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Mammographic breast density and the expression of androgen receptor, caspase 3, Ki67 and proteoglycans in pre-menopausal women.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
Institutionen för Kvinnors och Barns hälsa, Karolinska Institutet, Solna.
Institutionen för Kvinnors och Barns hälsa, Karolinska Institutet, Solna.
Institutionen för Kvinnors och Barns hälsa, Karolinska Institutet, Solna.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]



Background: Mammographic breast density (BD) is a strong risk factor for breast cancer, but underlying histopathological correlates are not fully understood. In the human breast the main part of the volume constitutes of stroma. We examined the correlation between BD and Ki67, caspase 3, androgen receptor (AR), syndecan-1 , syndecan –4 and decorin in pre-menopausal non cancerous breast tissue.

Method: Pre-menopausal women (n = 55), planned for a reduction mammoplasty and having a breast sample (needle biopsy) at the same time of preoperative mammography, were included. Protein levels of the proteoglycans syndecan-1, syndecan-4, decorin and the AR, Ki67 and caspase 3, were examined by immunohistochemistry (IHC) and gene expression by real-time RT-PCR. Results were compared with regard to BD class (< 20% vs. > 40%) and mean BD (%), using non-parametric analysis and adjustments. 

Results: BD (%) decreased significantly with age (p < 0.0001) and with BMI (p = 0.002) but was similar in the follicular and luteal phases. The AR gene expression increased significantly with increasing BD class and with mean BD% (rs = 0.43; p = 0.048, for both), and was strengthened after adjustment for age. After adjustment for age, caspace 3 was positively associated with mean BD (%), with borderline significance (0.55; 0.053), whereas IHC was negatively associated to BD class (-0.61; 0.026). PCR values for Ki67, syndecan-1 and syndecan-4 were numerically higher in dense breasts (p > 0.05 for all).

Conclusion: In pre-menopausal women, gene expression for AR and caspase 3 increased, whereas protein levels of caspase 3 might decrease, with increasing breast density. This limited study showed no significant associations between Ki67, syndecans, decorin and breast density.


Keyword [en]
mammographic breast density, proteoglycans, premenopausal
Research subject
Obstetrics and Gynaecology
URN: urn:nbn:se:uu:diva-147784OAI: oai:DiVA.org:uu-147784DiVA: diva2:400837
Available from: 2011-02-28 Created: 2011-02-28 Last updated: 2011-05-04
In thesis
1. Effects of Endogenous and Exogenous Hormones on the Female Breast: With Special Reference to the Expression of Proteoglycans
Open this publication in new window or tab >>Effects of Endogenous and Exogenous Hormones on the Female Breast: With Special Reference to the Expression of Proteoglycans
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis aims to study the effects of endogenous and exogenous hormones and mammographic breast density (BD) on cellular markers in non-cancerous female breast tissue. Women on the waiting list for breast reduction plastic surgery were recruited (n = 79), and randomized to 2 months of hormone therapy or no therapy before surgery. The women had a mammogram and a needle biopsy 2 months before surgery and tissue samples were obtained at the operation.

In premenopausal women, estrogen receptor (ER)α levels were associated with age (p = 0.0002), were similar in the follicular and luteal phases of the menstrual cycle and were higher in parous than in nulliparous women (p = 0.009). Current smokers had lower PR levels than non-smokers (p = 0.019). Women on oral contraception had lower ERα (p = 0.048) and PR (p = 0.007) levels than women in the follicular phase. The ERα levels did not differ significantly between postmenopausal estrogen and estrogen-progestogen users, but PR levels were lower among estrogen-progestogen users (p = 0.03).

We found lower expression of the genes for decorin and syndecans 1 and 4 in the luteal phase than in the follicular phase, among parous women. Protein levels of the androgen receptor, syndecan-4 and decorin was lower in premenopausal women who were using oral contraceptives (OC) than in those in the follicular phase (p = 0.002 - 0.02), whereas no significant differences between OC use and the luteal phase were found.

In premenopausal women, BD was negatively associated with age and body mass index but was similar for the menstrual phases. Breast density was associated with genetic expression of the androgen receptor and remained significant after adjustment for age (rs = 0.56; p = 0.04). After adjustement for age, breast density was also marginally associated with expression of the caspase 3 gene (0.55; 0.053). However, protein levels of caspase 3 was negatively associated (-0.61; 0.03).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 76 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 651
breast tissue, proteoglycans, mammographic density, oral contraceptives, androgen receptor, proliferation, apoptosis, extracellular matrix, premenopausal
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
urn:nbn:se:uu:diva-147793 (URN)978-91-554-8018-9 (ISBN)
Public defence
2011-04-14, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (Swedish)
Available from: 2011-03-23 Created: 2011-02-28 Last updated: 2011-05-04Bibliographically approved

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