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Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues

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Abstract

Following female sex and age, mammographic density is considered one of the strongest risk factors for breast cancer. Despite the association between mammographic density and breast cancer risk, little is known about the underlying histology and biological basis of breast density. To better understand the mechanisms behind mammographic density we assessed morphology, proliferation and hormone receptor status in relation to mammographic density in breast tissues from healthy women. Tissues were obtained from 2012–2013 by ultrasound-guided core needle biopsy from 160 women as part of the Karma (Karolinska mammography project for risk prediction for breast cancer) project. Mammograms were collected through routine mammography screening and mammographic density was calculated using STRATUS. The histological composition, epithelial and stromal proliferation status and hormone receptor status were assessed through immunohistochemical staining. Higher mammographic density was significantly associated with a greater proportion of stromal and epithelial tissue and a lower proportion of adipose tissue. Epithelial expression levels of Ki-67, oestrogen receptor (ER) and progesterone receptor (PR) were not associated with mammographic density. Epithelial Ki-67 was associated with a greater proportion of epithelial tissue, and epithelial PR was associated with a greater proportion of stromal and a lower proportion of adipose tissue. Epithelial ER was not associated with any tissues. In contrast, expression of ER in the stroma was significantly associated with a greater proportion of stroma, and negatively associated with the amount of adipose tissue. High mammographic density is associated with higher amount of stroma and epithelium and less amount of fat, but is not associated with a change in epithelial proliferation or receptor status. Increased expressions of both epithelial PR and stromal ER are associated with a greater proportion of stroma, suggesting hormonal involvement in regulating breast tissue composition.

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Abbreviations

BMI:

Body mass index

ER:

Oestrogen receptor

HRT:

Hormone replacement therapy

IHC:

Immunohistochemical

Karma:

Karolinska mammography project for risk prediction for breast cancer

PR:

Progesterone receptor

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Acknowledgments

The authors thank the Märit and Hans Rausings Initiative Against Breast Cancer, the Swedish Research Council and the Kamprad Family Foundation for Entrepreneurship, Research & Charity. Giovanni Galvis Rojas is acknowledged for contributions during the initiation of this project.

Author’s contributions

MG drafted the manuscript, contributed to the study design and carried out the majority of the histological data analyses and postimaging analyses. FC provided critical statistical support, helped to interpret the corresponding data and revised the manuscript. JP, CS, CB and KR all critically participated in collection of tissue samples and histological preparation of tissues. KC helped to conceive of the study design, interpreted data and revised the manuscript. AÖ helped to conceive of the study and revised the manuscript. PH conceived of the study, participated in study design and data interpretation and helped to draft the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden

    Marike Gabrielson, Flaminia Chiesa, Kamila Czene & Per Hall

  2. Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Z1:00, 171 76, Stockholm, Sweden

    Janna Paulsson, Carina Strell & Arne Östman

  3. Department of Mammography, Unilabs, Jan Waldenströms gata 22, 205 02, Malmö, Sweden

    Catharina Behmer

  4. Department of Mammography, Unilabs, Hospital of Helsingborg, 251 87, Helsingborg, Sweden

    Katarina Rönnow

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  1. Marike Gabrielson
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Correspondence to Marike Gabrielson.

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Gabrielson, M., Chiesa, F., Paulsson, J. et al. Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues. Breast Cancer Res Treat 158, 253–261 (2016). https://doi.org/10.1007/s10549-016-3877-x

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