Pareja Fresia, Geyer Felipe C, Marchiò Caterina, Burke Kathleen A, Weigelt Britta, Reis-Filho Jorge S
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medical Sciences, University of Turin, Turin, Italy.
NPJ Breast Cancer. 2016 Nov 16;2:16036. doi: 10.1038/npjbcancer.2016.36. eCollection 2016.
Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.
三阴性乳腺癌（TNBC）定义为雌激素受体、孕激素受体及HER2均不表达，占乳腺癌的12%-17%，在临床上被视为一个独立的乳腺癌亚组。尽管如此，TNBC已被证明是一种高度异质性疾病，涵盖了广泛的实体，在基因、转录、组织学和临床方面存在显著差异。虽然大多数TNBC是高级别肿瘤，但也有特征明确的低级别TNBC，其临床病程较为惰性，其自然史、分子特征和最佳治疗方法与高级别TNBC有很大不同。分泌性癌和腺样囊性癌是由特定融合基因支持的两种TNBC组织学类型；这些肿瘤具有惰性的临床行为，缺乏高级别三阴性疾病的所有主要分子特征。最近对罕见实体的研究，包括一些曾被认为仅仅是良性乳腺疾病的病变（如微腺性腺病），已导致TNBC潜在前体的识别，并提示存在一系列低级别三阴性病变，尽管它们具有低级别形态和惰性临床行为，但已被证明具有常见形式TNBC的复杂基因组格局，并且可能进展为高级别疾病。在本综述中，我们描述了TNBC的异质性，并重点关注低级别TNBC的组织学和分子特征。认识到TNBC仅仅是一个描述性术语，以及低级别TNBC类型可能由不同的基因改变驱动，这与应对所谓三阴性疾病带来的挑战密切相关。
