Abstract 225P
Background
Although hormone receptor (HR)-positive breast cancer generally shows a favorable prognosis for endocrine therapy, overcoming its resistance is a major challenge. MET alterations are frequently observed in various cancers and have been reported to play a role in chemotherapy resistance and poor prognosis. We investigated the prognostic values of MET-enriched CTCs, along with cfDNA-derived ESR1 and PIK3CA copy number and mutation status in HR+HER2- metastatic breast cancer (MBC) patients.
Methods
Patients with MBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated using the GenoCTC® and MET-enriched or EpCAM-enriched CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed by droplet digital PCR kits (Gencurix Inc., South Korea). cfDNA concentrations were calculated using ESR1 gene copy numbers from blood plasma.
Results
Sixty-three HR+/HER2- MBC patients were analyzed. Twenty-five (39.7%) patients had one or more MET-enriched or EpCAM-enriched CTCs detected from 4mL of blood each. Kaplan-Meier survival analysis showed MET-enriched CTCs, ESR1 mutations, and cfDNA concentrations were significantly associated with progression-free survival (PFS) (p=0.0026, 0.0064, and 0.011, respectively). However, EpCAM-enriched CTCs and PIK3CA mutations were not statistically significant with PFS (p=0.38 and 0.86, respectively). Multivariate analysis showed that both MET-enriched CTCs (HR=3.5, 95%CI=1.3-9.5, p=0.014) and cfDNA concentrations (HR=2.2, 95%CI=1.1-4.6, p=0.031) were independent predictors for PFS in HR+/HER2- MBC.
Conclusions
MET-enriched CTCs, and cfDNA concentrations calculated by ESR1 copy numbers are significant independent predictors of disease progression in HR+HER2- MBC. It was also demonstrated that MET enriched CTCs and cfDNA analysis could provide complementary information on disease progression, emphasizing the importance of the integrated liquid biopsy.
Clinical trial identification
The study protocol was approved by the institutional review board at SMC (IRB No. 2019-08-119).
Editorial acknowledgement
Legal entity responsible for the study
Samsung medical center.
Funding
Ministry of Health & Welfare, Ministry of Education, Republic of Korea.
Disclosure
N.Y. Kim: Financial Interests, Personal, Stocks/Shares, with stock option: ABION - Perpetual Pharmaceutical Pearl Provider. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Roche, Novartis, MSD, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Roche, Novartis, MSD; Financial Interests, Institutional, Other, Research Grant: AstraZeneca, Pfizer, Roche, MSD; Non-Financial Interests, Principal Investigator: AstraZeneca, Pfizer, Novartis, MSD, Lilly, Roche, Daiichi Sankyo. Y.K. Shin: Financial Interests, Personal, Stocks/Shares: ABION - Perpetual Pharmaceutical Pearl Provider; Non-Financial Interests, Personal, Invited Speaker: ABION - Perpetual Pharmaceutical Pearl Provider. All other authors have declared no conflicts of interest.