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HER2 expression, copy number variation and survival outcomes in HER2-low non-metastatic breast cancer: an international multicentre cohort study and TCGA-METABRIC analysis
DC Field | Value | Language |
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dc.contributor.author | Tan, Ryan S. Y. C. | - |
dc.contributor.author | Ong, Whee S. | - |
dc.contributor.author | Lee, Kyung-Hun | - |
dc.contributor.author | Lim, Abner H. | - |
dc.contributor.author | Park, Seri | - |
dc.contributor.author | Park, Yeon H. | - |
dc.contributor.author | Lin, Ching-Hung | - |
dc.contributor.author | Lu, Yen-Shen | - |
dc.contributor.author | Ono, Makiko | - |
dc.contributor.author | Ueno, Takayuki | - |
dc.contributor.author | Naito, Yoichi | - |
dc.contributor.author | Onishi, Tatsuya | - |
dc.contributor.author | Lim, Geok-Hoon | - |
dc.contributor.author | Tan, Su-Ming | - |
dc.contributor.author | Lee, Han-Byoel | - |
dc.contributor.author | Ryu, Han S. | - |
dc.contributor.author | Han, Wonshik | - |
dc.contributor.author | Tan, Veronique K. M. | - |
dc.contributor.author | Wong, Fuh-Yong | - |
dc.contributor.author | Im, Seock-Ah | - |
dc.contributor.author | Tan, Puay H. | - |
dc.contributor.author | Chan, Jason Y. | - |
dc.contributor.author | Yap, Yoon-Sim | - |
dc.date.accessioned | 2022-03-21T04:10:50Z | - |
dc.date.available | 2022-03-21T04:10:50Z | - |
dc.date.issued | 2022-03-17 | - |
dc.identifier.citation | BMC Medicine. 2022 Mar 17;20(1):105 | - |
dc.identifier.uri | https://doi.org/10.1186/s12916-022-02284-6 | - |
dc.identifier.uri | https://hdl.handle.net/10371/177072 | - |
dc.description.abstract | Abstract
Background HER2-low breast cancer (BC) is currently an area of active interest. This study evaluated the impact of low expression of HER2 on survival outcomes in HER2-negative non-metastatic breast cancer (BC). Methods Patients with HER2-negative non-metastatic BC from 6 centres within the Asian Breast Cancer Cooperative Group (ABCCG) (n = 28,280) were analysed. HER2-low was defined as immunohistochemistry (IHC) 1+ or 2+ and in situ hybridization non-amplified (ISH−) and HER2-zero as IHC 0. Relapse-free survival (RFS) and overall survival (OS) by hormone receptor status and HER2 IHC 0, 1+ and 2+ ISH− status were the main outcomes. A combined TCGA-BRCA and METABRIC cohort (n = 1967) was also analysed to explore the association between HER2 expression, ERBB2 copy number variation (CNV) status and RFS. Results ABCCG cohort median follow-up was 6.6 years; there were 12,260 (43.4%) HER2-low BC and 16,020 (56.6%) HER2-zero BC. The outcomes were better in HER2-low BC than in HER2-zero BC (RFS: centre-adjusted hazard ratio (HR) 0.88, 95% CI 0.82–0.93, P < 0.001; OS: centre-adjusted HR 0.82, 95% CI 0.76–0.89, P < 0.001). On multivariable analysis, HER2-low status was prognostic (RFS: HR 0.90, 95% CI 0.85–0.96, P = 0.002; OS: HR 0.86, 95% CI 0.79–0.93, P < 0.001). These differences remained significant in hormone receptor-positive tumours and for OS in hormone receptor-negative tumours. Superior outcomes were observed for HER2 IHC1+ BC versus HER2-zero BC (RFS: HR 0.89, 95% CI 0.83–0.96, P = 0.001; OS: HR 0.85, 95% CI 0.78–0.93, P = 0.001). No significant differences were seen between HER2 IHC2+ ISH− and HER2-zero BCs. In the TCGA-BRCA and METABRIC cohorts, ERBB2 CNV status was an independent RFS prognostic factor (neutral versus non-neutral HR 0.71, 95% CI 0.59–0.86, P < 0.001); no differences in RFS by ERBB2 mRNA expression levels were found. Conclusions HER2-low BC had a superior prognosis compared to HER2-zero BC in the non-metastatic setting, though absolute differences were modest and driven by HER2 IHC 1+ BC. ERBB2 CNV merits further investigation in HER2-negative BC. | - |
dc.title | HER2 expression, copy number variation and survival outcomes in HER2-low non-metastatic breast cancer: an international multicentre cohort study and TCGA-METABRIC analysis | - |
dc.type | Journal Article | - |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s) | - |
dc.date.updated | 2022-03-20T04:16:09Z | - |
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