연구성과 홍보

Cell Rep Med. 2025 Jun 17;6(6):102164.

Title : Spatial and genomic profiling of residual breast cancer after neoadjuvant chemotherapy unveil divergent fates for each breast cancer subtype

Authors : Eun Seop Seo1, Sabin Park2, Eun Yoon Cho3, Jeong Eon Lee4, Hae Hyun Jung5, Jiyeon Hyeon6, Sepil An7, Seok Won Kim8, Junghoon Shin6, Jin Seok Ahn9, Yeon Hee Park9, Young-Hyuck Im10, Hoon Kim11*, Semin Lee12*, Woong-Yang Park13*, Ji-Yeon Kim14*

Affiliations :

1Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology, Seoul 06355, Republic of Korea; Geninus Inc., Seoul 05836, Republic of Korea.

2Department of Biomedical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.

3Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

4Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Seoul 06355, Republic of Korea.

5Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Republic of Korea.

6Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

7Department of Biopharmaceutical Convergence, School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, Republic of Korea.

8Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

9Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Seoul 06355, Republic of Korea; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

10Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Seoul 06355, Republic of Korea; Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Republic of Korea; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

11Department of Biopharmaceutical Convergence, School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, Republic of Korea; Department of Biohealth Regulatory Science, School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, Republic of Korea; Epigenome Dynamics Control Research Center, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, Republic of Korea.

12Department of Biomedical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.

13Geninus Inc., Seoul 05836, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Seoul 06355, Republic of Korea; Translational Genomics Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea.

14Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology, Seoul 06355, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Seoul 06355, Republic of Korea; Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Republic of Korea; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

DOI: 10.1016/j.xcrm.2025.102164

Abstract :

Residual cancer burden (RCB) is a strong prognostic marker after neoadjuvant chemotherapy (NAC) in breast cancer (BC), yet some BCs defy their predicted outcomes. Using single-cell spatial transcriptomics and genomic profiling, we investigate mechanisms underlying divergent fates of BCs with high RCB across subtypes. In triple-negative BC (TNBC), CXCL9+ macrophage-CD8+ T cell interactions via chemokines and interferon-gamma signaling promote favorable outcomes, while SPP1+ macrophage-cancer cell interactions driven by hypoxia signaling correlate with poor prognosis. In non-TNBC, the extent of basal-like cancer cells and their proximity to scarce immune cells are linked to prognosis. Additionally, tumor-intrinsic features-such as homologous recombination deficiency in hormone receptor (HR)-positive cancers and structural variations, including extrachromosomal ERBB2 DNA in human epidermal growth factor receptor 2 (HER2)-positive cancers-predict worse outcomes. This study highlights distinct genomic and microenvironmental strategies governing BC subtype-specific fates after NAC.