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Dynamic changes in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers during various murine peripartum states and over time

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Abstract

Mammographic density (MD) is a strong heritable risk factor for breast cancer, and may decrease with increasing parity. However, the biomolecular basis for MD-associated breast cancer remains unclear, and systemic hormonal effects on MD-associated risk is poorly understood. This study assessed the effect of murine peripartum states on high and low MD tissue maintained in a xenograft model of human MD. Method High and low MD human breast tissues were precisely sampled under radiographic guidance from prophylactic mastectomy specimens of women. The high and low MD tissues were maintained in separate vascularised biochambers in nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum involution or lactation for three additional weeks. High and low MD biochamber material was harvested for histologic and radiographic comparisons during various murine peripartum states. High and low MD biochamber tissues in nulliparous mice were harvested at different timepoints for histologic and radiographic comparisons. Results High MD biochamber tissues had decreased stromal (p = 0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in high MD biochamber tissues during lactation. A difference in radiographic density was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004) between nulliparous, pregnant and involution groups. No differences in tissue composition were observed in high or low MD biochamber tissues maintained for different durations, although radiographic density increased over time. Conclusion High MD biochamber tissues had measurable histologic changes after postpartum involution or lactation. Alterations in radiographic density occurred in biochamber tissues between different peripartum states and over time. These findings demonstrate the dynamic nature of the human MD xenograft model, providing a platform for studying the biomolecular basis of MD-associated cancer risk.

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Acknowledgments

This work was supported by the Victorian BC Research Consortium (MCS, EWT, JH), the St Vincent’s Hospital Research Endowment Fund (EWT 2008, 2009), and National Health and Medical Research Council (GLC, MCS, JH) and the University of Melbourne Research Grant Support Scheme (MRGSS; EWT, IH, GLC). We thank Sue MacAuley and Nadine Wood (St Vincent’s BreastScreen, St Vincent’s Hospital, Victoria) for help with radiography and tissue sampling. St Vincent’s Institute receives support from the Victorian Government’s Operational Infrastructure Support Program.

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Authors and Affiliations

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

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

  2. St. Vincent’s Institute, Fitzroy, VIC, Australia

    T. Blick & E. W. Thompson

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

    P. Hill & I. Haviv

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

    J. Cawson & H. Frazer

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

    M. D. Southey & J. L. Hopper

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

    M. A. Henderson

  7. Department of Medicine, Bar Ilan University, Zfat, Israel

    I. Haviv

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

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10549_2013_2642_MOESM1_ESM.pptx

Supp Fig. 1 a) The scatter plot column graph comparing the percentage tissue area of high MD biochamber tissues harvested from pregnant and lactating mice did not demonstrate a difference between stromal and fat percentage areas. An increase in gland percentage area was observed in high MD biochamber tissues harvested from lactating compared to pregnant mice. b) The scatter plot column graph comparing the percentage tissue area of high MD biochamber tissues harvested from pregnant and postpartum involution mice did not demonstrate a difference. (PPTX 3613 kb)

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Chew, G.L., Huang, D., Huo, C.W. et al. Dynamic changes in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers during various murine peripartum states and over time. Breast Cancer Res Treat 140, 285–297 (2013). https://doi.org/10.1007/s10549-013-2642-7

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