Longitudinal tumor fraction trajectories predict risk of progression in metastatic HR+ breast cancer patients undergoing CDK4/6 treatment

Autor: Nadia Dandachi, Florian Posch, Ricarda Graf, Christoph Suppan, Eva Valentina Klocker, Hannah Deborah Müller, Jörg Lindenmann, Angelika Terbuch, Ellen Heitzer, Marija Balic
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Molecular Oncology, Vol 15, Iss 9, Pp 2390-2400 (2021)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.12870
Popis: 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.
Databáze: Directory of Open Access Journals
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