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High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers

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Abstract

Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.

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Acknowledgments

This study was supported by the Victorian Breast Cancer Research Consortium (MCS, IGC, EWT, JH), the St Vincent’s Hospital Research Endowment Fund (EWT, JC, PH 2008, 2009), and National Health and Medical Research Council (GLC, MCS, JH, IGC). SJL is supported by the NSS-PhD scholarship from the Agency for Science, Technology, and Research (A*STAR). St Vincent’s Institute and The O’Brien Institute receive infrastructure funding from the Victorian State Government under the Medical Research Operational Infrastructure program. We thank Sue MacAuley and Nadine Wood (St Vincent’s BreastScreen, St Vincent’s Hospital, Victoria) for help with radiography and tissue sampling; The Victorian Cancer Biobank (Peter MacCallum Cancer Centre) for help with tissue accrual; The Department of Pathology, St Vincent’s Hospital Melbourne, for assistance with tissue processing and immunohistochemical staining on the autostainer.

Conflict of interests

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Authors and Affiliations

  1. Department of Surgery, St Vincent’s Hospital, The University of Melbourne, Fitzroy, Melbourne, VIC, 3065, Australia

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

  2. St Vincent’s Institute, 29 Regent St., Fitzroy, Melbourne, VIC, 3065, Australia

    D. Huang, T. Blick & E. W. Thompson

  3. Peter MacCallum Cancer Center, East Melbourne, VIC, 3002, Australia

    S. J. Lin, M. A. Henderson & I. G. Campbell

  4. Department of Pathology, The University of Melbourne, Parkville, Melbourne, VIC, 3010, Australia

    S. J. Lin, P. Hill & M. C. Southey

  5. St Vincent’s Pathology, Fitzroy, Melbourne, VIC, 3065, Australia

    P. Hill

  6. St Vincent’s BreastScreen, St Vincent’s Hospital Campus, The University of Melbourne, Fitzroy, Melbourne, VIC, 3065, Australia

    J. Cawson

  7. O’Brien Institute of Microsurgery, Fitzroy, Melbourne, VIC, 3065, Australia

    W. A. Morrison

  8. Centre for M.E.G.A., The University of Melbourne, Parkville, Melbourne, VIC, 3010, Australia

    J. L. Hopper

  9. Faculty of Medicine, Bar Ilan University, Zfat, Israel

    I. Haviv

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  1. G. L. Chew
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  2. D. Huang
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  4. C. Huo
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  5. T. Blick
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  7. P. Hill
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  9. W. A. Morrison
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  10. I. G. Campbell
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  13. I. Haviv
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  14. E. W. Thompson
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Correspondence to G. L. Chew.

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Chew, G.L., Huang, D., Lin, S.J. et al. High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers. Breast Cancer Res Treat 135, 177–187 (2012). https://doi.org/10.1007/s10549-012-2128-z

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  • DOI: https://doi.org/10.1007/s10549-012-2128-z

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