2. Academic Validation
  3. Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study

Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study

  • Breast Cancer Res. 2025 Jan 6;27(1):2. doi: 10.1186/s13058-024-01956-w.
Zhihao Fang # 1 2,  Guohong Ren # 1 2,  Shouyu Ke # 1 2,  Qimin Xu 1 2,  Yuhua Chen 3,  Xiaoyuan Shi 4,  Cheng Guo 5 6,  Jian Huang 7 8 9 10
Affiliations

Affiliations

  • 1 Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road, Hangzhou, Zhejiang, China.
  • 2 Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 3 Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 4 Analytical Instrument Trading Co., Ltd, SCIEX, Shanghai, China.
  • 5 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. cheng_guo@zju.edu.cn.
  • 6 Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. cheng_guo@zju.edu.cn.
  • 7 Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road, Hangzhou, Zhejiang, China. drhuangjian@zju.edu.cn.
  • 8 Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. drhuangjian@zju.edu.cn.
  • 9 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. drhuangjian@zju.edu.cn.
  • 10 Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. drhuangjian@zju.edu.cn.
  • # Contributed equally.
PMID: 39762945 DOI: 10.1186/s13058-024-01956-w
Abstract

Background: Neoadjuvant chemotherapy (NACT) is the standard-of-care treatment for patients with locally advanced breast Cancer (LABC), providing crucial benefits in tumor downstaging. Clinical parameters, such as molecular subtypes, influence the therapeutic impact of NACT. Moreover, severe adverse events delay the treatment process and reduce the effectiveness of therapy. Although metabolic changes during Cancer treatment are crucial determinant factors in therapeutic responses and toxicities, related clinical research remains limited.

Methods: One hundred paired blood samples were collected from 50 patients with LABC before and after a complete NACT treatment cycle. Untargeted metabolomics was used by liquid chromatography-mass spectrometry (LC-MS) to investigate the relationship between dynamically changing metabolites in serum and the responses and toxicities of NACT.

Results: Firstly, we observed significant alterations in serum metabolite levels pre- and post-NACT, with a predominant enrichment in the sphingolipid and amino acid metabolism pathways. Second, pre-treatment serum metabolites successfully predicted the therapeutic response and hematotoxicities during NACT. In particular, molecular subtype variations in favorable treatment responses are linked to acyl carnitine levels. Finally, we discovered that the therapeutic effects of NACT could be attributed to essential amino acid metabolism.

Conclusion: This study elucidated the dynamic changes in metabolism during NACT treatment, providing a possibility for developing responsive metabolic signatures for personalized NACT treatment.

Keywords

Acylcarnitine; Breast cancer; Essential amino acid; Metabolomics; Neoadjuvant chemotherapy; Serum.

Figures
Products