What question did this study set out to answer?

To explore how the tumor microenvironment impacts recurrence and progression of ductal carcinoma in situ (DCIS).

December 8, 2025

Abstract A016: Microenvironmental drivers of DCIS recurrence and progression to breast cancer

Key Points

To explore how the tumor microenvironment impacts recurrence and progression of ductal carcinoma in situ (DCIS).
Conducted a retrospective cohort study of 158 patients with DCIS diagnosis.
Utilized machine learning guided nuclear segmentation on digital pathology images.
Calculated spatial statistics to analyze tumor microenvironment interactions.
Employed a linear spline-based hazard regression model for survival prediction.
Type of DCIS treatment significantly stratified patients by disease-free survival (p<0.0001).
Decreased nearest neighbor distance between tumor cells and lymphocytes linked to improved recurrence-free survival (concordance=0.68).
Median risk score stratification showed discriminatory potential (p<0.015).
Near distance between lymphocytes and fibroblasts marginally linked to increased time to invasive disease (p<0.06).

Abstract

Abstract Background Studies show that only 20–30% of untreated ductal carcinoma in situ (DCIS) cases will evolve into invasive breast cancer. Thus, many patients are subject to overtreatment and its associated morbidities. The ecological context of the tumor microenvironment may impact how DCIS evolves. We applied landscape ecology statistics to hematoxylin and eosin (H0. 0001). Further analysis of patients who received lumpectomy + radiation or mastectomy revealed that decreased mean nearest neighbor distance between tumor cells and lymphocytes, and between fibroblasts and lymphocytes, was significantly associated with improved recurrence-free survival (concordance=0. 68). Stratification of samples based on the median risk score derived from our model was discriminatory with a p-value 0. 015. Additionally, a decreased nearest neighbor distance between lymphocytes and fibroblasts showed a marginal association with an increased time to invasive disease (p0. 06). Conclusions Integrating spatial ecological statistics derived from digital pathology provides enhanced risk stratification for DCIS, beyond the established effects of initial treatment. Our findings underscore the importance of the tumor microenvironment's ecological dynamics in DCIS recurrence and progression. The predictive risk associated with specific spatial interactions, particularly involving lymphocytes and fibroblasts, suggests that previously unappreciated ecological mechanisms may play a role in the development of early micro-metastases, influencing outcomes even after standard therapies such as mastectomy or lumpectomy with radiation. These insights highlight novel targets for improved prognostic tools and more personalized therapeutic strategies. Citation Format: Luis H. Cisneros. Microenvironmental drivers of DCIS recurrence and progression to breast cancer abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85 (23Suppl): Abstract nr A016.

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Cite This Study

Luis H. Cisneros (Thu,) studied this question.

synapsesocial.com/papers/693624ce4fa91c937236cf4e https://doi.org/https://doi.org/10.1158/1538-7445.canevol25-a016

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