传统上，乳腺癌的分类依靠于临床实践中易得的免疫组织化学（IHC）生物标志物的表达。通过在患者群中使用高度标准化和可重复的检测方法，基于50个基因表达的乳腺癌内在分子亚型，也被称为“内在亚型”（IS），已经被鉴定出来。虽然基于IHC的亚组和IS之间有中等程度的相关性，但它们并不是重合的。事实上，在激素受体阳性（HoR+）肿瘤中，大约5-20%的患者存在非泌乳型生物学特征，具有预后价值，并分别识别出内分泌治疗和化疗的降低和增加敏感性。在肿瘤进展过程中，向非泌乳性质不依赖雌激素的更具侵袭性表型的转变已经被证实。内在基因组不稳定和细胞可塑性，单独或与治疗选择性压力或与肿瘤微环境相互作用相结合，可能代表了初发性和转移性疾病之间的生物多样性以及肿瘤转移过程中的决定因素。在本综述中，我们描述了IS随着疾病进展的分布和临床行为，重点关注HoR+/HER2阴性晚期乳腺癌。此外，我们提供了正在进行的临床试验的概述，旨在验证IS的预测和预后价值，以便将其纳入日常护理。版权所有©2022年作者。由Elsevier Ltd.出版。保留所有权利。

Traditionally, the classification of breast cancer relies on the expression of immunohistochemical (IHC) biomarkers readily available in clinical practice. Using highly standardized and reproducible assays across patient cohorts, intrinsic molecular subtypes of breast cancer - also called "intrinsic subtypes" (IS) - have been identified based on the expression of 50 genes. Although IHC-based subgroups and IS moderately correlate to each other, they are not superimposable. In fact, non-luminal biology has been detected in a substantial proportion (5-20%) of hormone receptor-positive (HoR+) tumors, has prognostic value, and identifies reduced and increased sensitivity to endocrine therapy and chemotherapy, respectively. During tumor progression, a shift toward a non-luminal estrogen-independent and more aggressive phenotype has been demonstrated. Intrinsic genomic instability and cell plasticity, alone or combined with external constraints deriving from treatment selective pressure or interplay with the tumor microenvironment, may represent the determinants of such biological diversity between primary and metastatic disease, and during metastatic tumor evolution. In this review, we describe the distribution and the clinical behavior of IS as the disease progresses, focusing on HoR+/HER2-negative advanced breast cancer. In addition, we provide an overview of the ongoing clinical trials aiming to validate the predictive and prognostic value of IS towards their incorporation into routine care.Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.