Abstract P5-01-21: PIK3CA and ESR1 mutations detected in circulating tumor DNA (ctDNA) are predictive factors for late-line hormone-based therapies in ER+/HER2- metastatic breast cancer (MBC)

Background: With more hormonal therapies (HT) based treatment (tx) available, predictive markers that could lead to a selection of the optimal tx is necessary. The predictive role of ctDNA mutations in ER+/HER2- MBC after prior HT is less well characterized in Asian patients (pts). Methods: ER+/HER2- MBC pts starting HT based salvage tx after refractory to at least one-line of HT were eligible. ctDNA was extracted from pre- and post-tx plasma and prepared for next-generation sequencing (NGS) analysis. The targeted NGS mutations included regions of ESR1 ligand-binding domain, PIK3CA mutation hotspots, and TP53 mutation hotspots. 96% of the samples were sequenced at an average depths >10000x using the Ion Torrent platform. Progression-free survival (PFS) was defined from the start of the salvage tx to the date of progression. Results: From 2015/08 to 2019/04, a total of 129 and 70 pts treated with HT based tx had pre- and post-tx ctDNA tested, respectively. The median age is 60 (32-92). 14%, 7%, 55%, and 19% of pts received HT only, HT + CDK4/6 inhibitor, HT + everolimus, and HT + metronomic chemotherapy, respectively. With mutation ctDNA > 0.5% as a threshold for positive calling, 79 (61.2%), 33 (25.6%), and 23 (17.8%) pts have at least one ESR1, PIK3CA, and TP53 mutation, respectively and 48 (37.3%) pts have >1 ESR1 mutation genotypes. When compared to other clinical trial data, Asian ER+ MBC pts had significantly higher ESR1 mutation rate as compared to the Western population (p Conclusion: PIK3CA and ESR1 Y537S and E380Q mutations detected by ctDNA had predictive impact for late-line HT based tx but PIK3CA mutation is a better predictor marker than ESR1 mutation in pts treated with HT + everolimus. Citation Format: Tom Wei-Wu Chen, Ming-Shen Dai, Dwang-Ying Chang, Ching-Hung Lin, I-Chun Chen, Ming-Yang Wang, Ling-Yi Huang, An Hsu, De-Wei Zhuo, Kien Thiam Tan, Yen-Jung Lu, Shu-Han Chang, Ann-Lii Cheng, Yen-Shen Lu. PIK3CA and ESR1 mutations detected in circulating tumor DNA (ctDNA) are predictive factors for late-line hormone-based therapies in ER+/HER2- metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-21.