title: Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues.
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.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden. marike.gabrielson@ki.se.
authors.forename: Marike
authors.initials: M
authors.lastname: Gabrielson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden.
authors.forename: Flaminia
authors.initials: F
authors.lastname: Chiesa
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Z1:00, 171 76, Stockholm, Sweden.
authors.forename: Janna
authors.initials: J
authors.lastname: Paulsson
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Z1:00, 171 76, Stockholm, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Strell
authors.affiliation: Department of Mammography, Unilabs, Jan Waldenströms gata 22, 205 02, Malmö, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Behmer
authors.affiliation: Department of Mammography, Unilabs, Hospital of Helsingborg, 251 87, Helsingborg, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Rönnow
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden.
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Z1:00, 171 76, Stockholm, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Östman
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Hall
mesh_terms: D000328:Adult; D000368:Aged; D062005:Biopsy, Large-Core Needle; D001940:Breast / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D000071060:Breast Density; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008327:Mammography / Q000379:methods*; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*; D016217:Ultrasonography, Mammary
chemical_list: D011960:Receptors, Estrogen
keywords: Breast cancer; Breast tissue; Histology; Hormone receptor status; Mammographic density; Stromal breast tissue