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Dandachi, N; Posch, F; Graf, R; Suppan, C; Klocker, EV; Müller, HD; Lindenmann, J; Terbuch, A; Heitzer, E; Balic, M.
Longitudinal tumor fraction trajectories predict risk of progression in metastatic HR+ breast cancer patients undergoing CDK4/6 treatment.
Mol Oncol. 2021; 15(9):2390-2400 Doi: 10.1002/1878-0261.12870 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Dandachi Nadia
Co-Autor*innen der Med Uni Graz
Balic Marija
Graf Ricarda
Heitzer Ellen
Klocker Eva Valentina
Lindenmann Jörg
Müller Hannah Deborah
Posch Florian
Suppan Christoph
Terbuch Angelika

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Despite improved clinical outcomes, intrinsic or acquired resistance to CDK4/6 inhibitor treatment has limited the success of this treatment in HR+ HER2- metastatic breast cancer patients. Biomarkers are urgently needed, and longitudinal biomarker measurements may harbor more dynamic predictive and prognostic information compared to single time point measurements. The aim of this study was to explore the longitudinal evolution of circulating tumor fractions within cell-free DNA assessed by an untargeted sequencing approach during CDK4/6 therapy and to quantify the potential association between longitudinal z-score measurements and clinical outcome by using joint models. Forty-nine HR+ HER2- metastatic breast cancer patients were enrolled, and z-score levels were measured at baseline and during 132 follow-up visits (median number of measurements per patient = 3, 25th -75th percentile: 3-5, range: 1-8). We observed higher baseline z-score levels (estimated difference 0.57, 95% CI: 0.147-0.983, P-value = 0.008) and a constant increase of z-score levels over follow-up time (overall P-value for difference in log z-score over time = 0.024) in patients who developed progressive disease. Importantly, the joint model revealed that elevated z-score trajectories were significantly associated with higher progression risk (HR of log z-score at any time of follow-up = 3.3, 95% CI, 1.44-7.55, P = 0.005). In contrast, single z-score measurement at CDK4/6 inhibitor treatment start did not predict risk of progression. In this prospective study, we demonstrate proof-of-concept that longitudinal z-score trajectories rather than single time point measurements may harbor important dynamic information on the development of disease progression in HR+ HER2- breast cancer patients undergoing CDK4/6 inhibitor treatment.

Find related publications in this database (Keywords)
6 therapy
circulating tumor DNA
joint model
longitudinal biomarker analysis
metastatic breast cancer
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