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Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China

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Abstract

Background

The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status.

Objective

To investigate the prognostic impact of HER2-low in different HR subgroups.

Patients and Methods

We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 (n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals—36 months, 60 months, and 120 months.

Results

HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS (p = 0.046) and DFS (p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS (p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models.

Conclusions

HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients’ HR status.

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Author notes

  1. Qichen Dai, Kexin Feng, Gang Liu, Xiang Wang, Lin Feng, Yipeng Wang have contributed equally to this work.

Authors and Affiliations

  1. Department of Breast Surgery, National Cancer Center|National Clinical Research Center for Cancer|Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Qichen Dai, Kexin Feng, Gang Liu, Han Cheng, Xiangyu Tong, Xiang Wang & Yipeng Wang

  2. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center| National Clinical Research Center for Cancer| Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Lin Feng

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Correspondence to Xiang Wang, Lin Feng or Yipeng Wang.

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Funding

This work was funded by the CAMS Innovation Fund for Medical Sciences (CIFMS, ID Number: 2021-I2M-1-014) and the Beijing Hope Run Special Fund of Cancer Foundation of China (ID Number: LC2022A02).

Competing Interests

Qichen Dai, Kexin Feng, Gang Liu, Han Cheng, Xiangyu Tong, Xiang Wang, Lin Feng, and Yipeng Wang declare they have no conflicts of interest that might be relevant to the contents of this manuscript.

Ethics Approval & Consent to Participate

This study was constructed as a retrospective design, obtaining data from previous medical records. Our study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline and obtained a waiver of informed consent due to the retrospective design. This study was approved by the National GCP Center for Anticancer Drugs, The Independent Ethics Committee (Approval Number: 23/350-4092).

Consent for Publication

Not applicable.

Availability of Data and Material

The datasets generated during and/or analyzed during the current study are not publicly available due to the confidentiality regulations concerning patient personal information by our institutional ethics committee but are available in an anonymized form from the corresponding author on reasonable request.

Code Availability

Not applicable.

Author’s Contributions

XW, LF and YW contributed to the conception, supervision, and funding of the study. QD, KF and GL carried out the data retrieval, collection, and analyses. QD wrote the original draft. HC and XT were responsible for the critical revision of the manuscript or important intellectual content. GL managed the resources and interpretation. All authors read and approved the final manuscript.

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Dai, Q., Feng, K., Liu, G. et al. Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China. Targ Oncol 19, 81–93 (2024). https://doi.org/10.1007/s11523-023-01030-z

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