TY - JOUR
T1 - Evaluation of a Liquid Biopsy-Breast Cancer Methylation (LBx-BCM) Cartridge Assay for Predicting Early Disease Progression and Survival
T2 - TBCRC 005 Prospective Trial
AU - Visvanathan, Kala
AU - Cope, Leslie
AU - Fackler, Mary Jo
AU - Considine, Michael
AU - Sokoll, Lori
AU - Carey, Lisa A.
AU - Forero-Torres, Andres
AU - Ingle, James N.
AU - Lin, Nancy U.
AU - Nanda, Rita
AU - Storniolo, Anna Maria
AU - Tulac, Suzana
AU - Venkatesan, Neesha
AU - Wu, Natalie C.
AU - Marla, Sudhakar
AU - Campbell, Scott
AU - Bates, Michael
AU - Umbricht, Christopher B.
AU - Wolff, Antonio C.
AU - Sukumar, Saraswati
N1 - Publisher Copyright:
©2022 American Association for Cancer Research.
PY - 2023/2/16
Y1 - 2023/2/16
N2 - PURPOSE: We previously demonstrated that high levels of circulating methylated DNA are associated with subsequent disease progression in women with metastatic breast cancer (MBC). In this study, we evaluated the clinical utility of a novel liquid biopsy-breast cancer methylation (LBx-BCM) prototype assay using the GeneXpert cartridge system for early assessment of disease progression in MBC. EXPERIMENTAL DESIGN: The 9-marker LBx-BCM prototype assay was evaluated in TBCRC 005, a prospective biomarker study, using plasma collected at baseline, week 4, and week 8 from 144 patients with MBC. RESULTS: At week 4, patients with MBC with high cumulative methylation (CM) had a significantly shorter median PFS (2.88 months vs. 6.60 months, P = 0.001) and OS (14.52 months vs. 22.44 months, P = 0.005) compared with those with low CM. In a multivariable model, high versus low CM was also associated with shorter PFS (HR, 1.90; 95% CI, 1.20-3.01; P = 0.006). Change in CM from baseline to week 4 (OR, 4.60; 95% CI, 1.77-11.93; P = 0.002) and high levels of CM at week 4 (OR, 2.78; 95% CI, 1.29-5.99; P = 0.009) were associated with progressive disease at the time of first restaging. A robust risk model based on week 4 circulating CM levels was developed to predict disease progression as early as 3 months after initiating a new treatment. CONCLUSIONS: The automated LBx-BCM prototype assay is a promising clinical tool for detecting disease progression a month after initiating treatment in women with MBC undergoing routine care. The next step is to validate its clinical utility for specific treatments.
AB - PURPOSE: We previously demonstrated that high levels of circulating methylated DNA are associated with subsequent disease progression in women with metastatic breast cancer (MBC). In this study, we evaluated the clinical utility of a novel liquid biopsy-breast cancer methylation (LBx-BCM) prototype assay using the GeneXpert cartridge system for early assessment of disease progression in MBC. EXPERIMENTAL DESIGN: The 9-marker LBx-BCM prototype assay was evaluated in TBCRC 005, a prospective biomarker study, using plasma collected at baseline, week 4, and week 8 from 144 patients with MBC. RESULTS: At week 4, patients with MBC with high cumulative methylation (CM) had a significantly shorter median PFS (2.88 months vs. 6.60 months, P = 0.001) and OS (14.52 months vs. 22.44 months, P = 0.005) compared with those with low CM. In a multivariable model, high versus low CM was also associated with shorter PFS (HR, 1.90; 95% CI, 1.20-3.01; P = 0.006). Change in CM from baseline to week 4 (OR, 4.60; 95% CI, 1.77-11.93; P = 0.002) and high levels of CM at week 4 (OR, 2.78; 95% CI, 1.29-5.99; P = 0.009) were associated with progressive disease at the time of first restaging. A robust risk model based on week 4 circulating CM levels was developed to predict disease progression as early as 3 months after initiating a new treatment. CONCLUSIONS: The automated LBx-BCM prototype assay is a promising clinical tool for detecting disease progression a month after initiating treatment in women with MBC undergoing routine care. The next step is to validate its clinical utility for specific treatments.
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U2 - 10.1158/1078-0432.CCR-22-2128
DO - 10.1158/1078-0432.CCR-22-2128
M3 - Article
C2 - 36534524
AN - SCOPUS:85148250423
SN - 1078-0432
VL - 29
SP - 784
EP - 790
JO - Clinical cancer research : an official journal of the American Association for Cancer Research
JF - Clinical cancer research : an official journal of the American Association for Cancer Research
IS - 4
ER -