Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study
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...
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2025-01-01
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| Series: | Breast Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13058-024-01956-w |
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| author | Zhihao Fang Guohong Ren Shouyu Ke Qimin Xu Yuhua Chen Xiaoyuan Shi Cheng Guo Jian Huang |
| author_facet | Zhihao Fang Guohong Ren Shouyu Ke Qimin Xu Yuhua Chen Xiaoyuan Shi Cheng Guo Jian Huang |
| author_sort | Zhihao Fang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bd71190b1aac41b88d4afd62c6a91fc1 |
| institution | Kabale University |
| issn | 1465-542X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-bd71190b1aac41b88d4afd62c6a91fc12025-01-12T12:45:30ZengBMCBreast Cancer Research1465-542X2025-01-0127111510.1186/s13058-024-01956-wSerum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal studyZhihao Fang0Guohong Ren1Shouyu Ke2Qimin Xu3Yuhua Chen4Xiaoyuan Shi5Cheng Guo6Jian Huang7Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of MedicineAnalytical Instrument Trading Co., Ltd, SCIEXCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of MedicineAbstract 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.https://doi.org/10.1186/s13058-024-01956-wBreast cancerNeoadjuvant chemotherapySerumMetabolomicsAcylcarnitineEssential amino acid |
| spellingShingle | Zhihao Fang Guohong Ren Shouyu Ke Qimin Xu Yuhua Chen Xiaoyuan Shi Cheng Guo Jian Huang Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study Breast Cancer Research Breast cancer Neoadjuvant chemotherapy Serum Metabolomics Acylcarnitine Essential amino acid |
| title | Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study |
| title_full | Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study |
| title_fullStr | Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study |
| title_full_unstemmed | Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study |
| title_short | Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study |
| title_sort | serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy a retrospective longitudinal study |
| topic | Breast cancer Neoadjuvant chemotherapy Serum Metabolomics Acylcarnitine Essential amino acid |
| url | https://doi.org/10.1186/s13058-024-01956-w |
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