Multiomic integration reveals subtype-specific predictors of neoadjuvant treatment response in breast cancer.

Journal: Science advances
Published Date: Jul 4, 2025

Abstract

Neoadjuvant therapy has been widely used in breast cancer, but treatment response varies among individuals. We conducted multiomic profiling on tumor samples from 149 Chinese patients with breast cancer across ERHER2, ERHER2, and ERHER2 subtypes, categorizing outcomes as pathologic complete response (pCR;  = 81) or residual disease (RD;  = 68). We identified distinct molecular features linked to pCR in each subtype: elevated cell proliferation in patients with ERHER2 pCR, higher methylation in patients with ERHER2 RD, increased methylation in patients with ERHER2 RD, and hypermethylation in patients with ERHER2 RD. These findings were subsequently validated in independent datasets. By integrating clinical and multiomic data, we developed MOPCR, a subtype-specific machine learning model that outperformed single-omic approaches in predicting treatment response. MOPCR demonstrated potential generalizability across cohorts and provided preliminary stratification of patient subgroups with higher pCR probability, offering valuable insights for precision cancer management.

Authors

  • Zongchao Mo
    Division of Life Science, Department of Chemical and Biological Engineering, and State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Hong Kong, SAR, China.
  • Mei Yang
    Department of Geriatric Cardiology; National Center for Clinical Research of Geriatric Diseases, Xiangya Hospital, Central South University, Changsha 410008, China.
  • Zhihan Zhu
    Division of Life Science, Department of Chemical and Biological Engineering, and State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Hong Kong, SAR, China.
  • Minghao Wang
    Key Laboratory of Geographic Information Science, Ministry of Education, East China Normal University, Shanghai, 200241, China; School of Geographic Sciences, East China Normal University, Shanghai, 200241, China; Key Laboratory of Spatial-temporal Big Data Analysis and Application of Natural Resources in Megacities, Ministry of Natural Resources, Shanghai, 200241, China.
  • Haoyu Wang
    North Carolina State University, Department of Statistics, Raleigh, North Carolina, USA.
  • Zhanye Zhang
    Division of Life Science, Department of Chemical and Biological Engineering, and State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Hong Kong, SAR, China.
  • Shanshan Lyu
    Department of Pathology, Guangdong Provincial People's Hospital, Guangzhou, 510080, China.
  • FangPing Xu
    Department of Pathology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
  • Haixia Shang
    Division of Life Science, Department of Chemical and Biological Engineering, and State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Hong Kong, SAR, China.
  • Huan Lin
    Department of Radiology, Zhujiang Hospital of Southern Medical University, No. 253, Gong Ye Da Dao Zhong, Guangzhou, Guangdong, 510280, People's Republic of China.
  • Zeyan Xu
    School of Medicine, South China University of Technology, Guangzhou 510006, China.
  • Suyun Li
    Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Xiaobo Chen
    Department of Radiology and BRIC, University of North Carolina at Chapel Hill, Chapel Hill, USA.
  • Kun Wang
    CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
  • Changhong Liang
    Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, China.
  • Jiguang Wang
    Department of Systems Biology, Columbia University, New York, NY 10032 USA.
  • Zaiyi Liu
    Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

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