Immune cell profiles of metastatic HER2-positive breast cancer patients according to the sites of metastasis

Breast Cancer Res Treat. 2022 Jan;191(2):443-450. doi: 10.1007/s10549-021-06447-6. Epub 2021 Nov 24.

Abstract

Purpose: Recent works have characterized that metastatic site can affect the tumour immune profiles and efficiency of cancer immunotherapies. The prognosis of HER2-positive breast cancer is associated with the characteristics of the tumour immune microenvironment, with immunological cells playing a central role in efficiency of HER2-targeted antibodies. Here we investigated the prognostic significance of different metastatic sites and their correlation to tumour immune profiles in HER2-positive breast cancer treated with trastuzumab.

Methods: We collected all (n = 54) HER2-positive metastatic breast cancer patients treated with trastuzumab containing regimens at Oulu University Hospital 2009-2014. Pathological and clinical data were collected from electronic patient records. The tumour immune profiles were analysed from pre-treatment primary tumours using well-characterized immunological markers with computer-assisted immune cell counting.

Results: Of the metastatic sites, only liver metastases were associated with poor prognosis (hazard ratio 1.809, 95% confidence interval 1.004-3.262), especially when presented as the primary site of metastases. Of the other sites, pulmonary metastases characterized a patient profile with trend to improved survival. Of the studied tumour immunological markers, patients with liver metastases had low densities of CD3+ T cells (p = 0.030) and M1-like macrophages in their primary tumours (p = 0.025). Of the other studied markers and sites, patients with pulmonary metastases had low STAB1+-immunosuppressive macrophage density in their primary tumours.

Conclusion: Our results suggest that the site of metastasis is associated with prognosis in HER2-positive breast cancer, highlighted by the poor prognosis of liver metastases. Furthermore, liver metastases were associated with adverse tumour immune cell profiles.

Keywords: Breast cancer; HER2; Liver metastasis; Tumour profiles.

MeSH terms

  • Biomarkers, Tumor
  • Breast Neoplasms* / drug therapy
  • Female
  • Humans
  • Neoplasm Metastasis
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Trastuzumab / therapeutic use
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor
  • Receptor, ErbB-2
  • Trastuzumab