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Effects of Tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers

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Abstract

Mammographic density (MD) is a strong risk factor for breast cancer. It is altered by exogenous endocrine treatments, including hormone replacement therapy and Tamoxifen. Such agents also modify breast cancer (BC) risk. However, the biomolecular basis of how systemic endocrine therapy modifies MD and MD-associated BC risk is poorly understood. This study aims to determine whether our xenograft biochamber model can be used to study the effectiveness of therapies aimed at modulating MD, by examine the effects of Tamoxifen and oestrogen on histologic and radiographic changes in high and low MD tissues maintained within the biochamber model. High and low MD human tissues were precisely sampled under radiographic guidance from prophylactic mastectomy fresh specimens of high-risk women, then inserted into separate vascularized murine biochambers. The murine hosts were concurrently implanted with Tamoxifen, oestrogen or placebo pellets, and the high and low MD biochamber tissues maintained in the murine host environment for 3 months, before the high and low MD biochamber tissues were harvested for histologic and radiographic analyses. The radiographic density of high MD tissue maintained in murine biochambers was decreased in Tamoxifen-treated mice compared to oestrogen-treated mice (p = 0.02). Tamoxifen treatment of high MD tissue in SCID mice led to a decrease in stromal (p = 0.009), and an increase in adipose (p = 0.023) percent areas, compared to placebo-treated mice. No histologic or radiographic differences were observed in low MD biochamber tissue with any treatment. High MD biochamber tissues maintained in mice implanted with Tamoxifen, oestrogen or placebo pellets had dynamic and measurable histologic compositional and radiographic changes. This further validates the dynamic nature of the MD xenograft model, and suggests the biochamber model may be useful for assessing the underlying molecular pathways of Tamoxifen-reduced MD, and in testing of other pharmacologic interventions in a preclinical model of high MD.

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Acknowledgments

This work was supported by the Victorian Breast Cancer Research Consortium (MCS, EWT, JH), the St Vincent’s Hospital Research Endowment Fund (EWT 2008, 2009), the National Health and Medical Research Council (GLC, MCS, JH) and the University of Melbourne Research Grant Support Scheme (MRGSS; EWT, IH, GLC). This study benefited from support by the Victorian Government’s Operational Infrastructure Support Program to St. Vincent’s Institute.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Surgery, St Vincent’s Hospital, University of Melbourne, Melbourne, VIC, Australia

    G. L. Chew, C. W. Huo, D. Huang, M. A. Henderson & E. W. Thompson

  2. Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia

    T. Blick & E. W. Thompson

  3. Department of Pathology, University of Melbourne, Melbourne, VIC, Australia

    P. Hill

  4. St Vincent’s BreastScreen, St Vincent’s Hospital Melbourne, University of Melbourne, Melbourne, VIC, Australia

    J. Cawson & H. Frazer

  5. School of Population Health, University of Melbourne, Melbourne, VIC, Australia

    M. C. Southey & J. L. Hopper

  6. Peter MacCallum Cancer Center, East Melbourne, VIC, Australia

    K. Britt & M. A. Henderson

  7. The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia

    K. Britt

  8. Department of Medicine, Bar Ilan University, Tel Aviv, Israel

    I. Haviv

  9. St Vincent’s Institute, Melbourne, VIC, Australia

    E. W. Thompson

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  1. G. L. Chew
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Correspondence to G. L. Chew.

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Chew, G.L., Huo, C.W., Huang, D. et al. Effects of Tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers. Breast Cancer Res Treat 148, 303–314 (2014). https://doi.org/10.1007/s10549-014-3169-2

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  • DOI: https://doi.org/10.1007/s10549-014-3169-2

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