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Breast cancer subtype and intracranial recurrence patterns after brain-directed radiation for brain metastases

  • Daniel N. CagneyEmail author
  • Nayan Lamba
  • Sofia Montoya
  • Puyao Li
  • Luke Besse
  • Allison M. Martin
  • Rachel H. Brigell
  • Paul J. Catalano
  • Paul D. Brown
  • Jose P. Leone
  • Shyam K. Tanguturi
  • Daphne A. Haas-Kogan
  • Brian M. Alexander
  • Nancy U. Lin
  • Ayal A. Aizer
Clinical trial

Abstract

Purpose

Brain metastases from breast cancer are frequently managed with brain-directed radiation but the impact of subtype on intracranial recurrence patterns after radiation has not been well-described. We investigated intracranial recurrence patterns of brain metastases from breast cancer after brain-directed radiation to facilitate subtype-specific management paradigms.

Methods

We retrospectively analyzed 349 patients with newly diagnosed brain metastases from breast cancer treated with brain-directed radiation at Brigham and Women’s Hospital/Dana-Farber Cancer Institute between 2000 and 2015. Patients were stratified by subtype: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−), HER2+ positive (HER2+), or triple-negative breast cancer (TNBC). A per-metastasis assessment was conducted. Time-to-event analyses were conducted using multivariable Cox regression.

Results

Of the 349 patients, 116 had HR+/HER2− subtype, 164 had HER2+ subtype, and 69 harbored TNBC. Relative to HR+/HER2− subtype, local recurrence was greater in HER2+ metastases (HR 3.20, 95% CI 1.78–5.75, p < 0.001), while patients with TNBC demonstrated higher rates of new brain metastases after initial treatment (HR 3.16, 95% CI 1.99–5.02, p < 0.001) and shorter time to salvage whole brain radiation (WBRT) (HR 3.79, 95% CI 1.36–10.56, p = 0.01) and salvage stereotactic radiation (HR 1.86, 95% CI 1.11–3.10, p = 0.02).

Conclusions

We identified a strong association between breast cancer subtype and intracranial recurrence patterns after brain-directed radiation, particularly local progression for HER2+ and distant progression for TNBC patients. If validated, the poorer local control in HER2+ brain metastases may support evaluation of novel local therapy-based approaches, while the increased distant recurrence in TNBC suggests the need for improved systemic therapy and earlier utilization of WBRT.

Keywords

Breast cancer Brain metastases Recurrence Subtype HER2 Radiation 

Notes

Compliance with ethical standards

Conflict of interest

Daniel N. Cagney is a recipient of research support from NH Theraguix. Paul Brown reports personal fees from UpToDate (current) and personal fees as DSMB member Novella Clinical (2016) outside the submitted work. Dr. Leone reports that the institution (University of Iowa) received research funding from Merck. Dr. Leone reports funding from Kazia, Lilly, and Seattle Genetics. Daphne A. Haas-Kogan is advisory board member for Cellworks and reports clinical trial support from Novartis. Dr. Lin reports research grants from Pfizer, Genentech/Roche, Novartis, Seattle Genetics, and consulting fees from Pfizer, Genentech/Roche, Novartis, Seattle Genetics, Daichii, and Puma. Dr Alexander reports personal fees from Foundation Medicine, AbbVie, Schlesinger Associates, Bristol Myers Squibb, Precision Health Economics; grants from Puma, Celgene, Eli Lilly outside the submitted work. Dr. Aizer reports research funding from Varian Medical Systems and consulting fees from Novartis. The remaining authors declare no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10549_2019_5236_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Daniel N. Cagney
    • 1
    Email author
  • Nayan Lamba
    • 2
  • Sofia Montoya
    • 1
  • Puyao Li
    • 1
  • Luke Besse
    • 1
  • Allison M. Martin
    • 1
  • Rachel H. Brigell
    • 1
  • Paul J. Catalano
    • 3
    • 4
  • Paul D. Brown
    • 5
  • Jose P. Leone
    • 6
  • Shyam K. Tanguturi
    • 1
  • Daphne A. Haas-Kogan
    • 1
  • Brian M. Alexander
    • 1
  • Nancy U. Lin
    • 6
  • Ayal A. Aizer
    • 1
  1. 1.Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  2. 2.Harvard Medical SchoolBostonUSA
  3. 3.Department of BiostatisticsHarvard T.H. Chan School of Public HealthBostonUSA
  4. 4.Department of Biostatistics, and Computational BiologyDana-Farber Cancer InstituteBostonUSA
  5. 5.Department of Radiation OncologyMayo ClinicRochesterUSA
  6. 6.Department of Medical Oncology, Dana-Farber Cancer InstituteHarvard Medical SchoolBostonUSA

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