Effects of tamoxifen on normal breast tissue histological composition : Results from a randomised six-arm placebo-controlled trial in healthy women

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Effects of tamoxifen on normal breast tissue histological composition : Results from a randomised six-arm placebo-controlled trial in healthy women

Gabrielson, Marike (author): Karolinska Institutet,Karolinska Institute

Hammarström, Mattias (author): Karolinska Institutet,Karolinska Institute

Bäcklund, Magnus (author): Karolinska Institutet,Karolinska Institute

Bergqvist, Jenny (author): Karolinska Institutet,Karolinska Institute

Lång, Kristina (author): Lund 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

Rosendahl, Ann H. (author): 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

Borgquist, Signe (author): 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,Aarhus University Hospital,Skåne University Hospital

Hellgren, Roxanna (author): Stockholm South General Hospital

Czene, Kamila (author): Karolinska Institutet,Karolinska Institute

Hall, Per (author): Karolinska Institutet,Karolinska Institute,Stockholm South General Hospital

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2023-01-22
2023
English.
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 152:11, s. 2362-2372

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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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By the author/editor: Gabrielson, Mari ...; Hammarström, Mat ...; Bäcklund, Magnus; Bergqvist, Jenny; Lång, Kristina; Rosendahl, Ann H ...; show more...; Borgquist, Signe; Hellgren, Roxann ...; Czene, Kamila; Hall, Per; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

Articles in the publication: International Jo ...

By the university: Lund University; Karolinska Institutet

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Effects of tamoxifen on normal breast tissue histological composition : Results from a randomised six-arm placebo-controlled trial in healthy women

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