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What is the malignant nature of human ductal carcinoma in situ?

Nature Reviews Cancer volume 11, pages 68–75 (2011)Cite this article

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Abstract

Invasive, genetically abnormal carcinoma progenitor cells have been propagated from human and mouse breast ductal carcinoma in situ (DCIS) lesions, providing new insights into breast cancer progression. The survival of DCIS cells in the hypoxic, nutrient-deprived intraductal niche could promote genetic instability and the derepression of the invasive phenotype. Understanding potential survival mechanisms, such as autophagy, that might be functioning in DCIS lesions provides strategies for arresting invasion at the pre-malignant stage. A new, open trial of neoadjuvant therapy for patients with DCIS constitutes a model for testing investigational agents that target malignant progenitor cells in the intraductal niche.

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Figure 1: The stressful microenvironment of the intraductal niche may promote genetic instability.
Figure 2: Autophagy and cell survival in DCIS lesions.
Figure 3: Upstream pathways that intersect with the autophagic pathway.
Figure 4: A neoadjuvant therapy trial for DCIS.

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Acknowledgements

This work was funded in part by a Department of Defense Breast Cancer Research Program award, W81XWH-07-1-0377, to L.A.L. The authors would like to thank K. Edmiston for her role as clinical PI of the trial described in figure 4. The authors also thank B. Mariani and K. Tran, Genetics & IVF Institute, for genetic analysis of DCIS cells.

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  1. Virginia Espina and Lance A. Liotta are at the George Mason University, Center for Applied Proteomics and Molecular Medicine, 10900 University Boulevard, MS1A9, Manassas, Virginia 20110, USA.,

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Correspondence to Lance A. Liotta.

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Espina, V., Liotta, L. What is the malignant nature of human ductal carcinoma in situ?. Nat Rev Cancer 11, 68–75 (2011). https://doi.org/10.1038/nrc2950

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