Unit of Pathology, Candiolo Cancer Institute, FPO IRCCS, Candiolo, Italy.
Department of Medical Sciences, University of Turin, Turin, Italy.
Pathobiology. 2020;87(2):125-142. doi: 10.1159/000507055. Epub 2020 Apr 23.
Heterogeneity in breast carcinomas can be appreciated at various levels, from morphology to molecular alterations, and there are well-known genotypic-phenotypic correlations. Clinical decision-making is strictly focused on the evaluation of tumor cells and is based on the assessment of hormone receptors and of the HER2 status, by means of a combination of immunohistochemical and in situ hybridization techniques. The tumor microenvironment (TME) also shows a multifaceted nature stemming from the different actors populating the intratumoral and the peritumoral stroma of breast carcinomas. Of note, we have now evidence that tumor-infiltrating lymphocytes (TILs) are clinically meaningful as their quantification in the intratumoral stroma strongly correlates with good prognosis, in particular in triple-negative and HER2-positive breast cancer patients. Nevertheless, TILs are just one of the many actors orchestrating the complexity of the TME, which is populated by immune and non-immune cells (cancer-associated fibroblasts, cancer-associated adipocytes), as well as non-cellular components such as chemical inflammation mediators. In this review article we will overview the main features of the distinct cell compartments by discussing (i) the potential impact the TME may have on the prognostic stratification of breast cancers and (ii) the possible predictive value of some markers in the context of immunotherapy in light of the recent results of phase III studies in advanced and early triple-negative breast cancer patients.
乳腺癌的异质性可在多个层面上得到体现，从形态学到分子改变，并且存在着众所周知的基因型-表型相关性。临床决策严格聚焦于肿瘤细胞的评估，并基于对激素受体和 HER2 状态的评估，通过免疫组织化学和原位杂交技术的组合来实现。肿瘤微环境（TME）也表现出多面性，源于不同的细胞成分在乳腺癌的肿瘤内和肿瘤周围基质中存在。值得注意的是，我们现在有证据表明，肿瘤浸润淋巴细胞（TILs）具有临床意义，因为它们在肿瘤内基质中的定量与良好的预后密切相关，特别是在三阴性和 HER2 阳性乳腺癌患者中。然而，TILs 只是众多调节 TME 复杂性的因素之一，TME 中还存在免疫和非免疫细胞（癌相关成纤维细胞、癌相关脂肪细胞）以及非细胞成分，如化学炎症介质。在这篇综述文章中，我们将通过讨论（i）TME 可能对乳腺癌的预后分层产生的潜在影响，以及（ii）一些标志物在免疫治疗背景下的可能预测价值，来概述不同细胞区室的主要特征，这些标志物是基于晚期和早期三阴性乳腺癌患者的 III 期研究的最新结果得出的。
