Circulating Tumor Cell Clusters Are Frequently Detected in Women with Early-Stage Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Comparison of Different Strategies for CTC-Cluster Identification
2.1.1. Technical Validation of Approaches used for CTC-Cluster Detection
2.1.2. CTC-Cluster Detection in Clinical Samples Using an Epithelial-Based and a Size-Based Approach
2.2. Detection of CTC-Clusters by a Size-Based Approach in Patients with Breast Cancer
2.2.1. Patient Characteristics
2.2.2. CTC-Clusters in Patients with Metastatic and Early Breast Cancer
2.2.3. Longitudinal Evaluation of CTC-Clusters during Neoadjuvant Therapy
3. Discussion
4. Materials and Methods
4.1. Cell Cultures and Spiking Experiments
4.2. Comparison of CellSearch® and CellSieve™ Filters for CTC-Cluster Detection in Clinical Samples
4.3. Case Series & Blood Sample Collection Timing
4.4. Patho-Biological Characterization of Tumors
4.5. CTC-Cluster Enumeration by ScreenCell® Filters
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Sample ID | Enrichment Technology | Mammosphere Recovery Rate (%) |
---|---|---|
1 | CellSearch® | 70 |
2 | 80 | |
3 | 60 | |
4 | CellSieve™ | 70 |
5 | 80 | |
6 | 60 | |
7 | ScreenCell® | 60 |
8 | 100 | |
9 * | 100 | |
10 * | 100 |
N | % | Median CTC-Clusters (Range) | p | CTC-Cluster + (%) | p | |
---|---|---|---|---|---|---|
Age | ||||||
• <50 | 20 | 54.1 | 2.5 (0–20) | 0.889 | 15 (75%) | 0.719 |
• ≥50 | 17 | 45.9 | 2 (0–20) | 11 (65%) | ||
Tumor size | ||||||
• T1–T2 | 21 | 56.8 | 4 (0–20) | 0.180 | 16 (76%) | 0.475 |
• ≥T3 | 16 | 43.2 | 1 (0–15) | 10 (63%) | ||
Nodal status | ||||||
• N0 | 8 | 21.6 | 0 (0–12) | 0.273 | 3 (37.5) | 0.123 |
• N1 | 21 | 56.8 | 3 (0–20) | 17 (81.1) | ||
• ≥N2 | 8 | 21.6 | 3 (0–20) | 6 (75%) | ||
Histology | ||||||
• NST | 35 | 94.6 | 2 (0–20) | 0.322 | 15(68%) | |
• Lobular | 2 | 5.4 | 3 (0–15) | 11(73%) | >0.99 | |
Grade | ||||||
• 2 | 10 | 27.0 | 2 (0–15) | 0.918 | 7 (70%) | >0.99 |
• 3 | 22 | 59.5 | 1.5 (0–20) | 15 (68.2%) | ||
• Missing | 5 | 13.5 | ||||
Ki67 | ||||||
• <20 | 4 | 10.8 | 1.5 (0–12) | >0.10 | 2 (50%) | 0.570 |
• ≥20 | 32 | 86.5 | 2 (0–20) | 23 (72%) | ||
• Missing | 1 | 2.7 | - | - | ||
Subtype | ||||||
• HER2-positive | 11 | 29.7 | 0 (0–8) | 0.047 | 5 (45%) | 0.111 |
• Triple negative | 11 | 29.7 | 5 (0–20) | 9 (82%) | ||
• Luminal-like | 15 | 40.5 | 4 (0–20) | 12 (80%) | ||
Type of neoadjuvant chemotherapy | ||||||
• Anthra/Taxane | 32 | 86.5 | 2.5 (0–20) | 0.984 | 22 (69%) | 0.609 |
• CarboPt-based | 5 | 13.5 | 1 (0–20) | 4 (80%) |
N | % | |
---|---|---|
Age | ||
• <50 | 5 | 21.7 |
• ≥50 | 18 | 78.3 |
Histology | ||
• Ductal | 15 | 65.2 |
• Lobular | 2 | 8.7 |
• Other | 6 | 26.1 |
Disease type at screening | ||
• Visceral | 6 | 26.1 |
• Nonvisceral | 12 | 52.2 |
• Missing | 3 | 13.0 |
Hormone receptor status | ||
• ER -positive, PgR positive or both | 18 | 78.3 |
• ER-negative and PgR-negative | 5 | 21.7 |
HER2 status | ||
• Positive | 1 | 4.3 |
• Negative | 22 | 95.7 |
Metastatic disease at diagnosis | ||
• No | 15 | 65.2 |
• Yes | 8 | 34.8 |
Prior chemotherapy for metastatic disease | ||
• No | 20 | 87.0 |
• Yes | 3 | 13.0 |
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Reduzzi, C.; Di Cosimo, S.; Gerratana, L.; Motta, R.; Martinetti, A.; Vingiani, A.; D’Amico, P.; Zhang, Y.; Vismara, M.; Depretto, C.; et al. Circulating Tumor Cell Clusters Are Frequently Detected in Women with Early-Stage Breast Cancer. Cancers 2021, 13, 2356. https://doi.org/10.3390/cancers13102356
Reduzzi C, Di Cosimo S, Gerratana L, Motta R, Martinetti A, Vingiani A, D’Amico P, Zhang Y, Vismara M, Depretto C, et al. Circulating Tumor Cell Clusters Are Frequently Detected in Women with Early-Stage Breast Cancer. Cancers. 2021; 13(10):2356. https://doi.org/10.3390/cancers13102356
Chicago/Turabian StyleReduzzi, Carolina, Serena Di Cosimo, Lorenzo Gerratana, Rosita Motta, Antonia Martinetti, Andrea Vingiani, Paolo D’Amico, Youbin Zhang, Marta Vismara, Catherine Depretto, and et al. 2021. "Circulating Tumor Cell Clusters Are Frequently Detected in Women with Early-Stage Breast Cancer" Cancers 13, no. 10: 2356. https://doi.org/10.3390/cancers13102356