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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 ; Hammarström, Mattias ; Bäcklund, Magnus ; Bergqvist, Jenny ; Lång, Kristina LU ; Rosendahl, Ann H. LU ; Borgquist, Signe LU ; Hellgren, Roxanna ; Czene, Kamila and Hall, Per LU (2023) In International Journal of Cancer 152(11). p.2362-2372
Abstract

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... (More)

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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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
breast cancer, mammographic breast density, primary prevention, tamoxifen
in
International Journal of Cancer
volume
152
issue
11
pages
2362 - 2372
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:36637153
  • scopus:85146978968
ISSN
0020-7136
DOI
10.1002/ijc.34430
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
id
909275b7-1f48-41d1-8577-b50e9fe274d5
date added to LUP
2023-02-08 16:09:55
date last changed
2024-06-10 00:09:31
@article{909275b7-1f48-41d1-8577-b50e9fe274d5,
  abstract     = {{<p>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.</p>}},
  author       = {{Gabrielson, Marike and Hammarström, Mattias and Bäcklund, Magnus and Bergqvist, Jenny and Lång, Kristina and Rosendahl, Ann H. and Borgquist, Signe and Hellgren, Roxanna and Czene, Kamila and Hall, Per}},
  issn         = {{0020-7136}},
  keywords     = {{breast cancer; mammographic breast density; primary prevention; tamoxifen}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2362--2372}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{Effects of tamoxifen on normal breast tissue histological composition : Results from a randomised six-arm placebo-controlled trial in healthy women}},
  url          = {{http://dx.doi.org/10.1002/ijc.34430}},
  doi          = {{10.1002/ijc.34430}},
  volume       = {{152}},
  year         = {{2023}},
}