O257: A Transcriptome Analysis of Primary Breast Cancer with Discordant Brain Metastasis Subtype

Abstract

Abstract Introduction Brain metastasis (BM) occurs in 15-30% of breast cancer (BC) cases. In the era of personalised medicine, knowledge of the BM subtype is of increasing importance. However, there is often discordance between breast primary (BP) subtype and its BM. Improvements in stereotactic radiosurgery and neuroradiology have greatly reduced the number patients undergoing surgical resection. Therefore, identifying BM subtype poses a therapeutic challenge. Methods This study included 116 patients with breast cancer brain metastasis on CTRIAL-IE 09/07. Clinical subtype was evaluated using immunohistochemistry (IHC) results for oestrogen receptor (ER), progesterone receptor (PR) and HER2. 63 BP RNA sequencing (RNA-Seq) samples were analysed to identify differentially expressed genes in ER positive (ER+) primaries that subsequently lost ER in BM vs. ER+ primaries that retained ER. Results 34 (29.3%) of BPs were ER+/HER2- vs. 19 (16.4%) brain metastases, 50 (43.1%) BPs were HER2+ vs. 60 (51.7%) metastases, 32 (27.6%) BPs were TNBC vs. 37 (31.9%) metastases. The most common receptor switches were loss of ER 20/62 (32.36%), loss of PR 17/30 (56.7%) and gain of HER2 11/65 (16.9%). RNA-Seq differential expression analysis of ER+ primary/ER- BM vs. ER+ primary/ER+ BM found ALB, CPA1, GOLGA8G were significantly underexpressed in patients that subsequently lost ER, conversely MUC2, AREG and HSPB1 were significantly overexpressed. Conclusion This study profiles receptor discordance between primary BC and its matched BM. Future studies of differentially expressed genes at a transcript level may predict BM subtype using primary RNA-Seq data and allow for a more tailored treatment approach.