Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-Analysis
An elevated serum HER2 extracellular domain is associated with poor prognosis in breast cancer, but the relationship between sHER2 and the efficacy of different modalities remains controversial. Herein, we aimed to evaluate the prognostic value of serum HER2 extracellular domain (sHER2 ECD) in breas...
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MDPI AG
2022-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/19/4551 |
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| author | Yun Wu Lixi Li Di Zhang Fei Ma |
| author_facet | Yun Wu Lixi Li Di Zhang Fei Ma |
| author_sort | Yun Wu |
| collection | DOAJ |
| description | An elevated serum HER2 extracellular domain is associated with poor prognosis in breast cancer, but the relationship between sHER2 and the efficacy of different modalities remains controversial. Herein, we aimed to evaluate the prognostic value of serum HER2 extracellular domain (sHER2 ECD) in breast cancer and to identify its correlation with the efficacy of different treatment regimens. A systematic search of the PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases was conducted to identify studies exploring the association between HER2 ECD level and clinical outcomes among patients with breast cancer. Using the random effects models, pooled hazard ratios (HRs), and odds ratios (ORs) with 95% confidence intervals (CI), were calculated for progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), and the objective response rate (ORR). Heterogeneity was further evaluated by subgroup and sensitivity analysis. Overall, 40 studies comprising 12,229 patients were included in this systematic review and meta-analysis. Elevated HER2 ECD levels were associated with worse PFS (HR 1.74, 95% CI 1.40–2.17; <i>p</i> < 0.001), and this effect was observed in patients treated with chemotherapy (HR 1.81, 95% CI 1.37–2.39; <i>p</i> < 0.001), endocrine therapy (HR 1.91, 95% CI 1.57–2.32; <i>p</i> < 0.001), and trastuzumab (HR 1.74, 95% CI 1.31–2.30; <i>p</i> < 0.001). However, this association was not present in patients treated with tyrosine kinase inhibitors (TKIs) (HR 1.44, 95% CI 0.85–2.43, <i>p</i> = 0.17). The HRs/ORs for an elevated HER2 ECD level for DFS, OS, and ORR were 2.73 (95% CI 2.17–3.42; <i>p</i> < 0.001), 2.13 (95% CI 1.77–2.57; <i>p</i> < 0.001), and 0.80 (95% CI 0.49–1.31; <i>p</i> = 0.381), respectively. An elevated sHER2 ECD was an unfavorable prognostic factor in breast cancer but did not affect the efficacy of tyrosine kinase inhibitors such as lapatinib. Detection of sHER2 ECD may be helpful for clinicians selecting the appropriate anti-HER2 therapy for patients with HER2-positive breast cancer. |
| first_indexed | 2024-03-09T21:59:21Z |
| format | Article |
| id | doaj.art-250ac7c2ae844e98a3f802eed8cf0cca |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:59:21Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-250ac7c2ae844e98a3f802eed8cf0cca2023-11-23T19:52:38ZengMDPI AGCancers2072-66942022-09-011419455110.3390/cancers14194551Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-AnalysisYun Wu0Lixi Li1Di Zhang2Fei Ma3Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, ChinaAn elevated serum HER2 extracellular domain is associated with poor prognosis in breast cancer, but the relationship between sHER2 and the efficacy of different modalities remains controversial. Herein, we aimed to evaluate the prognostic value of serum HER2 extracellular domain (sHER2 ECD) in breast cancer and to identify its correlation with the efficacy of different treatment regimens. A systematic search of the PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases was conducted to identify studies exploring the association between HER2 ECD level and clinical outcomes among patients with breast cancer. Using the random effects models, pooled hazard ratios (HRs), and odds ratios (ORs) with 95% confidence intervals (CI), were calculated for progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), and the objective response rate (ORR). Heterogeneity was further evaluated by subgroup and sensitivity analysis. Overall, 40 studies comprising 12,229 patients were included in this systematic review and meta-analysis. Elevated HER2 ECD levels were associated with worse PFS (HR 1.74, 95% CI 1.40–2.17; <i>p</i> < 0.001), and this effect was observed in patients treated with chemotherapy (HR 1.81, 95% CI 1.37–2.39; <i>p</i> < 0.001), endocrine therapy (HR 1.91, 95% CI 1.57–2.32; <i>p</i> < 0.001), and trastuzumab (HR 1.74, 95% CI 1.31–2.30; <i>p</i> < 0.001). However, this association was not present in patients treated with tyrosine kinase inhibitors (TKIs) (HR 1.44, 95% CI 0.85–2.43, <i>p</i> = 0.17). The HRs/ORs for an elevated HER2 ECD level for DFS, OS, and ORR were 2.73 (95% CI 2.17–3.42; <i>p</i> < 0.001), 2.13 (95% CI 1.77–2.57; <i>p</i> < 0.001), and 0.80 (95% CI 0.49–1.31; <i>p</i> = 0.381), respectively. An elevated sHER2 ECD was an unfavorable prognostic factor in breast cancer but did not affect the efficacy of tyrosine kinase inhibitors such as lapatinib. Detection of sHER2 ECD may be helpful for clinicians selecting the appropriate anti-HER2 therapy for patients with HER2-positive breast cancer.https://www.mdpi.com/2072-6694/14/19/4551breast cancerHER2 ECDprognosismeta-analysis |
| spellingShingle | Yun Wu Lixi Li Di Zhang Fei Ma Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-Analysis Cancers breast cancer HER2 ECD prognosis meta-analysis |
| title | Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-Analysis |
| title_full | Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-Analysis |
| title_fullStr | Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-Analysis |
| title_short | Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-Analysis |
| title_sort | prognostic value of the serum her2 extracellular domain level in breast cancer a systematic review and meta analysis |
| topic | breast cancer HER2 ECD prognosis meta-analysis |
| url | https://www.mdpi.com/2072-6694/14/19/4551 |
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