Real-world data analysis of next generation sequencing and protein expression in metastatic breast cancer patients.

Abstract

e13005 Background: Next generation sequencing (NGS) together with protein expression analysis is back bone of molecularly targeted therapy in precision medicine. The present study shows the retrospective analysis of our experience with NGS using a panel of 324 genes in combination with protein expression in patients with metastatic breast cancer (mBC) over the last 18 months. The primary objective of this study was to analyze the prevalence of individual genetic alterations combined with protein expression to define potential targets for an individualized therapy. Methods: We analyzed 41 patients with advanced BC using solid tumor genomic profiling test. The test was used to detect clinically relevant genomic alterations (point mutations, indels, rearrangements, CNAs, tumor mutation burden (TMB) and microsatellite instability (MSI)) and to support the selection of appropriate targeted therapy. The protein expression (hormon receptors, ERBB2 and PDL1) of tumors was analyzed by immunohistochemistry (IHC). Results: The most common BC subtypes were HR+/ERBB2- (n = 20), followed by triple-negative (n = 15), and HER2+ BC (n = 9). 41 different genetic alterations were reported. Most patients had more than one genetic alteration (n = 27), as determined by NGS. The most common alterations were PIK3CA (n = 14), out of which 11 (78%) were hormone-receptor positive/ERBB2 negative. Conclusions: The NGS of mBC supports the decision for the most promising treatment option in 58,5% of our patients with a Tier I evidence. For an appropriate treatment decision it is necessary to evaluate gene alterations und protein expression of metastases in account. For an appropriate interpretation of rare gene alterations in mBC basket trials on basis of real world data are necessary. We founded the OnkoVision alliance to bring MTB into clinically routine and to identify appropriate patients for basket trials.