Nair Isabella, Behbod Fariba
Department of General Surgery, University of Missouri - Kansas City, Kansas City, MO, USA.
Department of Pathology and Laboratory Medicine, MS 3045, The University of Kansas Medical Center, Kansas City, KS, USA.
Adv Exp Med Biol. 2025;1464:95-108. doi: 10.1007/978-3-031-70875-6_6.
An estimated 55,720 new cases of ductal carcinoma in situ (DCIS) will be diagnosed in 2023 in the USA alone because of the increased use of screening mammography. The treatment goal in DCIS is early detection and treatment with the hope of preventing progression into invasive disease. Previous studies show progression into invasive cancer as well as reduction in mortality from treatment is not as high as previously thought. So, are we overdiagnosing and over-treating DCIS? An understanding of the natural progression of DCIS is paramount to address this. The purpose of this chapter is to describe various models that have been developed to simulate the processes involved in DCIS to invasive ductal carcinoma (IDC) transition. While each model possesses a unique set of strengths and weaknesses, they have collectively contributed to the current understanding of the molecular and cellular mechanisms underlying this transition. Even though much has been learned, continued advancement of the current models to best match the composition of DCIS epithelial and stromal microenvironment including the extracellular matrix (ECM), stromal cell types, and immune microenvironment will be essential. These advances will undoubtedly pave the way toward a full understanding of mechanisms associated with progression and in predicting when a DCIS lesion remains indolent and when triggers tip in the balance toward progression to malignancy.
由于乳腺钼靶筛查的使用增加，预计仅在美国，2023年就将诊断出约55720例导管原位癌（DCIS）新病例。DCIS的治疗目标是早期发现和治疗，以期预防进展为浸润性疾病。先前的研究表明，进展为浸润性癌症以及治疗导致的死亡率降低并不像之前认为的那么高。那么，我们是否对DCIS进行了过度诊断和过度治疗呢？了解DCIS的自然进展对于解决这个问题至关重要。本章的目的是描述为模拟DCIS向浸润性导管癌（IDC）转变过程而开发的各种模型。虽然每个模型都有其独特的优缺点，但它们共同促进了目前对这一转变背后分子和细胞机制的理解。尽管已经学到了很多，但不断推进当前模型以更好地匹配DCIS上皮和基质微环境的组成，包括细胞外基质（ECM）、基质细胞类型和免疫微环境，将至关重要。这些进展无疑将为全面理解与进展相关的机制以及预测DCIS病变何时保持惰性、何时触发向恶性进展的平衡铺平道路。
