Department of Pathology, Molecular Pathology Research Unit, Harvard Medical School, Boston, Massachusetts 02129, USA.
Annu Rev Pathol. 2010;5:193-221. doi: 10.1146/annurev.pathol.4.110807.092306.
Preinvasive breast cancer accounts for approximately one-third of all newly diagnosed breast cancer cases in the United States and constitutes a spectrum of neoplastic lesions with varying degrees of differentiation and clinical behavior. High-throughput genetic, epigenetic, and gene-expression analyses have enhanced our understanding of the relationship of these early neoplastic lesions to normal breast tissue, and they strongly suggest that preinvasive breast cancer develops and evolves along two distinct molecular genetic and biological pathways that correlate with tumor grade. Although unique epigenetic and gene-expression changes are not observed in the tumor epithelial compartment during the transition from preinvasive to invasive disease, distinct molecular alterations are observed in the tumor-stromal and myoepithelial cells. This suggests that the stromal and myoepithelial microenvironment of preinvasive breast cancer actively participates in the transition from preinvasive to invasive disease. An improved understanding of the transition from preinvasive to invasive breast cancer will pave the way for novel preventative and therapeutic strategies.
在美国,新诊断出的乳腺癌病例中约有三分之一为乳腺癌前期病变,它是一种具有不同分化程度和临床行为的肿瘤病变谱。高通量的遗传、表观遗传和基因表达分析增强了我们对这些早期肿瘤病变与正常乳腺组织之间关系的理解,并且强烈提示乳腺癌前期病变是沿着与肿瘤分级相关的两个不同的分子遗传和生物学途径发展和演变的。尽管在从乳腺癌前期病变到浸润性疾病的转变过程中,肿瘤上皮细胞区并未观察到独特的表观遗传和基因表达变化,但在肿瘤-基质和肌上皮细胞中观察到了明显的分子改变。这表明乳腺癌前期病变的基质和肌上皮微环境积极参与了从乳腺癌前期病变到浸润性疾病的转变。对从乳腺癌前期病变到浸润性乳腺癌的转变的深入了解将为新的预防和治疗策略铺平道路。