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Intratumoral Heterogeneity in Ductal Carcinoma In Situ: Chaos and Consequence

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Abstract

Ductal carcinoma in situ (DCIS) is a non-invasive proliferative growth in the breast that serves as a non-obligate precursor to invasive ductal carcinoma. The widespread adoption of screening mammography has led to a steep increase in the detection of DCIS, which now comprises approximately 20% of new breast cancer diagnoses in the United States. Interestingly, the intratumoral heterogeneity (ITH) that has been observed in invasive breast cancers may have been established early in tumorigenesis, given the vast and varied ITH that has been detected in DCIS. This review will discuss the intratumoral heterogeneity of DCIS, focusing on the phenotypic and genomic heterogeneity of tumor cells, as well as the compositional heterogeneity of the tumor microenvironment. In addition, we will assess the spatial heterogeneity that is now being appreciated in these lesions, and summarize new approaches to evaluate heterogeneity of tumor and stromal cells in the context of their spatial organization. Importantly, we will discuss how a growing understanding of ITH has led to a more holistic appreciation of the complex biology of DCIS, specifically its evolution and natural history. Finally, we will consider ways in which our knowledge of DCIS ITH might be translated in the future to guide clinical care for DCIS patients.

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Acknowledgements

The authors would like to acknowledge Drs. Fariba Behbod and Jason I. Herschkowitz for editorial support, as well as Drs. Amanda L. Rinkenbaugh and Abena B. Redwood for critical evaluation and proof reading of this article. This work was supported by the Stand Up To Cancer Laura Ziskin Prize (to HPW) and by the Department of Defense through the Breast Cancer Research Program under Award No. W81XWH-17-1-0077 (to VCS).

Funding

This work was supported by the Stand Up To Cancer Laura Ziskin Prize (to HPW) and by the Department of Defense through the Breast Cancer Research Program under Award No. W81XWH-17-1-0077 (to VCS). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.

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  1. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX, 77030, USA

    Vidya C. Sinha & Helen Piwnica-Worms

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  1. Vidya C. Sinha
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Correspondence to Helen Piwnica-Worms.

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Sinha, V.C., Piwnica-Worms, H. Intratumoral Heterogeneity in Ductal Carcinoma In Situ: Chaos and Consequence. J Mammary Gland Biol Neoplasia 23, 191–205 (2018). https://doi.org/10.1007/s10911-018-9410-6

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