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Brain metastasis as the first and only metastatic relapse site portends worse survival in patients with advanced HER2 + breast cancer

  • Epidemiology
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Abstract

Purpose

Current systemic therapy guidelines for patients with HER2 + breast cancer brain metastases (BCBrM) diverge based on the status of extracranial disease (ECD). An in-depth understanding of the impact of ECD on outcomes in HER2 + BCBrM has never been performed. Our study explores the implications of ECD status on intracranial progression-free survival (iPFS) and overall survival (OS) after first incidence of HER2 + BCBrM and radiation.

Methods

A retrospective analysis was performed of 151 patients diagnosed with initial HER2 + BCBrM who received radiation therapy to the central nervous system (CNS) at Duke between 2008 and 2021. The primary endpoint was iPFS defined as the time from first CNS radiation treatment to intracranial progression or death. OS was defined as the time from first CNS radiation or first metastatic disease to death. Systemic staging scans within 30 days of initial BCBrM defined ECD status as progressive, stable/responding or none (isolated brain relapse).

Results

In this cohort, > 70% of patients had controlled ECD with either isolated brain relapse (27%) or stable/responding ECD (44%). OS from initial metastatic disease to death was markedly worse for patients with isolated intracranial relapse (median = 28.4 m) compared to those with progressive or stable/responding ECD (48.8 m and 71.5 m, respectively, p = 0.0028). OS from first CNS radiation to death was significantly worse for patients with progressive ECD (16.9 m) versus stable/responding (36.6 m) or isolated intracranial relapse (28.4 m, p = 0.007). iPFS did not differ statistically based on ECD status. Receipt of systemic therapy after first BCBrM significantly improved iPFS (HR 0.45, 95% CI: 0.25–0.81, p = 0.008) and OS (HR: 0.43 (95% CI: 0.23–0.81); p = 0.001).

Conclusion

OS in patients with HER2 + isolated BCBrM was inferior to those with concurrent progressive or stable/responding ECD. Studies investigating initiation of brain-penetrable HER2-targeted therapies earlier in the disease course of isolated HER2 + intracranial relapse patients are warranted.

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Data availability

The datasets generated and analyzed during the current study are not publicly available as they contain identifying information but available from the corresponding author on reasonable request.

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Funding

Funding for this project was provided to Laura Noteware by the Stead Scholarship Program of the Duke University Department of Medicine. Scott Floyd is supported by grants from the NIH (NIH 5R01-NS100866-05, NIH U01TR0033715-01, and NIH 5R38-CA245204-02) and the American Cancer Society (13394-RSG-19–030-01-DMC). Additional research funding from PUMA, Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G1-Therapeutics, ZION, Novartis, and Pfizer were provided to Carey Anders. Sarah Sammons receives institutional funding from Astra Zeneca, Abbvie, Bristol Myers Squibb, Eli Lilly, SEAGEN, and Sermonix. The authors declare that no additional funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Duke University School of Medicine, Durham, North Carolina, USA

    Laura Noteware

  2. Biostatistics Shared Resource, Duke Cancer Institute, Durham, North Carolina, USA

    Gloria Broadwater & James E. Herndon II

  3. Department of Medicine, University of California, San Francisco, California, USA

    Nicole Dalal

  4. Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA

    James E. Herndon II

  5. Duke Cancer Institute, Durham, North Carolina, USA

    Laura Alder, Scott Floyd, Amanda E. D. Van Swearingen, Carey K. Anders & Sarah Sammons

  6. Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA

    Scott Floyd & William Giles

  7. Duke Center for Brain and Spine Metastasis, Duke University Medical Center, 10 Bryan Searle Drive, Seeley G. Mudd Bldg., Room 449-A, Durham, North Carolina, USA

    Amanda E. D. Van Swearingen, Carey K. Anders & Sarah Sammons

Authors
  1. Laura Noteware
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  2. Gloria Broadwater
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  4. Laura Alder
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  6. Scott Floyd
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  9. Carey K. Anders
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  10. Sarah Sammons
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Corresponding author

Correspondence to Sarah Sammons.

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Conflict of interest

Carey Anders has been a compensated consultant for Genentech, Eisai, IPSEN, Seattle Genetics, Astra Zeneca, Novartis, Immunomedics, Elucida, and Athenex. Dr. Anders also receives royalties from UpToDate, Jones and Bartlett. Sarah Sammons is a compensated consultant at Foundation Medicine, Astra Zeneca, Daichii Sankyo, Eli Lilly, Pfizer, Sermonix, and Novartis. The additional authors have no relevant financial or non-financial interests to disclose.

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Noteware, L., Broadwater, G., Dalal, N. et al. Brain metastasis as the first and only metastatic relapse site portends worse survival in patients with advanced HER2 + breast cancer. Breast Cancer Res Treat 197, 425–434 (2023). https://doi.org/10.1007/s10549-022-06799-7

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  • DOI: https://doi.org/10.1007/s10549-022-06799-7

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