Abstract P4-01-13: CTC enumeration and characterization has predictive and prognostic implications in patients with metastatic breast cancer treated with exemestane plus the mTOR inhibitor everolimus

Autor: Stella Apostolaki, Christos Nikolaou, Maria Spiliotaki, Sofia Agelaki, Vassilis Georgoulias, Dimitris Mavroudis, Eleni Politaki, Maria Papadaki
Rok vydání: 2015
Předmět:
Zdroj: Cancer Research. 75:P4-01
ISSN: 1538-7445
0008-5472
Popis: Background: The utility of CTC enumeration in predicting patient (pt) outcome has been demonstrated in metastatic breast cancer (MBC) treated with chemotherapy or endocrine therapy. In this study we evaluated the clinical impact of CTC assessment in terms of both enumeration and characterization in breast cancer pts treated with exemestane plus everolimus. Patients and methods: Thirty-nine pts with hormone receptor (HR)-positive, HER2-negative MBC, received exemestane plus everolimus. CTC enumeration in peripheral blood (7.5 ml) was performed before treatment (n=39), post cycles 1 (n=39) and 3 (n=29), on disease re-evaluation and on relapse, whichever occurred first, using the CellSearch System. CTC characteristics were determined at the same time points by immunofluorescence (IF) analysis of PBMC cytospins (106 cells), triple stained with pancytokeratin (CK) antibody along with Ki67 and M30 as proliferation and apoptosis markers, respectively, using the Ariol System. Patients were assessed by CT scans and bone scan, every 3 months or as clinically indicated. Results: At the cut-off of ≥ 1 CTC, 25 of 39 (64%) pts had detectable CTCs at baseline, 12 (31%) of 39 post-1st and 10 (34.5%) of 29 post-3rd cycle. Ten (25.6%) pts remained CTC(+) and 12 (30.8%) CTC(-) both at baseline and post-1st cycle; 15 (38.5%) CTC(+) pts turned to CTC(-) and 2 (5%) CTC(-) turned to (+). CTC positivity after the first cycle was associated with shorter median progression-free survival (PFS) compared to CTC(-) status (3.9 vs 8 mo, p=0.031). Shorter PFS was also recorded for pts that remained CTC(+) at both time points compared to all other (p=0.02). At the cut-offs of ≥ 2 and ≥ 5 CTCs, 16 (41%) and 9 (23%) pts were CTC(+) at baseline, respectively; post-1st cycle, 7 (18%) and 4 (10%) pts were CTC(+) (at ≥ 2 and ≥ 5 CTCs, respectively). Post-3rd cycle the positivity rate was 17% for both cut-offs and these pts had significantly shorter PFS compared to CTC(-) pts (3.7 vs 8.7 months, p=0.048). Efficacy assessment revealed partial response in 3 (7.7%) pts, stable disease in 27 (69.23%) and progressive disease (PD) in 8 (20.5%); 1 pt was non-evaluable for response. Among pts determined CTC(+) post-1st cycle (cut-off ≥ 2 CTCs), 57% progressed compared to 13% of CTC(-) pts (p=0.02). In addition, at the post-3rd cycle evaluation, pts with PD had significantly higher CTC counts compared to non-progressors (mean ± SEM; 10 ± 5.78/pt vs 1.62±0.83/pt, p=0.027). By the use of IF 43%, 44% and 40% of CTC(+) pts had proliferative [Ki67(+)/M30(-)] CTCs at baseline, post -1st and -3rd cycles, respectively (cut-off ≥ 1 CTC); 67%, 50% and 50% of those pts, respectively, experienced PD. Apoptotic [Ki67(-)/M30(+)] CTCs were detected in 14%, 22% and 60% of CTC(+) pts at baseline, post -1st and -3rd cycles, respectively; none of the pts with apoptotic CTCs experienced PD. Conclusions: CTC enumeration and characterization in terms of proliferation and apoptosis during the course of treatment has significant predictive and prognostic implications in patients with MBC receiving the combination of exemestane plus everolimus. Citation Format: Sofia Agelaki, Dimitris Mavroudis, Maria Spiliotaki, Eleni Politaki, Maria A Papadaki, Stella Apostolaki, Christos Nikolaou, Vassilis Georgoulias. CTC enumeration and characterization has predictive and prognostic implications in patients with metastatic breast cancer treated with exemestane plus the mTOR inhibitor everolimus [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-13.
Databáze: OpenAIRE
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