Serial analysis of ESR1 and PIK3CA mutations in cell-free DNA from metastatic breast cancer during 1st line endocrine therapy.

• DOI: 10.1200/jco.2024.42.16_suppl.e13060
• Publication Date: 2024-06-04T17:49:58Z
• Authors: Soo Yeon Baek; Meehyang Hong; Seungah Lee; Seulgi Joo; JungPil Jang; Chinkoo Jung; Sae Byul Lee; Tae-Kyung Yoo; Il Yong Chung; Hee Jeong Kim; Beom Seok Ko; Jong Won Lee; Byung Ho Son; Hyehyun Jeong; Jae Ho Jeong; Jin-Hee Ahn; Kyung Hae Jung; Sung-Bae Kim; Hee Jin Lee; Jisun KIM
• Keywords: Cell-free fetal DNA; Fulvestrant

e13060 Background: Activating mutations ofESR1 and PIK3CA genes are known mechanisms of endocrine resistance. Recent analysis supported benefit early intervention at presence ESR1 mutation in blood (bESR1) before clinical progression. We aimed to investigate detected cell-free DNA (cfDNA) from patients with hormone receptor-positive, HER2-negative metastatic breast cancer (MBC) its impact on progression-free survival (PFS). Methods: Thirty undergoing 1 st line therapy (ETx) were identified a prospective cohort. Seven hotspot the ligand binding domain tested cfDNA droplet digital polymerase chain reaction (ddPCR) assay (Genopeaks Co., Ltd). Eleven using amplicon-targeted sequencing method Ltd) both tumor cfDNA. PFS analyses performed Kaplan-Meier methods compared log-rank test. Results: examined serial samples 26 collected every 3-6 months. found 61.5% (16/26) any timepoint during 1st therapy, D538G being most common followed by Y537C 68.8% (11/16) polyclonal. Among 50.0% (8/16) bESR1 positive progression, 4 had progression while diagnosed concurrently, suggesting necessity closer intervals analyses. While did not affect overall, 18.8% within 6 months after ETx, displayed worse outcome (median 5 vs 52 months). Also, clearance subsequent (81.3%, 13/16) shown have better 41 14 8 mutation. Median between negative was 9 69.5% (16/23) diagnosis distant metastasis, among them 53.3% (8/15) co-occurrence mutations. primary tissue disease-free nor PFS, metastasis significantly (p = 0.041). Conclusions: Substantial number MBC plasma. Though it small-sized accurately assess statistical significance, we observed 1) detection (<6 months) 2) sustained palliative ETx. Patients without shorter than bESR1. prognostic supporting combined targeted therapy.