Department of Oncology and Radiotherapy, Oulu University Hospital, POB 20, 90029, Oulu, Finland.
Medical Research Center Oulu, POB 5000, 90014, Oulu, Finland.
Breast Cancer Res Treat. 2022 Jan;191(2):443-450. doi: 10.1007/s10549-021-06447-6. Epub 2021 Nov 24.
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.
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.
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.
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.
最近的研究表明，转移部位可影响肿瘤免疫特征和癌症免疫疗法的效果。HER2 阳性乳腺癌的预后与肿瘤免疫微环境的特征相关，免疫细胞在 HER2 靶向抗体的疗效中起核心作用。在此，我们研究了不同转移部位在接受曲妥珠单抗治疗的 HER2 阳性乳腺癌中的预后意义及其与肿瘤免疫特征的相关性。
我们收集了 2009 年至 2014 年在奥卢大学医院接受曲妥珠单抗联合方案治疗的所有（n=54）HER2 阳性转移性乳腺癌患者。从电子病历中收集了病理和临床数据。使用经过充分验证的免疫标志物，通过计算机辅助免疫细胞计数，从治疗前的原发肿瘤中分析肿瘤免疫特征。
在转移部位中，只有肝转移与预后不良相关（风险比 1.809，95%置信区间 1.004-3.262），尤其是肝转移作为首发转移部位时。在其他部位中，肺转移表现出一种具有改善生存趋势的患者特征。在研究的肿瘤免疫标志物中，肝转移患者的原发肿瘤中 CD3 T 细胞密度较低（p=0.030）和 M1 样巨噬细胞密度较低（p=0.025）。在其他研究的标志物和部位中，肺转移患者的原发肿瘤中 STAB1-免疫抑制性巨噬细胞密度较低。
我们的研究结果表明，转移部位与 HER2 阳性乳腺癌的预后相关，肝转移的预后较差。此外，肝转移与不良的肿瘤免疫细胞特征相关。
