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Breaking through to the Other Side: Microenvironment Contributions to DCIS Initiation and Progression

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Abstract

Refinements in early detection, surgical and radiation therapy, and hormone receptor-targeted treatments have improved the survival rates for breast cancer patients. However, the ability to reliably identify which non-invasive lesions and localized tumors have the ability to progress and/or metastasize remains a major unmet need in the field. The current diagnostic and therapeutic strategies focus on intrinsic alterations within carcinoma cells that are closely associated with proliferation. However, substantial accumulating evidence has indicated that permissive changes in the stromal tissues surrounding the carcinoma play an integral role in breast cancer tumor initiation and progression. Numerous studies have suggested that the stromal environment surrounding ductal carcinoma in situ (DCIS) lesions actively contributes to enhancing tumor cell invasion and immune escape. This review will describe the current state of knowledge regarding the mechanisms through which the microenvironment interacts with DCIS lesions focusing on recent studies that describe the contributions of myoepithelial cells, fibroblasts and immune cells to invasion and subsequent progression. These mechanisms will be considered in the context of developing biomarkers for identifying lesions that will progress to invasive carcinoma and/or developing approaches for therapeutic intervention.

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Acknowledgements

The authors would like to acknowledge Dr. Molly Klein for providing images. This work was supported by Minnesota Masonic Charities Eastern Star Scholarship (A.C.N.), Susan G. Komen CCR16377665 (H.L.M), NIH R01 CA212518 (H.L.M.) and NIH R01 CA215052 (K.L.S.).

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    Andrew C. Nelson & Kathryn L. Schwertfeger

  2. Masonic Cancer Center, University of Minnesota, 2231 6th St SE, Minneapolis, MN, 55455, USA

    Andrew C. Nelson & Kathryn L. Schwertfeger

  3. Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA

    Heather L. Machado

  4. Center for Immunology, University of Minnesota, Minneapolis, MN, USA

    Kathryn L. Schwertfeger

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  1. Andrew C. Nelson
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Correspondence to Kathryn L. Schwertfeger.

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Nelson, A.C., Machado, H.L. & Schwertfeger, K.L. Breaking through to the Other Side: Microenvironment Contributions to DCIS Initiation and Progression. J Mammary Gland Biol Neoplasia 23, 207–221 (2018). https://doi.org/10.1007/s10911-018-9409-z

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