Genomic Aberrations in Circulating Tumor DNAs from Palbociclib-Treated Metastatic Breast Cancer Patients Reveal a Novel Resistance Mechanism
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Plasma Separation
2.3. DNA Extraction
2.4. Targeted Gene Panel Sequencing
2.5. Somatic Mutation Calling
2.6. Statistical Analyses
3. Results
3.1. Patient Characteristics
3.2. Genomic Variants in cfDNAs at Baseline and Follow-Up
3.3. Identification of Significantly Mutated Genes at Progression by Paired Analyses
3.4. Acquired Mutations in Cell Cycle Pathway Genes
3.5. Acquired Mutations in Other Oncogenic Signaling Pathway Genes
3.6. Survival Analyses of Acquired Gene Mutations
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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No | Age (yr) | Race | ER/PR /HER2 | Tumor Differentiate | IBC | Lines of Previous Therapies * | Regimen | Number of Blood Samples | Response at EOT | TTP (wk) | |
---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | F/U | ||||||||||
1 | 54.56 | White | +/+/+ | Poorly | Yes | 6 | Palbociclib + TDM-1 | 1 | 1 (PD) | PD | 33.29 |
2 | 66.05 | Black | +/+/− | Poorly | No | 4 | Palbociclib + letrozole | 1 | 1 (PD) | PD | 18.86 |
3 | 33.03 | White | +/+/− | Poorly | Yes | 0 | Palbociclib + fulvestrant | 1 | 1 (PD) | PD | 8.00 |
4 | 42.79 | White | +/+/− | Moderately | No | 1 | Palbociclib + fulvestrant | 1 | 1 (PD) | PD | 11.14 |
5 | 39.42 | White | +/+/− | Poorly | No | 2 | Palbociclib + letrozole | 1 | 1 (PR) | PD | 51.00 |
6 | 58.14 | White | +/+/− | Moderately | No | 1 | Palbociclib + fulvestrant | 1 | 1 (SD), 1 (PD) | PD | 32.29 |
7 | 66.25 | White | +/+/− | Moderately | Yes | 3 | Palbociclib + fulvestrant | 1 | 1 (SD) | PD | 99.57 |
8 | 39.20 | White | +/−/− | Poorly | Yes | 8 | Palbociclib + letrozole | 1 | 1 (SD), 1 (PD) | PD | 25.29 |
9 | 54.87 | White | +/+/− | Unknown | Yes | 1 | Palbociclib + fulvestrant | 1 | 1 (SD) | SD (Side effects) | (12.14) |
10 | 32.56 | Black | +/+/− | Poorly | Yes | 1 | Palbociclib + letrozole | 1 | 1 (PR) | PR# (LTFU) | (70.86) |
11 | 51.12 | White | +/−/− | Poorly | Yes | 3 | Palbociclib + letrozole | 1 | 1 (PD) | PD | 13.00 |
12 | 74.81 | White | +/+/− | Moderately | No | 4 | Palbociclib + letrozole | 1 | 1 (PD) | PD | 39.57 |
13 | 45.15 | White | +/+/− | Poorly | Yes | 1 | Palbociclib + fulvestrant | 1 | 1 (PR) | PD | 37.14 |
14 | 64.12 | White | +/−/− | Moderately | No | 4 | Palbociclib + fulvestrant | 1 | 1 (PD) | PD | 22.14 |
15 | 58.62 | White | +/+/− | Poorly | Yes | 1 | Palbociclib + fulvestrant | 1 | 1 (PR) | PD | 82.29 |
16 | 63.78 | White | +/−/− | Moderately | No | 0 | Palbociclib + letrozole | 1 | 1 (SD), 1 (PD) | PD | 48.14 |
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Abu-Khalaf, M.; Wang, C.; Zhang, Z.; Luo, R.; Chong, W.; Silver, D.P.; Fellin, F.; Jaslow, R.; Lopez, A.; Cescon, T.; et al. Genomic Aberrations in Circulating Tumor DNAs from Palbociclib-Treated Metastatic Breast Cancer Patients Reveal a Novel Resistance Mechanism. Cancers 2022, 14, 2872. https://doi.org/10.3390/cancers14122872
Abu-Khalaf M, Wang C, Zhang Z, Luo R, Chong W, Silver DP, Fellin F, Jaslow R, Lopez A, Cescon T, et al. Genomic Aberrations in Circulating Tumor DNAs from Palbociclib-Treated Metastatic Breast Cancer Patients Reveal a Novel Resistance Mechanism. Cancers. 2022; 14(12):2872. https://doi.org/10.3390/cancers14122872
Chicago/Turabian StyleAbu-Khalaf, Maysa, Chun Wang, Zhenchao Zhang, Rui Luo, Weelic Chong, Daniel P. Silver, Frederick Fellin, Rebecca Jaslow, AnaMaria Lopez, Terrence Cescon, and et al. 2022. "Genomic Aberrations in Circulating Tumor DNAs from Palbociclib-Treated Metastatic Breast Cancer Patients Reveal a Novel Resistance Mechanism" Cancers 14, no. 12: 2872. https://doi.org/10.3390/cancers14122872