Abstract LT01: Spatial Phenotypes Ascribed to Cancers with Extreme Resistance (SPACER) in HR+ HER2- Metastatic Breast Cancer – a Multi-Institutional Use-Case Study of the Translational Research Integration and Support Platform by the Singapore Transl

Abstract Background & Objectives: Despite advances in breast cancer treatment, there remains a critical need for reliable predictive biomarkers to guide treatment selection for hormone receptor positive (HR+) breast cancer. To address this gap, we conducted a retrospective study examining HR+HER2- metastatic breast cancer (MBC) patients who showed either exceptional response (time to progression, TTP ≥ 30 months) or resistance (TTP ≤ 6 months) to cyclin dependent kinase 4/6 inhibitors (CDK4/6i). To broaden the study impact, we established a multi-institutional collaboration across Singapore's major public health clusters, encompassing the National University Hospital (NUH), National Cancer Center Singapore (NCCS), and Tan Tock Seng Hospital (TTSH). This was achieved though the Spatial Phenotypes Ascribed to Cancers with Extreme Resistance (SPACER) initiative under the Singapore Translational Cancer Consortium (STCC). Methods: Utilizing STCC's Translational and Pre-clinical Research Pipeline, we identified a nationwide, cross-cluster cohort of 100 cases comprising both responders and non-responders to CDK4/6i therapy. We conducted comprehensive molecular profiling of pre-treatment archival histopathological specimens using state-of-the-art spatial genomic and proteomic technologies available locally. These included 10x Xenium spatial transcriptomics, Lunaphore COMET and Akoya Phenocycler Fusion hyperplex immunohistochemistry, enabling spatially resolved and in situ single-cell level analysis of CDK4/6i treatment response predictors. Results: We developed study-specific spatial analytical pipelines to characterise both resistance-associated expression signatures in tumour cells and immune signatures within the tumour microenvironment. This extensive molecular data repository will serve as a valuable resource for further developing biomarkers and predictive models, with potential implications for improving cancer management, optimising healthcare expenditure, and enhancing cancer outcomes both locally and globally. Conclusions: The SPACER HR+HER2- metastatic breast cancer study demonstrates a successful large-scale clinical research collaboration across Singapore's public healthcare institutions (NUH, NCCS, TTSH). STCC, a national cancer consortium, serves as a comprehensive platform facilitating coordinated translational cancer research, addressing the need for synergised research efforts across Singapore's healthcare landscape. Citation Format: Michał Marek Hoppe, Qing Hao Miow, Yu Hui Cheng, Carmen Yu Fei Yuen, Nimmi Baby, Zhen Wei Neo, Li Yen Chong, Yanfen Peng, Kah Weng Lau, Bernard Chi Shern Ho, Timothy Kwang Yong Tay, Jia Li Low, Lavina Bharwani, Joe Poh Sheng Yeong, Jaynes Patrick William, Alexander Lezhava, Jason Yong Sheng Chan, Anand Devaprasath Jeyasekharan, Joline Si Jing Lim, Matilda Xin Wei Lee, Valerie Yue Ming Heong, Tira Jing Ying Tan. LT01: Spatial Phenotypes Ascribed to Cancers with Extreme Resistance (SPACER) in HR+ HER2- Metastatic Breast Cancer – a Multi-Institutional Use-Case Study of the Translational Research Integration and Support Platform by the Singapore Translational Cancer Consortium (STCC) [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr LT01.