1. Serial Analysis of Circulating Tumor Cells in Metastatic Breast Cancer Receiving First-Line Chemotherapy
- Author
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Magbanua, Mark Jesus M, Hendrix, Laura H, Hyslop, Terry, Barry, William T, Winer, Eric P, Hudis, Clifford, Toppmeyer, Deborah, Carey, Lisa Anne, Partridge, Ann H, Pierga, Jean-Yves, Fehm, Tanja, Vidal-Martínez, José, Mavroudis, Dimitrios, Garcia-Saenz, Jose A, Stebbing, Justin, Gazzaniga, Paola, Manso, Luis, Zamarchi, Rita, Antelo, María Luisa, De Mattos-Arruda, Leticia, Generali, Daniele, Caldas, Carlos, Munzone, Elisabetta, Dirix, Luc, Delson, Amy L, Burstein, Harold J, Qadir, Misbah, Ma, Cynthia, Scott, Janet H, Bidard, François-Clément, Park, John W, and Rugo, Hope S
- Subjects
Cancer ,Prevention ,Breast Cancer ,Clinical Research ,Breast Neoplasms ,Female ,Humans ,Neoplastic Cells ,Circulating ,Prognosis ,Progression-Free Survival ,Proportional Hazards Models ,Reproducibility of Results ,Retrospective Studies ,Treatment Outcome ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundWe examined the prognostic significance of circulating tumor cell (CTC) dynamics during treatment in metastatic breast cancer (MBC) patients receiving first-line chemotherapy.MethodsSerial CTC data from 469 patients (2202 samples) were used to build a novel latent mixture model to identify groups with similar CTC trajectory (tCTC) patterns during the course of treatment. Cox regression was used to estimate hazard ratios for progression-free survival (PFS) and overall survival (OS) in groups based on baseline CTCs, combined CTC status at baseline to the end of cycle 1, and tCTC. Akaike information criterion was used to select the model that best predicted PFS and OS.ResultsLatent mixture modeling revealed 4 distinct tCTC patterns: undetectable CTCs (56.9% ), low (23.7%), intermediate (14.5%), or high (4.9%). Patients with low, intermediate, and high tCTC patterns had statistically significant inferior PFS and OS compared with those with undetectable CTCs (P < .001). Akaike Information Criterion indicated that the tCTC model best predicted PFS and OS compared with baseline CTCs and combined CTC status at baseline to the end of cycle 1 models. Validation studies in an independent cohort of 1856 MBC patients confirmed these findings. Further validation using only a single pretreatment CTC measurement confirmed prognostic performance of the tCTC model.ConclusionsWe identified 4 novel prognostic groups in MBC based on similarities in tCTC patterns during chemotherapy. Prognostic groups included patients with very poor outcome (intermediate + high CTCs, 19.4%) who could benefit from more effective treatment. Our novel prognostic classification approach may be used for fine-tuning of CTC-based risk stratification strategies to guide future prospective clinical trials in MBC.
- Published
- 2021