Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases


Huang, RSP ORCID: 0000-0001-8395-5168, Haberberger, J, McGregor, K, Mata, DA, Decker, B, Hiemenz, MC, Lechpammer, M, Danziger, N, Schiavone, K, Creeden, J et al (show 12 more authors) (2021) Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases Oncologist, 26 (10). pp. 835-844. ISSN 1083-7159, 1549-490X

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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.

Item Type: Article
Uncontrolled Keywords: Comprehensive genomic profiling, Biomarkers, Breast carcinoma, Brain metastases
Divisions: Faculty of Health & Life Sciences
Faculty of Health & Life Sciences > Clinical Directorate
Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 21 Jun 2021 08:06
Last Modified: 22 Jan 2026 12:48
DOI: 10.1002/onco.13855
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3126839
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