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

Sep 21, 2026

Progression from ductal carcinoma in situ (DCIS) to invasive breast cancer (IDC) remains challenging to predict, since untreated DCIS can advance to IDC in roughly 25–60% of cases. This review summarizes signaling pathways potentially driving DCIS initiation and the DCIS–IDC transition, and compares molecular features across DCIS and IDC, including tumor-intrinsic alterations and tumor microenvironment changes. It also consolidates research tools such as preclinical models, single-cell sequencing, spatial transcriptomics, and artificial intelligence, and discusses prognostic biomarkers and clinical management advances to support more personalized treatment strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages28

Reading Time1 h 11 min

AccessFree to download

INTRODUCTION

DCIS as a pre-invasive stage and clinical challenge

Histologic and intrinsic subtype frameworks

Molecular features and risk/prognosis considerations

REVIEW SCOPE AND SUMMARY

Key signaling pathways and DCIS–IDC transition mechanisms

Research tools: preclinical models, single-cell, spatial transcriptomics, AI

Clinical advancements: biomarkers and management

Signal Transduction [and Targeted Therapy](and Targeted Therapy www.nature.com/sigtrans)[ www.nature.com/sigtrans](and Targeted Therapy www.nature.com/sigtrans) REVIEW ARTICLE OPEN Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical signiﬁcance Jing Wang 1,2,3, Baizhou Li4, Meng Luo1,3,5, Jia Huang 1,3, Kun Zhang2, Shu Zheng 1,3, Suzhan Zhang 1,3 ✉ and Jiaojiao Zhou 1,2,3,6 ✉ | | 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 overor 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. | | | | | Signal Transduction and Targeted Therapy (2024)9:83 ; [https://doi.org/10.1038/s41392-024-01779-3](https://doi.org/10.1038/s41392-024-01779-3) | | | | | | INTRODUCTION Ductal carcinoma in situ (DCIS) is a stage 0 breast cancer characterized by the abnormal proliferation of epithelial cells within the ductal-lobular system of the breast. It accounts for approximately 20% cases of newly diagnosed breast cancer.1–3 Based on architectural patterns, DCIS has been classiﬁed into comedo, papillary, solid, cribriform, and micropapillary subtypes.4 Based on the histopathologic nuclear features, DCIS can present asa spectrum, with low-grade (I), intermediate-grade (II), and highgrade (III) lesions; the latter are associated with a higher likelihood of invasive ductal carcinoma (IDC) .5,6 DCIS is commonly considered as a direct precursor to IDC. Studies have reported that approximately 25–60% of untreated DCIS cases progressed to IDC within 9–24 years of follow-up, based on the limited sample size statistics.7–10 However, the natural history and deﬁnite etiology of these two disease classiﬁcations remain poorly understood. Nevertheless, the development of novel technologies has offered new insights into these lesions. In this context, discoveries related to the initiation and progression of DCIS and IDC are essential for further investigation into their origin and clinical management. DCIS is often categorized as non-invasive or pre-invasive stage of breast cancer. Nonetheless, our understanding of the underlying causes of DCIS as well as how it progressed to be invasive is limited.11, 12 Notably, similarities and differences have been observed between DCIS and IDC. Over the years, the rapid increase in the incidence of DCIS has accompanied the widespread adoption of mammography (mostly based on screening-detected calciﬁcations) .13–15 In this context, mammographic calciﬁcation is more f

FAQs

What problem does the review address in DCIS management?

It targets the difficulty of distinguishing non-progressive from progressive DCIS, which can lead to over- or under-treatment.

How does DCIS differ from invasive ductal carcinoma at the tissue level?

DCIS cells remain confined to the mammary ductal-lobular system with intact myoepithelial layer and basement membrane, whereas IDC escapes the myoepithelial layer and invades surrounding tissue.

Which research tools are summarized for studying DCIS and IDC?

The review systematically summarizes preclinical models and newer technologies including single-cell sequencing, spatial transcriptomics, and artificial intelligence.

Sep 21, 2026

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