Prognostic Value of Fas/Fas Ligand Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Patients with Metastatic Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Cell Lines
2.3. PBMC and CTC Enrichment
2.4. Immunofluorescence (IF)
2.5. Assessment of Fas/FasL Expression on CTCs and PBMCs
2.6. Statistical Analysis
3. Results
3.1. Patient and Disease Characteristics
3.2. CTC Detection and Characterization According to Fas/FasL Expression
3.3. Evaluation of Fas/FasL Expression on PBMCs and Correlation with CTC Phenotype
3.4. Correlation of CTC and PBMC Parameters with Patient and Disease Characteristics
3.5. Correlation of CTC and PBMC Parameters with Survival Measures
3.5.1. CTC Detection and Phenotype
3.5.2. PBMC Phenotype
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Metastatic BC Patients (n = 98) | n (%) |
---|---|
Age, years; median (range) | 59 (29–84) |
Menopausal status | |
Pre-menopausal | 27 (27.6) |
Post-menopausal | 69 (70.4) |
Unknown | 2 (2) |
Histology | |
Ductal | 81 (82.7) |
Lobular | 9 (9.2) |
Mixed | 5 (5.1) |
Unknown | 3 (3.1) |
Stage at diagnosis | |
I–III | 70 (71.4) |
IV | 28 (28.6) |
Subtype | |
ER+ and/or PR+/HER2- | 63 (64.3) |
HER2+ | 23 (23.5) |
Triple negative | 12 (12.2) |
Metastases type | |
Visceral only | 27 (27.6) |
Non-visceral only | 29 (29.6) |
Both | 39 (39.8) |
Unknown | 3 (3.1) |
Disease sites | |
1–2 | 62 (63.3) |
>2 | 33 (33.7) |
Unknown | 3 (3.1) |
Prior adjuvant treatment | |
Chemotherapy | 49 (50) |
Hormone therapy | 16 (16.3) |
No | 30 (30.6) |
Unknown | 3 (3.1) |
First-line treatment | |
Chemotherapy | 86 (87.8) |
Hormone therapy | 12 (12.2) |
Response to treatment at first evaluation | |
Partial response (PR) | 38 (38.8) |
Stable disease (SD) | 34 (34.7) |
Progressive disease (PD) | 9 (19.4) |
Non-evaluable (NE) | 7 (7) |
Progression-Free Survival (PFS) | Overall Survival (OS) | |||||||
---|---|---|---|---|---|---|---|---|
Univariate | Multivariate | Univariate | Multivariate | |||||
Covariates | HR (95% CI) | p Value | HR (95% CI) | p Value | HR (95% CI) | p Value | HR (95% CI) | p Value |
Age (≥59 vs. <59 years) | 1.281 (0.823–1.994) | 0.273 | 1.800 (1.136–2.852) | 0.012 * | 2.071 (1.260–3.405) | 0.004 * | ||
Menopausal Status (post vs. pre) | 1.283 (0.606–2.713) | 0.515 | ||||||
Performance Status (2–3 vs. 1) | 2.142 (0.660–6.950) | 0.205 | 2.500 (0.773–8.082) | 0.126 | ||||
Histology | ||||||||
Mixed | Reference | Reference | ||||||
Ductal | 1.156 (0.421–3.174) | 0.778 | 0.782 (0.283–2.160) | 0.635 | ||||
Lobular | 1.691 (0.505–5.664) | 0.395 | 1.357 (0.417–4.420) | 0.612 | ||||
Stage at diagnosis (I-III vs. IV) | 1.492 (0.912–2.440) | 0.111 | 1.476 (0.881–2.470) | 0.139 | ||||
Molecular subtype of tumor | ||||||||
HER2+ | Reference | Reference | Reference | |||||
ER+ and/or PR+/HER2- | 1.635 (0.940–2.842) | 0.081 | 1.424 (0.807–2.513) | 0.222 | 1.625 (0.910–2.902) | 0.101 | ||
Triple negative | 2.447 (1.154–5.188) | 0.020 * | 2.397 (1.129–5.089) | 0.023 * | 1.7.57 (0.786–3.930) | 0.170 | ||
Visceral metastases (yes vs. no) | 1.091 (0.683–1.744) | 0.716 | 1.101 (0.666–1.818) | 0.708 | ||||
No. of disease sites (>2 vs. ≤2) | 1.274 (0.802–2.024) | 0.305 | 1.772 (1.102–2.849) | 0.018 * | 2.431 (1.451–4.073) | 0.001 * | ||
CTC detection (yes vs. no) | 1.987 (1.226–3.220) | 0.005 * | 1.922 (1.169–3.160) | 0.010 * | 1.343 (0.815–2.213) | 0.247 | ||
CTC phenotype | ||||||||
Fas+/FasL+ CTCs | 1.917 (1.165–3.154) | 0.010 * | 1.839 (1.107–3.055) | 0.019 * | 1.374 (0.814–2.320) | 0.234 | ||
Fas+ or FasL+ CTCs | 1.875 (0.813–4.326) | 0.140 | 1.320 (0.572–3.049) | 0.515 | ||||
Fas-/FasL- CTCs | 2.522 (0.607–10.485) | 0.203 | 3.486 (0.838–14.503) | 0.086 | ||||
PBMC phenotype | ||||||||
Fas-/FasL- PBMCs | Reference | Reference | Reference | |||||
Fas-/FasL+ PBMCs | 0.675 (0.226–2.020) | 0.483 | 0.357 (0.119–1.069) | 0.066 | 0.269 (0.119–1.069) | 0.024 | ||
Fas+/FasL+ PBMCs | 0.678 (0.243–1.890) | 0.458 | 0.234 (0.081–0.670) | 0.007 * | 0.161 (0.081–0.670) | 0.001 * |
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Papadaki, M.A.; Papadaki, E.; Chatziavraam, S.; Aggouraki, D.; Michaelidou, K.; Fotsitzoudis, C.; Vassilakopoulou, M.; Mavroudis, D.; Agelaki, S. Prognostic Value of Fas/Fas Ligand Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Patients with Metastatic Breast Cancer. Cancers 2024, 16, 2927. https://doi.org/10.3390/cancers16172927
Papadaki MA, Papadaki E, Chatziavraam S, Aggouraki D, Michaelidou K, Fotsitzoudis C, Vassilakopoulou M, Mavroudis D, Agelaki S. Prognostic Value of Fas/Fas Ligand Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Patients with Metastatic Breast Cancer. Cancers. 2024; 16(17):2927. https://doi.org/10.3390/cancers16172927
Chicago/Turabian StylePapadaki, Maria A., Eleni Papadaki, Sofia Chatziavraam, Despoina Aggouraki, Kleita Michaelidou, Charalampos Fotsitzoudis, Maria Vassilakopoulou, Dimitrios Mavroudis, and Sofia Agelaki. 2024. "Prognostic Value of Fas/Fas Ligand Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Patients with Metastatic Breast Cancer" Cancers 16, no. 17: 2927. https://doi.org/10.3390/cancers16172927