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Effect of HER2-low expression on neoadjuvant efficacy in operable breast cancer

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Abstract

Objective

To investigate the effects of HER2-low expression (HER2-low) and HER2-zero expression (HER2-0) on the pathological complete response (pCR) rate and survival of patients following neoadjuvant chemotherapy.

Methods

Eighty-six patients were followed up. Patients were divided into HER2-0 (immunohistochemistry (IHC) score of 0 (IHC0)) and HER2-low (IHC1+ or IHC2+/in situ hybridization non-amplified (ISH-)) groups according to the IHC detection of puncture tissues. After neoadjuvant chemotherapy, the clinical characteristics, pCR rate and DFS were compared between the two groups.

Results

There were 24 (27.9%) cases with HER2-0 and 62 (72.1%) cases with HER2-low. Hormone receptor-positive (HR+) patients accounted for 77.4% of the HER2-low group, which was higher than 70.8% in the HER2-0 group, and there was no significant difference between the two groups (p = 0.524). There were statistical differences in the pT and pN stages between HER2-low and HER2-0 subgroups in the triple-negative breast cancer (TNBC) group after neoadjuvant chemotherapy. The HER2-low subgroup had an earlier T stage (p = 0.009), and the ratio of N0 to N1 in the HER2-low and HER2-0 subgroups was 92.9% and 71.4%, respectively (p = 0.037). The Ki-67 index and median PR value were significantly lower in the HER2-low group after neoadjuvant chemotherapy (p = 0.002, p = 0.018). The HER2 IHC score was altered in the HER2-low group, and the HER-2 (2+) score changed significantly (p = 0.002). Seventy-eight patients with complete immunohistochemical data were analyzed. The discordance rate of the IHC score of HER2 after neoadjuvant chemotherapy was 38.5%, and eight patients with HER2-low showed HER2-0 status, with a discordance rate of 10.3%. After neoadjuvant chemotherapy, The pCR rate was significantly lower in the HER2-low group compared with that in the HER2-0 group (4.8% vs. 8.3%; p = 0.914), but the recurrence and metastasis rates were lower in the HER2-low group (9.7% vs. 20.8%; p = 0.165). There were no differences in DFS between the two groups at 6, 12, 24, and 36 months (p = 0.076; p = 0.518; p = 0.245; p = 0.406). The subgroup analysis demonstrated no significant difference in DFS between HER2-low and HER2-0 subgroups in the HR + and TNBC groups (p = 0.141, p = 0.637).

Conclusion

This retrospective study indicates that HER2-low has no significant effect on neoadjuvant efficacy in operable breast cancer. There were no statistical differences in clinical characteristics, pCR rate, and DFS between the HER2-low and the HER2-0 groups. There was no evidence that a HER2-low status constitutes a unique biological subtype, suggesting that more clinical data might be needed to verify these observations.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

The authors would like to express their gratitude to EditSprings (https://www.editsprings.cn) for the expert linguistic services provided.

Funding

Beijing Xisike Clinical Oncology Research Foundation.

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Authors and Affiliations

  1. Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China

    Xiaoli Yi, Meili Ma, Dongshuai Huang & Yan Zhang

  2. The Affiliated Hospital of Qingdao University, Qingdao, China

    Shasha Hu

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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection and analysis were performed by XY, YZ, SH, MM and DH. The first draft of the manuscript was written by XY and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yan Zhang.

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital) (2023− 004).

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The study was done after agreement from the local ethics committee and written informed consent was obtained from all participants and/or their guardians.

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Yi, X., Hu, S., Ma, M. et al. Effect of HER2-low expression on neoadjuvant efficacy in operable breast cancer. Clin Transl Oncol 26, 880–890 (2024). https://doi.org/10.1007/s12094-023-03318-y

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