Breast cancer subtype and stage are prognostic of time from breast cancer diagnosis to brain metastasis development

Anurag Saraf, Christopher S. Grubb, Mark E. Hwang, Cheng Hung Tai, Cheng Chia Wu, Ashish Jani, Matthew E. Lapa, Jacquelyn I.S. Andrews, Sierra Vanderkelen, Steven R. Isaacson, Adam M. Sonabend, Sameer A. Sheth, Guy M. McKhann, Michael B. Sisti, Jeffrey N. Bruce, Simon K. Cheng, Eileen P. Connolly, Tony J.C. Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Breast cancer brain metastasis (BCBM) is associated with high morbidity and mortality. Patients with breast cancer risk factors associated with rapid development of BCBM could potentially benefit from early brain metastasis screening. We retrospectively reviewed all BCBM patients treated with brain radiotherapy at our institution from 1997 to 2015. Interval time to BCBM was defined as date of pathologic breast cancer diagnosis to date of radiographic evidence of brain metastasis. Patients were stratified by breast cancer molecular subtype and stage at diagnosis. Kaplan Meier analysis was conducted on time to development of BCBM. Breast cancer risk factors were correlated with time to BCBM on Cox proportion hazard analysis. The study cohort comprised 121 BCBM patients, with median interval time to BCBM of 46 months. Times to BCBM for Her2+/2HR+, Her2+, Her2−/HR+, and triple-negative (TNBC) subtypes were 70, 44, 42, and 28 months respectively (p = 0.002). Time to BCBM for stages I, II, III, and IV were 70, 54, 29, and 24 months, respectively (p = 0.000). BCBM patients were further stratified by both molecular subtype (TNBC vs. non-TNBC) and stage (I, II vs. III, IV). Median times to BCBM for non-TNBC/stage I–II, TNBC/stage I–II, non-TNBC stage III–IV, and TNBC/stage III–IV were 68, 47, 29, and 6 months respectively (p = 0.000). Subtype and stage were associated with shorter time to BCBM on multivariate analysis. Subtype and initial stage are independently correlated with decreased time to development of BCBM. Patients with advanced high stage and triple negative breast cancer develop brain metastases significantly earlier.

Original languageEnglish (US)
Pages (from-to)453-463
Number of pages11
JournalJournal of Neuro-Oncology
Issue number2
StatePublished - Sep 1 2017


  • Breast cancer
  • Risk factors
  • Time to brain metastasis
  • Triple negative

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research


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