: Honkanen, Tiia J.1,2,3; Moilanen, Tiina1,2,3; Karihtala, Peeter1,2,3;
Organizations: 1Department of Oncology and Radiotherapy, Oulu University Hospital
2University of Oulu
3Medical Research Center Oulu
4Cancer Center, Kuopio University Hospital
5University of Eastern Finland, Kuopio
6Cancer and Translational Medicine Research Unit, University of Oulu
7Department of Pathology, Oulu University Hospital
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.9 MB)
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Language: English
Published: Springer Nature, 2017
Publish Date: 2018-02-08


Disease outcomes of HER2+ breast cancers have dramatically changed after targeted therapies, such as trastuzumab, came to clinical practice but predictive factors for trastuzumab sensitivity and resistance are frequently unknown. Current work included metastatic breast cancer patients (n = 48), who were treated with trastuzumab and had pre-treatment tumour samples available. The tumours were immunostained for T-cell (CD3, CD8), natural killer (NK)-cell (CD56) and macrophage (CD68) markers and quantitative analysis of the immune cells was carried out using a computer-assisted image analysis in different tumour locations. High number of CD3 and CD8 positive T-cells was associated with significant survival benefit in the center of the tumour (CT) (p = 0.007, p = 0.001) but not in the invasive margin. The number of NK-cells and macrophages in the CT showed non-significant tendency towards improved survival. In subgroup analyses, high density of CD8 CT cells was associated with significant survival benefit in non-bone only disease, in TX or T1-3, and in ER+ tumours (p = 0.006, p = 0.003, p = 0.001). Moreover, high CD8 CT cell density associated significantly with long trastuzumab interruption periods in response. The results suggest important prognostic and predictive role of tumour infiltrating lymphocytes in center of the tumours in metastatic HER2+ breast cancer.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 7
Issue: 1
Article number: 18027
DOI: 10.1038/s41598-017-18266-1
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by the University of Oulu, Oulu University Hospital, and Finnish Cancer Institute.
Copyright information: © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.