Poster Presentations
Explant Model of the Normal Human Breast Mimics Tamoxifen Clinical Trial Results
Poster Presentation at Basel Breast Consortium (BBC)
Author and Presenter:
Anthony J. Wilby
Abstract:
Tamoxifen, an anti-oestrogen, is the only licensed medication in the UK for breast cancer prevention in high-risk, pre-menopausal women. Data from the Biomarkers of Breast Cancer Prevention (BBCP) trial show that, while tamoxifen reduces overall proliferation after three months of treatment, a subset of women (5/13) show stable or increased proliferation. As proliferation is used as a surrogate marker for risk reduction, understanding mechanisms behind this differential response and any links to therapeutic resistance, as well as identifying potential alternative therapies, is essential. New drugs need first to be tested preclinically, but this is hindered by the lack of suitable models: cell lines lack oestrogen receptor expression, while patient-derived organoids and mammospheres lack human ECM components and cell–cell interactions. To address this, we developed a preclinical explant model using breast tissue from high-risk women undergoing risk-reducing mastectomies. This model uniquely preserves 3D architecture, proliferation, immune cell prevalence, and hormone receptor expression and responsiveness—features absent in existing systems. Testing tamoxifen in the explant model yielded results similar to those from the BBCP trial, showing an overall reduction in proliferation (Ki67) but stable or increased proliferation in 4 out of 9 women. Future work will further validate the explant model using matched BBCP patient samples, providing a platform to interrogate the biological drivers of resistance and response, identify new targeting opportunities, and drive personalized prevention strategies.
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