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Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases.

Publication ,  Journal Article
Sambade, MJ; Prince, G; Deal, AM; Trembath, D; McKee, M; Garrett, A; Keith, K; Ramirez, J; Midkiff, B; Blackwell, K; Sammons, S; Leone, JP ...
Published in: Breast Cancer Res Treat
July 2019

PURPOSE: Brain metastases (BM) are a complication of advanced breast cancer (BC). Histology of melanoma BM offers prognostic value; however, understanding the microenvironment of breast cancer brain metastases (BCBM) is less characterized. This study reports on four histological biomarkers, gliosis, immune infiltrate, hemorrhage, necrosis, and their prognostic significance in BCBM. METHODS: A biobank of 203 human tissues from patients who underwent craniotomy for BCBM was created across four academic institutions. Degree of gliosis, immune infiltrate, hemorrhage, and necrosis were identified and scored via representative H&E stain (0-3+). Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards regression evaluated prognostic value of the biomarkers in the context of standard clinical characteristics. RESULTS: BCBM subtype (available for n = 158) was 36% Her2+, 26% hormone receptor (HR)+/Her2- 38% HR-/Her2- (triple negative, TN). Gliosis was observed in 82% (116/141) of BCBM, with immune infiltrate 44% (90/201), hemorrhage 82% (166/141), and necrosis 87% (176/201). Necrosis was significantly higher in TNBC (p < 0.01). Presence of gliosis, immune infiltrate, and hemorrhage correlated with improved OS (p = 0.03, p = 0.03, p = 0.1), while necrosis correlated with inferior OS (p = 0.01). Improved OS was associated with gliosis in TN (p = 0.02), and immune infiltrate (p = 0.001) and hemorrhage (p = 0.07) in HER2+. In a multivariable model for OS, incorporating these biomarkers with traditional clinical variables improved the model fit (p < 0.001). CONCLUSION: Gliosis confers superior prognosis in TNBC BM; immune infiltrate and hemorrhage correlate with superior prognosis in HER2+ BCBM. Understanding the metastatic microenvironment of BCBM refines prognostic considerations and may unveil novel therapeutic strategies.

Duke Scholars

Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

July 2019

Volume

176

Issue

2

Start / End Page

321 / 328

Location

Netherlands

Related Subject Headings

  • Tumor Microenvironment
  • Triple Negative Breast Neoplasms
  • Survival Analysis
  • Prognosis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Humans
  • Female
  • Craniotomy
  • Brain Neoplasms
 

Citation

APA
Chicago
ICMJE
MLA
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Sambade, M. J., Prince, G., Deal, A. M., Trembath, D., McKee, M., Garrett, A., … Anders, C. (2019). Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases. Breast Cancer Res Treat, 176(2), 321–328. https://doi.org/10.1007/s10549-019-05211-1
Sambade, Maria J., Grace Prince, Allison M. Deal, Dimitri Trembath, Megan McKee, Amy Garrett, Kevin Keith, et al. “Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases.Breast Cancer Res Treat 176, no. 2 (July 2019): 321–28. https://doi.org/10.1007/s10549-019-05211-1.
Sambade MJ, Prince G, Deal AM, Trembath D, McKee M, Garrett A, et al. Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases. Breast Cancer Res Treat. 2019 Jul;176(2):321–8.
Sambade, Maria J., et al. “Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases.Breast Cancer Res Treat, vol. 176, no. 2, July 2019, pp. 321–28. Pubmed, doi:10.1007/s10549-019-05211-1.
Sambade MJ, Prince G, Deal AM, Trembath D, McKee M, Garrett A, Keith K, Ramirez J, Midkiff B, Blackwell K, Sammons S, Leone JP, Brufsky A, Morikawa A, Brogi E, Seidman A, Ewend M, Carey LA, Moschos SJ, Hamilton RL, Vincent B, Anders C. Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases. Breast Cancer Res Treat. 2019 Jul;176(2):321–328.
Journal cover image

Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

July 2019

Volume

176

Issue

2

Start / End Page

321 / 328

Location

Netherlands

Related Subject Headings

  • Tumor Microenvironment
  • Triple Negative Breast Neoplasms
  • Survival Analysis
  • Prognosis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Humans
  • Female
  • Craniotomy
  • Brain Neoplasms