Triple-negative breast cancer: The importance of molecular and histologic subtyping, and recognition of low-grade variants Journal Article


Authors: Pareja, F.; Geyer, F. C.; Marchiò, C.; Burke, K. A.; Weigelt, B.; Reis-Filho, J. S.
Article Title: Triple-negative breast cancer: The importance of molecular and histologic subtyping, and recognition of low-grade variants
Abstract: 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.
Keywords: chemotherapy; adenoid cystic carcinoma; neoadjuvant; tumor-infiltrating lymphocytes; prognostic value; somatic mutations; salivary-glands; carcinomas; of-the-literature; secretory carcinoma; microglandular adenosis; acinic cell
Journal Title: npj Breast Cancer
Volume: 2
ISSN: 2374-4677
Publisher: Nature Publishing Group  
Date Published: 2016-11-16
Start Page: 16036
Language: English
ACCESSION: WOS:000411078100002
DOI: 10.1038/npjbcancer.2016.36
PROVIDER: wos
PMCID: PMC5515338
PUBMED: 28721389
Notes: Review -- Source: Wos
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Britta Weigelt
    632 Weigelt
  2. Kathleen   Burke
    55 Burke