Journal Article

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

Malorni, Luca, Minisini, Alessandro M., Cappadona, Silvia, Galardi, Francesca, Curigliano, Giuseppe, Risi, Emanuela, Romagnoli, Dario, Benelli, Matteo, Bonechi, Martina, McCartney, Amelia, Conti, Valerio, De Luca, Francesca, Biagioni, Chiara, Biganzoli, Laura, Di Leo, Angelo, Gabellini, Stefano, Guarducci, Cristina, Moretti, Erica, Migliaccio, Ilenia

2021

Overview

Background Circulating 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. Methods Forty-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. Results All 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. Conclusions CTC 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Biomarkers / Biomarkers, Tumor - blood / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Cancer / Cancer Research / Cancer therapies / CDK4/6 inhibitor / Cell Count / Cell survival / Chemotherapy / CTCs / Disease Progression / Drug therapy / Endocrine therapy / Epithelial cells / ErbB-2 protein / Female / Gene expression / Genes / Glyceraldehyde-3-phosphate dehydrogenase / Humans / Liquid biopsy / Luminal breast cancer / Medical prognosis / Metastasis / Metastatic / Neoplastic Cells, Circulating - drug effects / Neoplastic Cells, Circulating - metabolism / Neoplastic Cells, Circulating - pathology / Oncology / Oncology, Experimental / Palbociclib / Patients / Piperazines - therapeutic use / Progression-Free Survival / Protein Kinase Inhibitors - therapeutic use / Pyridines - therapeutic use / Receptor, ErbB-2 - deficiency / Receptors, Estrogen - metabolism / Receptors, Progesterone - metabolism / Research Article / Retinoblastoma Binding Proteins - metabolism / Retinoblastoma protein / Silicon / Statistical analysis / Surgical Oncology / Translation / Treatment Outcome / Tumor cells / Ubiquitin-Protein Ligases - metabolism