Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial

Breast Cancer Research

Chiara Biagioni¹  Matteo Benelli¹  Dario Romagnoli¹  Alessandro M. Minisini²  Giuseppe Curigliano³  Valerio Conti⁴  Stefano Gabellini⁵  Erica Moretti⁵  Emanuela Risi⁵  Laura Biganzoli⁵  Silvia Cappadona⁵  Angelo Di Leo⁵  Amelia McCartney⁶  Martina Bonechi⁷  Francesca De Luca⁷  Francesca Galardi⁷  Ilenia Migliaccio⁷  Cristina Guarducci⁸  Luca Malorni⁹ 

[1] Bioinformatics Unit, Hospital of Prato, Prato, Italy;Department of Oncology, Azienda Sanitaria Universitaria del Friuli Centrale, Udine, Italy;Division of Early Drug Development, Istituto Europeo di Oncologia, IRCCS, Milan, Italy;Department of Haematology and Haemato-Oncology, University of Milan, Milan, Italy;Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Children’s Hospital A. Meyer-University of Florence, Florence, Italy;“Sandro Pitigliani” Medical Oncology Department, Hospital of Prato, Prato, Italy;“Sandro Pitigliani” Medical Oncology Department, Hospital of Prato, Prato, Italy;School of Clinical Sciences, Monash University, Melbourne, Australia;“Sandro Pitigliani” Translational Research Unit, Hospital of Prato, Prato, Italy;“Sandro Pitigliani” Translational Research Unit, Hospital of Prato, Prato, Italy;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA;“Sandro Pitigliani” Translational Research Unit, Hospital of Prato, Prato, Italy;“Sandro Pitigliani” Medical Oncology Department, Hospital of Prato, Prato, Italy;

关键词: Liquid biopsy;    CTCs;    Luminal breast cancer;    Metastatic;    Palbociclib;    CDK4/6 inhibitor;    ddPCR;    Biomarker;   

DOI  :  10.1186/s13058-021-01415-w

来源: Springer

【 摘 要 】

BackgroundCirculating tumor cells (CTCs) are prognostic in patients with advanced breast cancer (ABC). However, no data exist about their use in patients treated with palbociclib. We analyzed the prognostic role of CTC counts in patients enrolled in the cTREnd study, a pre-planned translational sub-study of TREnd (NCT02549430), that randomized patients with ABC to palbociclib alone or palbociclib plus the endocrine therapy received in the prior line of treatment. Moreover, we evaluated RB1 gene expression on CTCs and explored its prognostic role within the cTREnd subpopulation.MethodsForty-six patients with ER-positive, HER2-negative ABC were analyzed. Blood samples were collected before starting palbociclib treatment (timepoint T0), after the first cycle of treatment (timepoint T1), and at disease progression (timepoint T2). CTCs were isolated and counted by CellSearch® System using the CellSearch™Epithelial Cell kit. Progression-free survival (PFS), clinical benefit (CB) during study treatment, and time to treatment failure (TTF) after study treatment were correlated with CTC counts. Samples with ≥ 5 CTCs were sorted by DEPArray system® (DA). RB1 and GAPDH gene expression levels were measured by ddPCR.ResultsAll 46 patients were suitable for CTCs analysis. CTC count at T0 did not show significant prognostic value in terms of PFS and CB. Patients with at least one detectable CTC at T1 (n = 26) had a worse PFS than those with 0 CTCs (n = 16) (p = 0.02). At T1, patients with an increase of at least three CTCs showed reduced PFS compared to those with no increase (mPFS = 3 versus 9 months, (p = 0.004). Finally, patients with ≥ 5 CTCs at T2 (n = 6/23) who received chemotherapy as post-study treatment had a shorter TTF (p = 0.02). Gene expression data for RB1 were obtained from 19 patients. CTCs showed heterogeneous RB1 expression. Patients with detectable expression of RB1 at any timepoint showed better, but not statistically significant, outcomes than those with undetectable levels.ConclusionsCTC count seems to be a promising modality in monitoring palbociclib response. Moreover, CTC count at the time of progression could predict clinical outcome post-palbociclib. RB1 expression analysis on CTCs is feasible and may provide additional prognostic information. Results should be interpreted with caution given the small studied sample size.

【 授权许可】

CC BY