ESMO Congress 2023 | OncologyPRO

Abstract 488P

Background

Breast cancer brain metastasis (BCBM) is an significant issue in the treatment of breast cancer and always leads to poor prognosis. Novel therapeutic targets are needed in clinical practice. In this study, we aimed to identify potential actionable targets in brain metastases utilizing the FoundationOne® CDx (F1CDx).

Methods

Formalin-fixed paraffin-embedded (FFPE) specimens including 17 primary tumors, 49 BCBMs and 7 extra-cranial metastases from 54 patients who underwent surgery for BCBM were tested by F1CDx. Tumor infiltrated lymphocytes (TILs) of BCBM were also tested by hematoxylin-eosin staining.

Results

The median tumor mutation burden (TMB) and TILs were 5.0 (range: 0- 29) Muts/Mb and 1.0 (range: 0- 5) respectively in BCBMs. High TMB (>10 Muts/MB) were detected in 3 BCBMs. Genomic alterations(GAs) were detected in all samples. The top-ranked mutated genes in BCBMs were TP53(81.6%), PIK3CA(34.7%), MLL2(22.4%), BRCA2(14.3%) and ATM(14.3%); and the most prevalent copy number alterations (CNAs) were ERBB2(57.1%), CDK12(36.7%), CCND1(28.6%),FGF19 (26.5%), and MYC (22.4%). ATM mutation was detected in 7 BCBMs while none in primary tumors, although without statistically significant difference. The most prevalent GAs were relatively consistent between paired primary and BCBMs. Actionable GAs were detected in 93.9% of all BCBMs and consistent rate were 54.5% (6/11) between paired primary and BCBMs. Compared to matched primary tumors, reduced actionable GAs were found in 4 BCBMs and additional actionable GAs were discovered in only one BCBM.

Conclusions

TMB and TILs was relatively low in BCBMs. Comparable consistency of actionable GAs was identified between primary and BCBMs. It was reasonable to treat BCBM according to genomic profiling of primary tumors if BCBM specimens were unavailable since possibility to find additional therapeutic targets was relatively low.