Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial
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 th...
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2024-11-01
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| Series: | Breast Cancer Research |
| Online Access: | https://doi.org/10.1186/s13058-024-01919-1 |
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| author | Sara Göransson Pablo Hernández-Varas Mattias Hammarström Roxanna Hellgren Magnus Bäcklund Kristina Lång Ann H. Rosendahl Mikael Eriksson Signe Borgquist Staffan Strömblad Kamila Czene Per Hall Marike Gabrielson |
| author_facet | Sara Göransson Pablo Hernández-Varas Mattias Hammarström Roxanna Hellgren Magnus Bäcklund Kristina Lång Ann H. Rosendahl Mikael Eriksson Signe Borgquist Staffan Strömblad Kamila Czene Per Hall Marike Gabrielson |
| author_sort | Sara Göransson |
| collection | DOAJ |
| description | 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 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. |
| format | Article |
| id | doaj-art-40c146f1bcb84f65bc0a63a82feffc1a |
| institution | Kabale University |
| issn | 1465-542X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-40c146f1bcb84f65bc0a63a82feffc1a2024-12-01T12:51:28ZengBMCBreast Cancer Research1465-542X2024-11-0126111110.1186/s13058-024-01919-1Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trialSara Göransson0Pablo Hernández-Varas1Mattias Hammarström2Roxanna Hellgren3Magnus Bäcklund4Kristina Lång5Ann H. Rosendahl6Mikael Eriksson7Signe Borgquist8Staffan Strömblad9Kamila Czene10Per Hall11Marike Gabrielson12Department of Biosciences and Nutrition, Karolinska InstitutetCore Facility for Integrated Microscopy, Department of Biomedical Sciences, Faculty of Health Sciences, University of CopenhagenDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Breast ImagingDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Translational Medicine, Diagnostic Radiology, Lund UniversityDepartment of Clinical Sciences Lund, Oncology, Lund University and Skåne University HospitalDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Oncology, Aarhus University Hospital, Aarhus UniversityDepartment of Biosciences and Nutrition, Karolinska InstitutetDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetAbstract 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.https://doi.org/10.1186/s13058-024-01919-1 |
| spellingShingle | Sara Göransson Pablo Hernández-Varas Mattias Hammarström Roxanna Hellgren Magnus Bäcklund Kristina Lång Ann H. Rosendahl Mikael Eriksson Signe Borgquist Staffan Strömblad Kamila Czene Per Hall Marike Gabrielson Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial 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 |
| title_full | Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial |
| title_fullStr | Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial |
| title_full_unstemmed | Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial |
| title_short | Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial |
| title_sort | low dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast results from the karisma randomised controlled trial |
| url | https://doi.org/10.1186/s13058-024-01919-1 |
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