Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases

Richard S.P. Huang, James Haberberger, Kimberly McGregor, Douglas A. Mata, Brennan Decker, Matthew C. Hiemenz, Mirna Lechpammer, Natalie Danziger, Kelsie Schiavone, James Creeden, Ryon P. Graf, Roy Strowd, Glenn J. Lesser, Evangelia D. Razis, Rupert Bartsch, Athina Giannoudis, Talvinder Bhogal, Nancy U. Lin, Lajos Pusztai, Jeffrey S. RossCarlo Palmieri, Shakti H. Ramkissoon

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Among patients with breast carcinoma who have metastatic disease, 15%–30% will eventually develop brain metastases. We examined the genomic landscape of a large cohort of patients with breast carcinoma brain metastases (BCBMs) and compared it with a cohort of patients with primary breast carcinomas (BCs). Material and Methods: We retrospectively analyzed 733 BCBMs tested with comprehensive genomic profiling (CGP) and compared them with 10,772 primary breast carcinomas (not-paired) specimens. For a subset of 16 triple-negative breast carcinoma (TNBC)–brain metastasis samples, programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) was performed concurrently. Results: A total of 733 consecutive BCBMs were analyzed. Compared with primary BCs, BCBMs were enriched for genomic alterations in TP53 (72.0%, 528/733), ERBB2 (25.6%, 188/733), RAD21 (14.1%, 103/733), NF1 (9.0%, 66/733), BRCA1 (7.8%, 57/733), and ESR1 (6.3%,46/733) (p <.05 for all comparisons). Immune checkpoint inhibitor biomarkers such as high tumor mutational burden (TMB-high; 16.2%, 119/733); high microsatellite instability (1.9%, 14/733); CD274 amplification (3.6%, 27/733); and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like mutational signature (5.9%, 43/733) were significantly higher in the BCBM cohort compared with the primary BC cohort (p <.05 for all comparisons). When using both CGP and PD-L1 IHC, 37.5% (6/16) of patients with TNBC brain metastasis were eligible for atezolizumab based on PD-L1 IHC, and 18.8% (3/16) were eligible for pembrolizumab based on TMB-high status. Conclusion: We found a high prevalence of clinically relevant genomic alterations in patients with BCBM, suggesting that tissue acquisition (surgery) and/or cerebrospinal fluid for CGP in addition to CGP of the primary tumor may be clinically warranted. Implications for Practice: This study found a high prevalence of clinically relevant genomic alterations in patients with breast carcinoma brain metastasis (BCBM), suggesting that tissue acquisition (surgery) and/or cerebrospinal fluid for comprehensive genomic profiling (CGP) in addition to CGP of the primary tumor may be clinically warranted. In addition, this study identified higher positive rates for FDA-approved immunotherapy biomarkers detected by CGP in patients with BCBM, opening a possibility of new on-label treatments. Last, this study noted limited correlation between tumor mutational burden and PD-L1 immunohistochemistry (IHC), which shows the importance of testing patients with triple-negative BCBM for immune checkpoint inhibitor eligibility with both PD-L1 IHC and CGP.

Original languageEnglish (US)
Pages (from-to)835-844
Number of pages10
JournalOncologist
Volume26
Issue number10
DOIs
StatePublished - Oct 2021
Externally publishedYes

Keywords

  • Biomarkers
  • Brain metastases
  • Breast carcinoma
  • Comprehensive genomic profiling

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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