Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast : results from the KARISMA randomised controlled trial
(2024) In Breast Cancer Research 26(1).- Abstract
Background: Tissue stiffness, dictated by organisation of interstitial fibrillar collagens, increases breast cancer risk and contributes to cancer progression. Tamoxifen is a standard treatment for receptor-positive breast cancer and is also aproved for primary prevention. We investigated the effect of tamoxifen and its main metabolites on the breast tissue collagen organisation as a proxy for stiffness and explored the relationship between mammographic density (MD) and collagen organisation. Material and methods: This sub-study of the double-blinded dose-determination trial, KARISMA, included 83 healthy women randomised to 6 months of 20, 10, 5, 2.5, and 1 mg of tamoxifen or placebo. Ultrasound-guided core-needle breast biopsies... (More)
Background: Tissue stiffness, dictated by organisation of interstitial fibrillar collagens, increases breast cancer risk and contributes to cancer progression. Tamoxifen is a standard treatment for receptor-positive breast cancer and is also aproved for primary prevention. We investigated the effect of tamoxifen and its main metabolites on the breast tissue collagen organisation as a proxy for stiffness and explored the relationship between mammographic density (MD) and collagen organisation. Material and methods: This sub-study of the double-blinded dose-determination trial, KARISMA, included 83 healthy women randomised to 6 months of 20, 10, 5, 2.5, and 1 mg of tamoxifen or placebo. Ultrasound-guided core-needle breast biopsies collected before and after treatment were evaluated for collagen organisation by polarised light microscopy. Results: Tamoxifen reduced the amount of organised collagen and overall organisation, reflected by a shift from heavily crosslinked thick fibres to thinner, less crosslinked fibres. Collagen remodelling correlated with plasma concentrations of tamoxifen metabolites. MD change was not associated with changes in amount of organised collagen but was correlated with less crosslinking in premenopausal women. Conclusions: In this study of healthy women, tamoxifen decreased the overall organisation of fibrillar collagens, and consequently, the breast tissue stiffness. These stromal alterations may play a role in the well-established preventive and therapeutic effects of tamoxifen. Trial registration ClinicalTrials.gov ID: NCT03346200. Registered November 1st, 2017. Retrospectively registered.
(Less)
- author
- organization
- publishing date
- 2024-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Breast Cancer Research
- volume
- 26
- issue
- 1
- article number
- 163
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85210452490
- pmid:39593191
- ISSN
- 1465-5411
- DOI
- 10.1186/s13058-024-01919-1
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2024.
- id
- fb040e11-d251-470d-9bde-d500ce66d274
- date added to LUP
- 2024-12-07 18:57:00
- date last changed
- 2025-07-06 12:13:12
@article{fb040e11-d251-470d-9bde-d500ce66d274,
abstract = {{<p>Background: Tissue stiffness, dictated by organisation of interstitial fibrillar collagens, increases breast cancer risk and contributes to cancer progression. Tamoxifen is a standard treatment for receptor-positive breast cancer and is also aproved for primary prevention. We investigated the effect of tamoxifen and its main metabolites on the breast tissue collagen organisation as a proxy for stiffness and explored the relationship between mammographic density (MD) and collagen organisation. Material and methods: This sub-study of the double-blinded dose-determination trial, KARISMA, included 83 healthy women randomised to 6 months of 20, 10, 5, 2.5, and 1 mg of tamoxifen or placebo. Ultrasound-guided core-needle breast biopsies collected before and after treatment were evaluated for collagen organisation by polarised light microscopy. Results: Tamoxifen reduced the amount of organised collagen and overall organisation, reflected by a shift from heavily crosslinked thick fibres to thinner, less crosslinked fibres. Collagen remodelling correlated with plasma concentrations of tamoxifen metabolites. MD change was not associated with changes in amount of organised collagen but was correlated with less crosslinking in premenopausal women. Conclusions: In this study of healthy women, tamoxifen decreased the overall organisation of fibrillar collagens, and consequently, the breast tissue stiffness. These stromal alterations may play a role in the well-established preventive and therapeutic effects of tamoxifen. Trial registration ClinicalTrials.gov ID: NCT03346200. Registered November 1st, 2017. Retrospectively registered.</p>}},
author = {{Göransson, Sara and Hernández-Varas, Pablo and Hammarström, Mattias and Hellgren, Roxanna and Bäcklund, Magnus and Lång, Kristina and Rosendahl, Ann H. and Eriksson, Mikael and Borgquist, Signe and Strömblad, Staffan and Czene, Kamila and Hall, Per and Gabrielson, Marike}},
issn = {{1465-5411}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Breast Cancer Research}},
title = {{Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast : results from the KARISMA randomised controlled trial}},
url = {{http://dx.doi.org/10.1186/s13058-024-01919-1}},
doi = {{10.1186/s13058-024-01919-1}},
volume = {{26}},
year = {{2024}},
}