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Relationship between HER2-low status and efficacy of CDK4/6 inhibitors in advanced breast cancer: a real-world study

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International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Aims and objectives

Human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) is a new entity considered a biologically distinct subtype from HER2-zero BC. However, the importance of HER2 low expression on the activity of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) remains unclear.

Methods/materials

We conducted a single-center retrospective study including hormone receptor-positive (HR +) /HER2- metastatic BC (mBC) patients treated with CDK4/6i plus endocrine treatment (ET) as first-line therapy. Clinical outcomes were analyzed according to HER2 expression.

Results

258 women were analyzed with a median follow-up of 25.4 months; 39.9% had HER2 low, and 60.1% had HER2 zero BC. Median progression-free survival (mPFS) in the HER2-low group was 27.6 months compared with 44.3 months in the HER2-zero group (p = 0.341). In patients receiving ribociclib, the mPFS in the HER2-low group was 24.2 months compared with 53.1 months in the HER2-zero group (multivariate-adjusted HR: 1.981, 95 Cl 1.094–3.586; p = 0.024). The survival probabilities at 24, 36 and 48 months for the HER2 low and HER2 zero groups were 82%, 69%, 69% and 83%, 75% and 69%, respectively (p = 0.336). Objective response rate (p = 0.179) and disease control rate (p = 0.338) did not significantly differ between HER-2-low and HER-2-zero groups.

Conclusions

The mPFS in the Her2-zero group was almost twice that of the Her2-low group, but the difference was not statistically significant. mPFS was significantly longer in the HER2-zero group compared to the HER2-low group in patients receiving ribociclib. More prospective studies are needed to understand the actual consequences of this biomarker.

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Data availability

Data supporting the findings of this study are available from the corresponding author upon request.

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Authors and Affiliations

  1. Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey

    T. Önder, Ö. Ateş, İ. Öner & C. Karaçin

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  1. T. Önder
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  2. Ö. Ateş
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  3. İ. Öner
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  4. C. Karaçin
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Contributions

All authors contributed to the article and approved the submitted version. T.Ö, C.K and Ö.A designed the research, analyzed the data and drafted the paper. T.Ö, C.K, Ö.A, and İ.Ö were mainly responsible for data collection and analysis. T.Ö and C.K were primarily responsible for statistical analysis.

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Correspondence to T. Önder.

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The authors declare that they have no competing interests.

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The studies involving human participants were reviewed and approved by The ethics committee of Health Sciences University, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital. According to national legislation and institutional standards, participation in this study did not require written informed consent.

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Önder, T., Ateş, Ö., Öner, İ. et al. Relationship between HER2-low status and efficacy of CDK4/6 inhibitors in advanced breast cancer: a real-world study. Int J Clin Oncol (2024). https://doi.org/10.1007/s10147-024-02528-w

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