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The emerging predictive and prognostic role of HER2 in HER2-negative early breast cancer: a retrospective study

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Abstract

Purpose

Many patients with early breast cancer (eBC) undergoing neoadjuvant chemotherapy do not achieve pathological complete response (pCR), which is a prognostic factor. We examined the role of HER2-low expression in predicting pCR and prognosis in HER2-negative eBC.

Methods

We evaluated patients with stage I-III HER2-negative BC, treated between 2013 and 2023 at The Royal Marsden NHS Foundation Trust, London. Tumors were classified based on estrogen receptor (ER) status and into HER2-low and HER2-zero subgroups. We analyzed pCR rates, relapse-free survival (RFS) and overall survival (OS).

Results

754 patients were included in the analysis. pCR rate was 8.9% in the ER+ /HER2-low, 16.5% in the ER+ /HER2-zero, 38.9% in the ER- ER-/HER2-low and 35.9% in the ER-/HER2-zero eBC (p < 0.001). Multivariable analysis showed a significantly lower pCR rate in HER2-low compared to HER2-zero BC in the ER+ subgroup. At a median follow-up of 63.8 months (59.9–67.4), we observed longer OS in HER2-low compared to HER2-zero patients in the overall and in the ER+ population. There was no predictive or prognostic impact of HER2-low status in the ER- population.

Conclusion

This study supports the interpretation of HER2 status as a possible prognostic and predictive biomarker for HER2-negative eBC, especially among patients with ER+ disease.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

The authors received no specific funding for this work.

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Author notes

  1. Alistair Ring and Nicolò Matteo Luca Battisti have contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine and Surgery, Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy

    Matilde Corianò, Chiara Tommasi, Benedetta Pellegrino & Antonino Musolino

  2. Breast Unit – Department of Medicine, The Royal Marsden NHS Foundation Trust, London, UK

    Matilde Corianò, Anh Thi Lan Dinh, Jazmine Needham, Hala Aziz, Nalinie Joharatnam-Hogan, Niamh Cunningham, Jasmin Waterhouse, Mingze Sun, Fiona Turkes, Sophie McGrath, Alicia Okines, Marina Parton, Nicholas Turner, Stephen Johnston, Alistair Ring & Nicolò Matteo Luca Battisti

  3. Vietnam National Cancer Hospital, Hanoi, Vietnam

    Anh Thi Lan Dinh

  4. University College London Medical School, London, UK

    Mingze Sun

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  1. Matilde Corianò
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Contributions

The study was designed and conceived by MC, AM, AR and NMLB. MC, ATLD, JN, HA, NJH, NC, JW, MS and FT contributed to data collection. The analysis was conducted by MC, and the results interpreted by MC, AM, AR, NMLB, SM, AO, MP, NT, SJ, BP and CT. The manuscript was first drafted by MC. MC, AM, AR and NMLB made substantial contributions to revising the successive drafts and all the authors approved the final version of the manuscript.

Corresponding author

Correspondence to Nicolò Matteo Luca Battisti.

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Corianò, M., Tommasi, C., Dinh, A.T.L. et al. The emerging predictive and prognostic role of HER2 in HER2-negative early breast cancer: a retrospective study. Breast Cancer Res Treat (2024). https://doi.org/10.1007/s10549-024-07336-4

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