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Published on: May 17, 2019
Comprehensive genomic profiling to identify actionable alterations for breast cancer brain metastases in the Chinese
1Department 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.
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.
Insights
Genomic testing of breast cancer brain metastases (BCBM) reveals actionable targets in 94% of cases. Testing BCBM specimens is logical, as additional targets are found in about 31% of patients.
Area of Science:
- Oncology
- Genomics
- Translational Research
Background:
- Breast cancer brain metastasis (BCBM) presents a significant clinical challenge with poor prognosis.
- Identifying novel therapeutic targets for BCBM is crucial for improving patient outcomes.
Purpose of the Study:
- To identify potential actionable genomic targets in brain metastases (BMs) from breast cancer.
- To utilize the FoundationOne® CDx (F1CDx) assay for comprehensive genomic profiling of BCBM.
Main Methods:
- Analysis of formalin-fixed paraffin-embedded specimens from 49 BCBMs, 16 primary tumors (PTs), and 7 extracranial metastases (ECMs) using F1CDx.
- Assessment of tumor mutational burden (TMB) and tumor-infiltrated lymphocytes (TILs) in BCBM samples.
Main Results:
- Actionable genomic alterations (GAs) were identified in 94% of BCBM samples.
- TP53, PIK3CA, and ERBB2 were among the most frequently mutated genes and amplified regions, respectively.
- Approximately 31% of BCBMs harbored additional actionable GAs not present in matched primary tumors or extracranial metastases.
Conclusions:
- Tumor mutational burden (TMB) and tumor-infiltrated lymphocytes (TILs) were generally low in BCBM.
- Genomic testing of BCBM specimens is recommended to uncover additional actionable targets for personalized therapy.
- Consistent actionable GAs were observed between BCBMs and matched primary tumors/extracranial metastases, but unique alterations in BCBMs offer therapeutic opportunities.
