Abstract
PurposeRecent 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.MethodsWe 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.ResultsOf 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.ConclusionOur 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.
Highlights
Around 20% of all breast cancers have amplification of the human epidermal growth factor receptor 2 (HER2), which had been associated with aggressive tumour type and poor prognosis, before targeted therapies for HER2 were developed [1,2,3,4]
The metastatic pattern varies in different breast cancer subtypes; all subtypes are prone to metastasize to the bone, but brain and liver metastases are more often seen in HER2 positive and triple-negative breast cancers [8,9,10,11,12]
In our previous studies with metastatic H ER2+ breast cancer[14, 15], we found that high infiltration of both CD8+ T cells and M1-like macrophages in the centre of the tumour (CT) were associated with improved survival
Summary
Around 20% of all breast cancers have amplification of the human epidermal growth factor receptor 2 (HER2), which had been associated with aggressive tumour type and poor prognosis, before targeted therapies for HER2 were developed [1,2,3,4]. Immunology is suggested to play a major role in influencing the prognosis in HER2-positive breast cancer and treatment efficiency of HER2-targeted antibodies. In all subtypes of breast cancer, the most common sites of metastasis are bone, liver,. Breast Cancer Research and Treatment lung, and brain. Bone metastases have often been linked to better prognosis, whereas patients with brain metastases are known to have the worst prognosis, especially in de novo stage IV breast cancers [8, 9]. The metastatic pattern varies in different breast cancer subtypes; all subtypes are prone to metastasize to the bone, but brain and liver metastases are more often seen in HER2 positive and triple-negative breast cancers [8,9,10,11,12]
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