Nelson Andrew C, Machado Heather L, Schwertfeger Kathryn L
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Masonic Cancer Center, University of Minnesota, 2231 6th St SE, Minneapolis, MN, 55455, USA.
J Mammary Gland Biol Neoplasia. 2018 Dec;23(4):207-221. doi: 10.1007/s10911-018-9409-z. Epub 2018 Aug 31.
Refinements in early detection, surgical and radiation therapy, and hormone receptor-targeted treatments have improved the survival rates for breast cancer patients. However, the ability to reliably identify which non-invasive lesions and localized tumors have the ability to progress and/or metastasize remains a major unmet need in the field. The current diagnostic and therapeutic strategies focus on intrinsic alterations within carcinoma cells that are closely associated with proliferation. However, substantial accumulating evidence has indicated that permissive changes in the stromal tissues surrounding the carcinoma play an integral role in breast cancer tumor initiation and progression. Numerous studies have suggested that the stromal environment surrounding ductal carcinoma in situ (DCIS) lesions actively contributes to enhancing tumor cell invasion and immune escape. This review will describe the current state of knowledge regarding the mechanisms through which the microenvironment interacts with DCIS lesions focusing on recent studies that describe the contributions of myoepithelial cells, fibroblasts and immune cells to invasion and subsequent progression. These mechanisms will be considered in the context of developing biomarkers for identifying lesions that will progress to invasive carcinoma and/or developing approaches for therapeutic intervention.
早期检测、手术和放射治疗以及激素受体靶向治疗的改进提高了乳腺癌患者的生存率。然而，可靠地识别哪些非侵袭性病变和局限性肿瘤具有进展和/或转移能力的能力，仍然是该领域尚未满足的主要需求。目前的诊断和治疗策略侧重于癌细胞内与增殖密切相关的内在改变。然而，大量越来越多的证据表明，癌周围基质组织的允许性变化在乳腺癌肿瘤的起始和进展中起着不可或缺的作用。许多研究表明，原位导管癌（DCIS）病变周围的基质环境积极促进肿瘤细胞侵袭和免疫逃逸。本综述将描述关于微环境与DCIS病变相互作用机制的当前知识状态，重点关注最近描述肌上皮细胞、成纤维细胞和免疫细胞对侵袭及随后进展的贡献的研究。将在开发用于识别将进展为浸润性癌的病变的生物标志物或开发治疗干预方法的背景下考虑这些机制。
