Abstract
Mammographic density (MD) adjusted for age and body mass index (BMI) is a strong heritable breast cancer risk factor; however, its biological basis remains elusive. Previous studies assessed MD-associated histology using random sampling approaches, despite evidence that high and low MD areas exist within a breast and are negatively correlated with respect to one another. We have used an image-guided approach to sample high and low MD tissues from within individual breasts to examine the relationship between histology and degree of MD. Image-guided sampling was performed using two different methodologies on mastectomy tissues (n = 12): (1) sampling of high and low MD regions within a slice guided by bright (high MD) and dark (low MD) areas in a slice X-ray film; (2) sampling of high and low MD regions within a whole breast using a stereotactically guided vacuum-assisted core biopsy technique. Pairwise analysis accounting for potential confounders (i.e. age, BMI, menopausal status, etc.) provides appropriate power for analysis despite the small sample size. High MD tissues had higher stromal (P = 0.002) and lower fat (P = 0.002) compositions, but no evidence of difference in glandular areas (P = 0.084) compared to low MD tissues from the same breast. High MD regions had higher relative gland counts (P = 0.023), and a preponderance of Type I lobules in high MD compared to low MD regions was observed in 58% of subjects (n = 7), but did not achieve significance. These findings clarify the histologic nature of high MD tissue and support hypotheses regarding the biophysical impact of dense connective tissue on mammary malignancy. They also provide important terms of reference for ongoing analyses of the underlying genetics of MD.
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Acknowledgments
This work 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), National Health and Medical Research Council (MCS, JH, IGC) and the Agency for Science Technology and Research (A*STAR) (NSS-PhD award to SJL). We thank Sue MacAuley, Zara Werts and Nadine Wood (St Vincent’s BreastScreen, St. Vincent’s Hospital, Victoria) for help with radiography and tissue sampling; Dyan Chitty (The University of Melbourne) and Annabel Southey (St. Vincent’s Institute) for help with histological counts; Tony Blick and Dexing Huang (St. Vincent’s Institute) for help with tissue accrual and Faxitron imaging; The Victorian Cancer Biobank and Samantha Boyle (Peter MacCallum Cancer Centre) for help with tissue accrual; Kevin Nguyen and Jacob Fry (The University of Melbourne) for help with X-ray film digitisation; Joshy George (Peter MacCallum Cancer Centre) for statistical consultation; Lilian Soon (University of Sydney) for early histological analysis; Tina Cardamone and Louise Pontell (The Australian Phenomics Network, The University of Melbourne) for help with slide scanning.
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Ian G. Campbell and Erik W. Thompson shared senior authorship.
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Lin, S.J., Cawson, J., Hill, P. et al. Image-guided sampling reveals increased stroma and lower glandular complexity in mammographically dense breast tissue. Breast Cancer Res Treat 128, 505–516 (2011). https://doi.org/10.1007/s10549-011-1346-0
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DOI: https://doi.org/10.1007/s10549-011-1346-0