Targeted-Gene Sequencing to Catch Triple Negative Breast Cancer Heterogeneity before and after Neoadjuvant Chemotherapy
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Somatic Mutations in TNBC Samples
2.3. Genes and Pathways Associated with pCR
2.4. Comparison between Pre- and Post-NAC Samples
2.5. Tumor-Infiltrating Lymphocytes
3. Discussion
4. Materials and Methods
4.1. Patient Cohort
4.2. Targeted Next Generation Sequencing
4.3. Sequencing and Bio-Informatic Data Analysis
4.4. Statistical Analysis for Association of Genomic and Clinical Data
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristics | N (%) |
---|---|
Patient age | |
<50 years | 12 (63) |
≥50 years | 7 (37) |
Clinical T size | |
2–5 cm | 13 (68) |
>5 cm | 6 (32) |
Clinical nodal status | |
N0 | 8 (42) |
N1-3 | 11 (58) |
Clinical stage | |
IIA | 5 (26) |
IIB | 10 (53) |
IIIA | 2 (11) |
IIIB | 1 (5) |
IIIC * | 1 (5) |
Tumor grade | |
G2 | 1 (5) |
G3 | 18 (95) |
Ki67 | |
<30% | 3 (16) |
≥30% <60% | 3 (16) |
≥60% | 12 (63) |
Missing | 1 (5) |
Type of NAC | |
– Doxorubicin/Paclitaxel every 3 weeks followed by CMF1–8 every 4 weeks ^ | 11 (58) |
– Doxorubicin/Paclitaxel every 3 weeks followed by Eribulin 1–8 every 3 weeks ^^ | 5 (26) |
– Other | 3 (16) |
Path Findings | |
pCR | |
ypT0N0 | 4 (21) |
Residual Disease | |
ypT1N0 | 6 (32) |
ypT2-3N0 | 7 (37) |
ypT2N1 | 1 (5) |
ypT4N3 | 1 (5) |
Evaluable Cases | |
Pre-NAC | 16 (84) |
Post-NAC | 15 (79) |
Paired pre- and post-NAC | 12 (63) |
Events | |
Distant metastases | 7 (37) |
Patient | Cluster | No. of Genes in Cluster | No. of Genes in Cluster Mutated in POST-NAC Tumor | Enriched Pathways Including Genes Mutated in POST-NAC Tumor |
---|---|---|---|---|
p5 | C1 | 42 | 1 | No pathways found |
C2 | 10 | 1 | No pathways found | |
C3 | 15 | 0 | NA | |
p10 | C1 | 3 | 3 | EGFR tyrosine kinase inhibitor resistance (KEGG - hsa01521); Ras signaling pathway (KEGG - hsa04014) |
C2 | 3 | 0 | NA | |
p11 | C1 | 3 | 2 | Negative regulation of cell cycle process (GO:0010948); Androgen receptor signaling pathway (GO:0030521) |
C2 | 5 | 2 | Ras signaling pathway (hsa04014); TOR signaling (GO:0031929); EGFR tyrosine kinase inhibitor resistance (KEGG - hsa01521) | |
p12 | C1 | 3 | 3 | mTOR signaling pathway (KEGG - hsa04150); PI3K-Akt signaling pathway (KEGG - hsa04151); |
C2 | 2 | 0 | NA | |
p13 | C1 | 1 | 1 | PI3K-Akt signaling pathway (KEGG - hsa04151); Negative regulation of cell cycle process (GO:0010948) |
C2 | 4 | 2 | TORC1 signaling (GO:0038202) | |
p16 | C1 | 11 | 0 | NA |
C2 | 3 | 3 | Hippo signaling pathway (KEGG - hsa04390) | |
C3 | 4 | 0 | NA | |
p18 | C1 | 2 | 2 | Regulation of cell cycle arrest (GO:0071156); PI3K-Akt signaling pathway (KEGG - hsa04151) |
C2 | 2 | 2 | Mismatch repair (KEGG - hsa03430); Platinum drug resistance (KEGG - hsa01524) | |
C3 | 2 | 0 | NA |
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Di Cosimo, S.; Appierto, V.; Silvestri, M.; Pruneri, G.; Vingiani, A.; Perrone, F.; Busico, A.; Folli, S.; Scaperrotta, G.; de Braud, F.G.; et al. Targeted-Gene Sequencing to Catch Triple Negative Breast Cancer Heterogeneity before and after Neoadjuvant Chemotherapy. Cancers 2019, 11, 1753. https://doi.org/10.3390/cancers11111753
Di Cosimo S, Appierto V, Silvestri M, Pruneri G, Vingiani A, Perrone F, Busico A, Folli S, Scaperrotta G, de Braud FG, et al. Targeted-Gene Sequencing to Catch Triple Negative Breast Cancer Heterogeneity before and after Neoadjuvant Chemotherapy. Cancers. 2019; 11(11):1753. https://doi.org/10.3390/cancers11111753
Chicago/Turabian StyleDi Cosimo, Serena, Valentina Appierto, Marco Silvestri, Giancarlo Pruneri, Andrea Vingiani, Federica Perrone, Adele Busico, Secondo Folli, Gianfranco Scaperrotta, Filippo Guglielmo de Braud, and et al. 2019. "Targeted-Gene Sequencing to Catch Triple Negative Breast Cancer Heterogeneity before and after Neoadjuvant Chemotherapy" Cancers 11, no. 11: 1753. https://doi.org/10.3390/cancers11111753