Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Core Facility for Integrated Microscopy, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Breast Cancer Res. 2024 Nov 26;26(1):163. doi: 10.1186/s13058-024-01919-1.
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.
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.
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.
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.
由间质纤维胶原排列决定的组织硬度会增加乳腺癌风险并促进癌症进展。他莫昔芬是治疗受体阳性乳腺癌的标准药物，也被批准用于初级预防。我们研究了他莫昔芬及其主要代谢物对乳腺组织胶原排列的影响，以此作为硬度的替代指标，并探讨了乳腺密度（MD）与胶原排列之间的关系。
这项双盲剂量确定试验（KARISMA）的子研究纳入了 83 名健康女性，随机分配至接受为期 6 个月的 20、10、5、2.5 和 1 毫克他莫昔芬或安慰剂治疗。在治疗前后，通过超声引导的核心针乳腺活检来评估胶原排列情况，使用偏光显微镜进行评估。
他莫昔芬减少了有组织的胶原数量和整体组织排列，表现为从交联紧密的厚纤维向更细、交联程度较低的纤维转变。胶原重塑与他莫昔芬代谢物的血浆浓度相关。MD 变化与有组织胶原数量的变化无关，但与绝经前女性的交联减少相关。
在这项对健康女性的研究中，他莫昔芬降低了纤维胶原的整体排列，从而降低了乳腺组织的硬度。这些基质改变可能在他莫昔芬已确立的预防和治疗作用中发挥作用。试验注册：ClinicalTrials.gov ID：NCT03346200。于 2017 年 11 月 1 日注册。回顾性注册。
