3870 - A retrospective gene expression analysis of surgically-removed Breast Cancer Brain Metastasis (BCBM)

Background

The incidence of BCBM is increasing as a result of both improved diagnostic techniques and longer survival due to better treatment approaches. However, it is still a challenging situation occasioned by the poor responses to different standard therapies, representing an unmet medical need. Determining the molecular profile may be clinically relevant in order to improve the outcome of our patients (pts).

Methods

This is an observational retrospective study including BC-pts who had undergone surgery of BCBM in Hospital Clinic (Barcelona, Spain) between January 2000 and December 2017. RNA was isolated from FFPE tumor tissue and the expression of 55 BC-related genes was assessed on the nCounter. Median progression free survival (mPFS) and overall survival (mOS) were calculated using the Kaplan-Meier method. The association of the expression of each gene with mPFS was evaluated using univariate Cox-models. The same gene expression assay was tested BCBM-paired primary tumor samples.

Results

20 pts with resected BMBC were included. Median age at diagnosis of BCBM was 57.8years (y). mOS from diagnosis of BCBM was 20.22 months (range, 0.67-64.50months). The intrinsic subtype distribution was 45% Basal-like, 20% HER2-enriched (HER2-E), 10% Luminal A, 20% Luminal B and 5% Normal-like. High expression of ESR1and PGR (determined as above the median) and low expression of MKI67were related with better mOS (p = 0.008, p = 0.038 and p = 0.0165). 9 matched-paired samples of primary BC and BCBM were analyzed and 4 (44.4%) PAM50 discordances (2 Luminal B shifted to Luminal A, 1 Normal-like to Basal-like and 1 HER2-E to Luminal B) were observed. Finally, down-regulation of CD8Aand PDL1expression between primary and BCBM (p = 0.0234 and p = 0.0367, respectively) was observed.

Conclusions

Non-luminal intrinsic subtypes are more prevalent in resected BCBM, and gene expression might predict OS. Our data suggest that BCBM can elude the immune surveillance through downregulation of immune genes leading to an immunosuppressed environment. Our analysis shows the value of analyzing gene expression both by cancer subtype and metastatic origin, but further characterization is needed.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain.

Funding

Fundación Científica Asociación Española Contra el Cáncer (PRÁCTICAS AECC CURSO ACADÉMICO 2018 to M.M-L).

Disclosure

M. Vidal: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: Novartis. M. Muñoz: Travel / Accommodation / Expenses: Roche. A. Prat: Advisory / Consultancy: Nanostring Tech. All other authors have declared no conflicts of interest.