Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Mol Oncol. 2013 Oct;7(5):859-69. doi: 10.1016/j.molonc.2013.07.005. Epub 2013 Jul 12.
Ductal carcinoma in situ (DCIS) is an intraductal neoplastic proliferation of epithelial cells that is separated from the breast stroma by an intact layer of basement membrane and myoepithelial cells. DCIS is a non-obligate precursor of invasive breast cancer, and up to 40% of these lesions progress to invasive disease if untreated. Currently, it is not possible to predict accurately which DCIS would be more likely to progress to invasive breast cancer as neither the significant drivers of the invasive transition have been identified, nor has the clinical utility of tests predicting the likelihood of progression been demonstrated. Although molecular studies have shown that qualitatively, synchronous DCIS and invasive breast cancers are remarkably similar, there is burgeoning evidence to demonstrate that intra-tumor genetic heterogeneity is observed in a subset of DCIS, and that the process of progression to invasive disease may constitute an 'evolutionary bottleneck', resulting in the selection of subsets of tumor cells with specific genetic and/or epigenetic aberrations. Here we review the clinical challenge posed by DCIS, the contribution of the microenvironment and genetic aberrations to the progression from in situ to invasive breast cancer, the emerging evidence of the impact of intra-tumor genetic heterogeneity on this process, and strategies to combat this heterogeneity.
导管原位癌（DCIS）是一种上皮细胞的导管内肿瘤性增生，与乳腺基质之间由完整的基底膜和肌上皮细胞分隔开。DCIS 是浸润性乳腺癌的非强制性前体，高达 40%的未治疗病变会进展为浸润性疾病。目前，由于尚未确定浸润性转化的主要驱动因素，也未证明预测进展可能性的测试具有临床实用性，因此无法准确预测哪些 DCIS 更有可能进展为浸润性乳腺癌。尽管分子研究表明，在质量上，同步的 DCIS 和浸润性乳腺癌非常相似，但越来越多的证据表明，在一部分 DCIS 中观察到肿瘤内遗传异质性，并且进展为浸润性疾病的过程可能构成“进化瓶颈”，导致具有特定遗传和/或表观遗传异常的肿瘤细胞亚群被选择。在这里，我们回顾了 DCIS 带来的临床挑战，微环境和遗传异常对原位至浸润性乳腺癌进展的贡献，以及肿瘤内遗传异质性对这一过程的影响的新证据，以及对抗这种异质性的策略。
