Santagata Sandro, Ince Tan A
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Expert Rev Anticancer Ther. 2014 Dec;14(12):1385-9. doi: 10.1586/14737140.2014.956096. Epub 2014 Sep 27.
The current classification system for breast cancer is based on expression of empirical prognostic and predictive biomarkers. As an alternative, we propose a hypothesis-based ontological breast cancer classification modeled after the taxonomy of species in evolutionary biology. This approach uses normal breast epithelial cell types and differentiation lineages as the gold standard to classify tumors. We show that there are at least eleven previously undefined normal cell types in human breast epithelium and that each breast carcinoma is related to one of these normal cell types. We find that triple negative breast cancers do not have a 'basal-like' phenotype. Normal breast epithelial cells conform to four novel hormonal differentiation states and almost all human breast tumors duplicate one of these hormonal differentiation states which have significant survival differences. This ontological classification scheme provides actionable treatment strategies and provides an alternative approach for understanding tumor biology with wide-ranging implications for tumor taxonomy.
当前的乳腺癌分类系统基于经验性预后和预测生物标志物的表达。作为一种替代方案，我们提出了一种基于假设的本体论乳腺癌分类方法，该方法以进化生物学中物种的分类法为模型。这种方法使用正常乳腺上皮细胞类型和分化谱系作为对肿瘤进行分类的金标准。我们表明，人类乳腺上皮中至少有11种先前未定义的正常细胞类型，并且每种乳腺癌都与这些正常细胞类型之一相关。我们发现三阴性乳腺癌不具有“基底样”表型。正常乳腺上皮细胞符合四种新的激素分化状态，几乎所有人类乳腺肿瘤都重复这些具有显著生存差异的激素分化状态之一。这种本体论分类方案提供了可操作的治疗策略，并为理解肿瘤生物学提供了一种替代方法，对肿瘤分类学具有广泛的影响。
