Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance

Abstract

Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25–60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.

Dynamic HSF2 regulation drives breast cancer progression by steering the balance between proliferation and invasion

“…Based on our data from transcriptional, protein, and functional analyses, we connect the consequences of HSF2 activation with induced cell proliferation. Ki67 is commonly used as a prognostic marker for invasive breast cancer and its high levels are associated with an elevated risk of DCIS recurrence (Davis et al, 2016; Poulakaki et al, 2018; Wang et al, 2024). However, the drivers of the invasive transition from DCIS to IDC are still poorly characterized and the current biomarkers are unable to reliably distinguish the high-risk lesions (Wang et al, 2024).…”

“…Ki67 is commonly used as a prognostic marker for invasive breast cancer and its high levels are associated with an elevated risk of DCIS recurrence (Davis et al, 2016; Poulakaki et al, 2018; Wang et al, 2024). However, the drivers of the invasive transition from DCIS to IDC are still poorly characterized and the current biomarkers are unable to reliably distinguish the high-risk lesions (Wang et al, 2024). To this end, this study provides strong advancement in the diagnostics of breast cancer progression.…”

“…Although DCIS has a good prognosis, it is also considered as the non-obligate precursor of invasive ductal carcinoma (IDC). Yet the drivers of the invasive transition remain poorly characterized, obscuring the reliable identification of high-risk lesions (Wilson et al, 2022; Wang et al, 2024). In IDC, neoplastic epithelial cells have breached through the basement membrane and evaded the ductal confinement into the surrounding stromal tissue (Lo et al, 2017; Wilson et al, 2022; Wang et al, 2024).…”

“…Yet the drivers of the invasive transition remain poorly characterized, obscuring the reliable identification of high-risk lesions (Wilson et al, 2022; Wang et al, 2024). In IDC, neoplastic epithelial cells have breached through the basement membrane and evaded the ductal confinement into the surrounding stromal tissue (Lo et al, 2017; Wilson et al, 2022; Wang et al, 2024). The transition from DCIS to IDC is initiated by a subset of transformed cells that unlock the restricted capacity of phenotypic plasticity.…”

Are Meteorin-Like Peptide and Asprosin Important in the Diagnosis of Breast Tumors?

“…However, it is difficult to predict whether DCIS will turn into IDC. The mechanisms that cause progression from DCIS to IDC are still not fully understood [ 9 ]. Based on this problem, in this study, the roles of these proteins in the diagnosis of breast IDC were investigated by examining the presence and level of METRNL and asprosin in the neoplastic tissues of the breast with IDC.…”