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Impact of HER2-low status for patients with early-stage breast cancer and non-pCR after neoadjuvant chemotherapy: a National Cancer Database Analysis

  • Epidemiology
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Abstract

Purpose

To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting.

Methods

We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan–Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses.

Results

For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72–0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85–0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79–0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86–0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77–0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83–0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61–1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85–1.45), p = 0.44].

Conclusion

In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.

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Data availability

The data that support the findings of this study are available from the National Cancer Database, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with the permission of NCDB.

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Acknowledgements

The National Cancer Database (NCDB) is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC's NCDB and the hospitals participating in the CoC’s NCDB are the source of the de-identified data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.

The authors thank Ms. Li Kong, President of Academy of Clinical Research and Study, for coordinating this research work and communication.

Funding

This work was not funded.

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Authors and Affiliations

  1. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, 27710, USA

    Huiyue Li, Samantha M. Thomas, Yuanyuan Guo & Sheng Luo

  2. Duke Cancer Institute, Duke University, Durham, NC, 27710, USA

    Jennifer K. Plichta, Samantha M. Thomas & Qingyi Wei

  3. Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, 27710, USA

    Jennifer K. Plichta & Qingyi Wei

  4. Department of Surgery, Duke University School of Medicine, Durham, NC, 27710, USA

    Jennifer K. Plichta

  5. Merck & Co., Inc., Rahway, NJ, USA

    Kan Li

  6. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Yizi Jin & Jian Zhang

  7. Department of Phase I Clinical Trial Center, Fudan University Shanghai Cancer Center, No. 270, Dong’an Road, Shanghai, 200032, China

    Yizi Jin & Jian Zhang

  8. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Fei Ma

  9. Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Li Tang

  10. Department of Medicine, Duke University School of Medicine, Durham, NC, USA

    Qingyi Wei

  11. Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA

    You-Wen He

  12. Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Qichen Chen

  13. Department of Pathology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

    Yueping Liu

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  1. Huiyue Li
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Contributions

Conception and design: Huiyue Li, Qichen Chen, Jennifer K. Plichta, Sheng Luo, Jian Zhang. Material preparation, data collection and analysis: Huiyue Li, Sheng Luo, Samantha M. Thomas, Jennifer K. Plichta. The first draft of the manuscript was written by Huiyue Li and Yizi Jin, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jian Zhang or Sheng Luo.

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Competing interests

The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. The authors have no relevant financial or non-financial interests to disclose. Dr. J. Plichta was the recipient of research funding by the Color Foundation (PI: Plichta). She serves on the National Comprehensive Cancer Network (NCCN) Breast Cancer Screening Committee. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official view of the NIH and other organizations.

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The present study was granted Duke University Institutional Review Board exemption and waiver of informed consent due to the use of de-identified patient data.

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Li, H., Plichta, J.K., Li, K. et al. Impact of HER2-low status for patients with early-stage breast cancer and non-pCR after neoadjuvant chemotherapy: a National Cancer Database Analysis. Breast Cancer Res Treat 204, 89–105 (2024). https://doi.org/10.1007/s10549-023-07171-z

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