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Effects of tamoxife...
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Gabrielson, MarikeKarolinska Institutet,Karolinska Institute
(author)
Effects of tamoxifen on normal breast tissue histological composition : Results from a randomised six-arm placebo-controlled trial in healthy women
- Article/chapterEnglish2023
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Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:909275b7-1f48-41d1-8577-b50e9fe274d5
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https://lup.lub.lu.se/record/909275b7-1f48-41d1-8577-b50e9fe274d5URI
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https://doi.org/10.1002/ijc.34430DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:151824257URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.
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Hammarström, MattiasKarolinska Institutet,Karolinska Institute
(author)
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Bäcklund, MagnusKarolinska Institutet,Karolinska Institute
(author)
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Bergqvist, JennyKarolinska Institutet,Karolinska Institute
(author)
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Lång, KristinaLund University,Lunds universitet,Diagnostisk radiologi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Radiology Diagnostics, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)med-ksd
(author)
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Rosendahl, Ann H.Karolinska Institutet,Lund University,Lunds universitet,Bröstcancer - prevention & intervention,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breast cancer prevention & intervention,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital(Swepub:lu)onk-aro
(author)
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Borgquist, SigneLund University,Lunds universitet,Bröstcancer - prevention & intervention,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breast cancer prevention & intervention,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Aarhus University Hospital,Skåne University Hospital(Swepub:lu)ront-sbo
(author)
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Hellgren, RoxannaStockholm South General Hospital
(author)
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Czene, KamilaKarolinska Institutet,Karolinska Institute
(author)
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Hall, PerKarolinska Institutet,Karolinska Institute,Stockholm South General Hospital(Swepub:lu)pe3137ha
(author)
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Karolinska InstitutetKarolinska Institute
(creator_code:org_t)
Related titles
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In:International Journal of Cancer: Wiley152:11, s. 2362-23720020-71361097-0215
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Gabrielson, Mari ...
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Hammarström, Mat ...
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Bäcklund, Magnus
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Bergqvist, Jenny
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Lång, Kristina
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Rosendahl, Ann H ...
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Borgquist, Signe
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Hellgren, Roxann ...
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Czene, Kamila
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Hall, Per
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