Analysis of clinical features, genomic landscapes and survival outcomes in HER2-low breast cancer
Abstract Background Novel human epidermal growth factor receptor 2 (HER2)-directed antibody–drug conjugates prompt the identification of the HER2-low subtype. However, the biological significance of HER2-low expression in breast cancer is unclear. Methods Clinical and genomic data of 579 metastatic...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-06-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04076-9 |
| _version_ | 1827933226040033280 |
|---|---|
| author | Juan Jin Bin Li Jianing Cao Ting Li Jian Zhang Jun Cao Mingchuan Zhao Leiping Wang Biyun Wang Zhonghua Tao Xichun Hu |
| author_facet | Juan Jin Bin Li Jianing Cao Ting Li Jian Zhang Jun Cao Mingchuan Zhao Leiping Wang Biyun Wang Zhonghua Tao Xichun Hu |
| author_sort | Juan Jin |
| collection | DOAJ |
| description | Abstract Background Novel human epidermal growth factor receptor 2 (HER2)-directed antibody–drug conjugates prompt the identification of the HER2-low subtype. However, the biological significance of HER2-low expression in breast cancer is unclear. Methods Clinical and genomic data of 579 metastatic breast cancer patients were reviewed from our next-generation sequencing (NGS) database and genomic analysis of early breast cancer patients from TCGA was also analyzed. Findings First, the clinicopathological characteristics of HER2-low patients were profoundly influenced by HR status and no difference of prognosis was observed between HER2-low and HER2-zero patients when paired by HR status, but notably HER2-low patients showed similar metastatic patterns to HER2-positive patients in the HR-positive (HR+ ) subgroup, with more brain and initial lung metastases and more cases of de novo stage IV breast cancer than HER2-zero patients. Second, among patients with primary HER2-low or HER2-zero tumors, the discordance of HER2 status between primary and metastatic tumors was significant, with 48.4% of patients with HER2-zero primary tumors exhibiting HER2-low phenotype in metastatic tumors in the HR+ subgroup. Third, within HR+ and HR-negative subtypes, HER2-low and HER2-zero tumors showed no substantial differences in mutation alterations and copy number variations. Forth, germline BRCA2 mutations were observed only in HER2-low patients in our NGS database, especially in HR+ HER2-low tumors. Finally, three molecular subtypes based on genomic alterations in HER2-low breast cancer were identified, which provided novel insights into heterogeneity in HER2-low breast cancer. Conclusions After correcting for HR expression, only marginal differences in clinical and molecular phenotypes were determined between HER2-low and HER2-zero breast cancer. Therefore, HER2-low breast cancer is insufficient to be defined as a distinct molecular entity, but rather a heterogenous disease. |
| first_indexed | 2024-03-13T07:21:47Z |
| format | Article |
| id | doaj.art-feeb8b6d8ae14d6982b8b819747c5496 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-13T07:21:47Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-feeb8b6d8ae14d6982b8b819747c54962023-06-04T11:37:18ZengBMCJournal of Translational Medicine1479-58762023-06-0121111610.1186/s12967-023-04076-9Analysis of clinical features, genomic landscapes and survival outcomes in HER2-low breast cancerJuan Jin0Bin Li1Jianing Cao2Ting Li3Jian Zhang4Jun Cao5Mingchuan Zhao6Leiping Wang7Biyun Wang8Zhonghua Tao9Xichun Hu10Department of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer CenterAbstract Background Novel human epidermal growth factor receptor 2 (HER2)-directed antibody–drug conjugates prompt the identification of the HER2-low subtype. However, the biological significance of HER2-low expression in breast cancer is unclear. Methods Clinical and genomic data of 579 metastatic breast cancer patients were reviewed from our next-generation sequencing (NGS) database and genomic analysis of early breast cancer patients from TCGA was also analyzed. Findings First, the clinicopathological characteristics of HER2-low patients were profoundly influenced by HR status and no difference of prognosis was observed between HER2-low and HER2-zero patients when paired by HR status, but notably HER2-low patients showed similar metastatic patterns to HER2-positive patients in the HR-positive (HR+ ) subgroup, with more brain and initial lung metastases and more cases of de novo stage IV breast cancer than HER2-zero patients. Second, among patients with primary HER2-low or HER2-zero tumors, the discordance of HER2 status between primary and metastatic tumors was significant, with 48.4% of patients with HER2-zero primary tumors exhibiting HER2-low phenotype in metastatic tumors in the HR+ subgroup. Third, within HR+ and HR-negative subtypes, HER2-low and HER2-zero tumors showed no substantial differences in mutation alterations and copy number variations. Forth, germline BRCA2 mutations were observed only in HER2-low patients in our NGS database, especially in HR+ HER2-low tumors. Finally, three molecular subtypes based on genomic alterations in HER2-low breast cancer were identified, which provided novel insights into heterogeneity in HER2-low breast cancer. Conclusions After correcting for HR expression, only marginal differences in clinical and molecular phenotypes were determined between HER2-low and HER2-zero breast cancer. Therefore, HER2-low breast cancer is insufficient to be defined as a distinct molecular entity, but rather a heterogenous disease.https://doi.org/10.1186/s12967-023-04076-9HER2-low breast cancerAntibody–drug conjugatesHER2 expressionHER2 dynamicsMetastatic breast cancerHeterogeneity |
| spellingShingle | Juan Jin Bin Li Jianing Cao Ting Li Jian Zhang Jun Cao Mingchuan Zhao Leiping Wang Biyun Wang Zhonghua Tao Xichun Hu Analysis of clinical features, genomic landscapes and survival outcomes in HER2-low breast cancer Journal of Translational Medicine HER2-low breast cancer Antibody–drug conjugates HER2 expression HER2 dynamics Metastatic breast cancer Heterogeneity |
| title | Analysis of clinical features, genomic landscapes and survival outcomes in HER2-low breast cancer |
| title_full | Analysis of clinical features, genomic landscapes and survival outcomes in HER2-low breast cancer |
| title_fullStr | Analysis of clinical features, genomic landscapes and survival outcomes in HER2-low breast cancer |
| title_full_unstemmed | Analysis of clinical features, genomic landscapes and survival outcomes in HER2-low breast cancer |
| title_short | Analysis of clinical features, genomic landscapes and survival outcomes in HER2-low breast cancer |
| title_sort | analysis of clinical features genomic landscapes and survival outcomes in her2 low breast cancer |
| topic | HER2-low breast cancer Antibody–drug conjugates HER2 expression HER2 dynamics Metastatic breast cancer Heterogeneity |
| url | https://doi.org/10.1186/s12967-023-04076-9 |
| work_keys_str_mv | AT juanjin analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer AT binli analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer AT jianingcao analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer AT tingli analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer AT jianzhang analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer AT juncao analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer AT mingchuanzhao analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer AT leipingwang analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer AT biyunwang analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer AT zhonghuatao analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer AT xichunhu analysisofclinicalfeaturesgenomiclandscapesandsurvivaloutcomesinher2lowbreastcancer |