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

Breast Cancer Res Treat. 2019 Jul;176(1):171-179. doi: 10.1007/s10549-019-05236-6. Epub 2019 Apr 13.


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: Brain metastases; Breast cancer; HER2; Radiation; Recurrence; Subtype.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor
  • Biopsy
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / secondary*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / pathology*
  • Cause of Death
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Treatment Outcome


  • Biomarkers, Tumor