Comprehensive genomic profiling to identify actionable alterations for breast cancer brain metastases in the Chinese population

Q Lu; N Wang; K Jiang; H Zhou; P Zhang; J Zhang; S Wang; P Sun; F Xu

doi:10.1016/j.esmoop.2024.102389

Comprehensive genomic profiling to identify actionable alterations for breast cancer brain metastases in the Chinese population

ESMO Open. 2024 Mar;9(3):102389. doi: 10.1016/j.esmoop.2024.102389. Epub 2024 Mar 8.

Authors

Q Lu¹, N Wang², K Jiang², H Zhou², P Zhang², J Zhang², S Wang², P Sun³, F Xu⁴

Affiliations

¹ Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
² Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
³ Department of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China. Electronic address: sunpeng1@sysucc.org.cn.
⁴ Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China. Electronic address: xufei@sysucc.org.cn.

Abstract

Background: Breast cancer brain metastasis (BCBM) is a crucial issue in the treatment of breast cancer and is associated with poor prognosis. Therefore, novel therapeutic targets are urgently needed in clinical practice. In this study, we aimed to identify potential actionable targets in brain metastases (BMs) utilising the FoundationOne® CDx (F1CDx).

Patients and methods: Formalin-fixed paraffin-embedded archived specimens including 16 primary breast tumours (PTs), 49 BCBMs and 7 extracranial metastases (ECMs) from 54 patients who underwent surgery for BCBM were tested using F1CDx. Tumour-infiltrated lymphocytes (TILs) of BMs were also tested using haematoxylin-eosin staining.

Results: The median tumour mutational burden (TMB) and TILs in BMs were 5.0 (range 0-29) mut/Mb and 1.0% (range 0%-5.0%), respectively. High TMB (≥10 mut/Mb) was detected in four cases (8%). Genomic alterations (GAs) were detected in all samples. The top-ranked somatic mutations in BMs were TP53 (82%), PIK3CA (35%), MLL2 (22%), BRCA2 (14%) and ATM (14%) and the most prevalent copy number alterations were ERBB2 (64%), RAD21 (36%), CCND1 (32%), FGF19 (30%) and FGF3 (30%). The most prevalent GAs were relatively consistent between paired PTs and BMs. Actionable GAs were detected in 94% of all BMs. Consistent rate in actionable GAs was 38% (6/16) between paired PTs/ECMs and BMs. Compared to matched PTs/ECMs, additional actionable GAs (BRAF, FGFR1, PTEN, KIT and CCND1) were discovered in 31% (5/16) of the BMs.

Conclusions: TMB and TILs were relatively low in BCBMs. Comparable consistency in actionable GAs was identified between BCBMs and matched PTs/ECMs. It was, therefore, logical to carry out genomic testing for BCBMs to identify potential new therapeutic targets when BCBM specimens were available, as ∼31% of samples carried additional actionable GAs.

Keywords: actionable genomic alterations; breast cancer brain metastasis; genomic profiling; tumour mutational burden; tumour-infiltrating lymphocytes.

MeSH terms

Biomarkers, Tumor / genetics
Brain Neoplasms* / genetics
Brain Neoplasms* / secondary
Breast Neoplasms* / genetics
Breast Neoplasms* / pathology
China / epidemiology
Female
Gene Expression Profiling
Genomics
Humans
Mutation

Substances

Biomarkers, Tumor