Maria Spiliotaki1, Galatea Kallergi2, Christos Nikolaou1, Nikolaos Xenidis3,4, Eleni Politaki1, Stella Apostolaki1, Nefeli Georgoulia3, Filippos Koinis1,3,5, Nikolaos Tsoukalas3,6, Dora Hatzidaki1,3, Athanasios Kotsakis1,3,5, Vassilis Georgoulias7,8. 1. Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Crete, Greece. 2. Department of Biochemistry, University of Crete Medical School, Heraklion, Crete, Greece. 3. Hellenic Oncology Research Group (HORG), 55 Lombardou str, 11474, Athens, Greece. 4. Department of Medical Oncology, Medical School, Democritus University of Thrace, Xanthi, Greece. 5. Department of Medical Oncology, Faculty of Medicine, School of Health Sciences, University Hospital of Larissa & Laboratory of Oncology, University of Thessaly Mezourlo, Larissa, Thessaly, Greece. 6. Medical Oncology Unit, NIMITS Hospital, Athens, Greece. 7. Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Crete, Greece. georgoul@uoc.gr. 8. Hellenic Oncology Research Group (HORG), 55 Lombardou str, 11474, Athens, Greece. georgoul@uoc.gr.
Abstract
PURPOSE: Detection of CTCs represents a poor prognostic factor in patients with early and metastatic breast cancer (mBC) and treatment with everolimus-exemestane (E/E) is an established effective treatment in hormone receptor-positive/HER2-negative mBC patients. The effect of E/E on CTCs in mBC patients was prospectively investigated. METHODS: CTCs from 50 pre-treated patients with mBC receiving E/E were analyzed using the CellSearch (CS) platform and triple immunofluorescence (IF) staining for cytokeratin, M30 and Ki67 expression to assess their proliferative and apoptotic status. RESULTS: CTCs (by CS) were detected in 64% of patients before treatment and E/E administration resulted in their decreased prevalence [(n = 18; 36%, p = 0.004) and (n = 7; 19.4%, p = 0.019) post-1st and post-3rd treatment cycle, respectively] whereas it was significantly increased at disease progression (PD: 61%) compared to post-1st and post-3rd cycle (p = 0.049 and p = 0.021, respectively). Ki67-positive CTCs were detected in 60%, 60%, 17% and 50% of patients before treatment, post-1st, post-3rd cycle and at PD, respectively, while the opposite was observed for M30-positive CTCs (0% at baseline, 10% after the 1st cycle, 50% after the 3rd cycle and 0% at PD). The detection of even ≥ 1 CTC/5 ml after one cycle was associated with decreased PFS (3.3 vs 9.0 months, p = 0.025) whereas the detection of even ≥ 2 CTCs at PD was associated with decreased OS (32.4 vs 19.5 months; p = 0.009). CONCLUSIONS: The combination of E/E resulted in early elimination of proliferating CTCs in mBC patients and this effect was associated with a favorable clinical outcome.
PURPOSE: Detection of CTCs represents a poor prognostic factor in patients with early and metastatic breast cancer (mBC) and treatment with everolimus-exemestane (E/E) is an established effective treatment in hormone receptor-positive/HER2-negative mBC patients. The effect of E/E on CTCs in mBC patients was prospectively investigated. METHODS: CTCs from 50 pre-treated patients with mBC receiving E/E were analyzed using the CellSearch (CS) platform and triple immunofluorescence (IF) staining for cytokeratin, M30 and Ki67 expression to assess their proliferative and apoptotic status. RESULTS: CTCs (by CS) were detected in 64% of patients before treatment and E/E administration resulted in their decreased prevalence [(n = 18; 36%, p = 0.004) and (n = 7; 19.4%, p = 0.019) post-1st and post-3rd treatment cycle, respectively] whereas it was significantly increased at disease progression (PD: 61%) compared to post-1st and post-3rd cycle (p = 0.049 and p = 0.021, respectively). Ki67-positive CTCs were detected in 60%, 60%, 17% and 50% of patients before treatment, post-1st, post-3rd cycle and at PD, respectively, while the opposite was observed for M30-positive CTCs (0% at baseline, 10% after the 1st cycle, 50% after the 3rd cycle and 0% at PD). The detection of even ≥ 1 CTC/5 ml after one cycle was associated with decreased PFS (3.3 vs 9.0 months, p = 0.025) whereas the detection of even ≥ 2 CTCs at PD was associated with decreased OS (32.4 vs 19.5 months; p = 0.009). CONCLUSIONS: The combination of E/E resulted in early elimination of proliferating CTCs in mBC patients and this effect was associated with a favorable clinical outcome.
Entities:
Keywords:
Breast cancer; CTCs; Everolimus; Exemestane; mTOR inhibitor
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