Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting
Abstract
:1. Introduction
2. Results
2.1. Characteristics of Cohort
2.2. Comparison of Local versus Central Molecular-Like Subtyping
2.3. Distribution of Prosigna® Molecular Subtypes
2.4. Comparison between Surrogate Subtyping and Molecular Prosigna® Subtype
2.5. Prosigna® Risk Groups and Correlation with Local Surrogate Subtypes
2.6. Influence of Prosigna® Assay Result on Treatment Recommendation
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Molecular-Like Surrogate Subtyping
4.3. Prosigna® Assay
4.4. Statistical Analysis
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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Surrogate Subtypes | |||
---|---|---|---|
Luminal A-like | Luminal B-like HER2 negative | Luminal B-like HER2 positive | |
Local IHC subtyping | 35.4% | 64.6% | // |
Local IHC+G subtyping | 31.9% | 68.1% | // |
C1 IHC subtyping | 42.7% | 53.4% | 3.9% |
C1 IHC+G subtyping | 36.9% | 59.2% | 3.9% |
C6 IHC subtyping | 68.7% | 29.3% | 2.0% |
C6 IHC+G subtyping | 67.7% | 30.3% | 2.0% |
Luminal A-Like | Luminal B-Like | |||
---|---|---|---|---|
Match with Prosigna® Luminal A | Upgrade to Prosigna® Luminal B | Match with Prosigna® Luminal B | Downgrade to Prosigna® Luminal A | |
Local IHC subtyping | 82.5% (33/40) | 17.5% (7/40) | 58.9% (43/73) | 38.4% (28/73) |
Local IHC+G subtyping | 83.3% (30/36) | 16.7% (6/36) | 57.1% (44/77) | 40.3% (31/77) |
C1 IHC subtyping | 81.8% (36/44) | 18.2% (8/44) | 67.3% (37/55) | 30.9% (17/55) |
C1 IHC+G subtyping | 86.8% (33/38) | 13.2% (5/38) | 65.6% (40/61) | 32.8% (20/61) |
C6 IHC subtyping | 69.1% (47/68) | 30.9% (21/68) | 75.9% (22/29) | 24.1% (7/29) |
C6 IHC+G subtyping | 68.7% (46/67) | 31.3% (21/67) | 73.3% (22/30) | 26.7% (8/30) |
κ (IHC Subtype) | κ (IHC+G Subtype) | |
---|---|---|
Prosigna vs. local institutes | 0.374 | 0.344 |
Prosigna vs. center C1 | 0.449 | 0.455 |
Prosigna vs. center C6 | 0.379 | 0.36 |
Surrogate Subtype | Subgroup | ER | PR | HER2 | Ki-67 (%) | |
---|---|---|---|---|---|---|
Luminal A-like | + | +/− | − | and | Low (<20%) | |
Luminal B-like | HER2 negative | + | +/− | − | and | High (≥20%) |
HER2 positive | + | +/− | + | Any value | ||
HER2 positive (non-luminal) | − | − | + | Any value | ||
Triple negative | − | − | − | Any value |
Surrogate Subtype | Subgroup | ER | PR | HER2 | Tumor Grade | Ki-67 (%) | ||
---|---|---|---|---|---|---|---|---|
Luminal A-like | + | +/− | − | and | G1, G2 | or | Low (<20%) | |
Luminal B-like | HER2 negative | + | +/− | − | and | G3 | or | High (≥20%) |
HER2 positive | + | +/− | + | G1, G2, G3 | Any value | |||
HER2 positive (non-luminal) | − | − | + | G1, G2, G3 | Any value | |||
Triple negative | − | − | − | G1, G2, G3 | Any value |
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Erber, R.; Angeloni, M.; Stöhr, R.; Lux, M.P.; Ulbrich-Gebauer, D.; Pelz, E.; Bankfalvi, A.; Schmid, K.W.; Walter, R.F.H.; Vetter, M.; et al. Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting. Int. J. Mol. Sci. 2022, 23, 8716. https://doi.org/10.3390/ijms23158716
Erber R, Angeloni M, Stöhr R, Lux MP, Ulbrich-Gebauer D, Pelz E, Bankfalvi A, Schmid KW, Walter RFH, Vetter M, et al. Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting. International Journal of Molecular Sciences. 2022; 23(15):8716. https://doi.org/10.3390/ijms23158716
Chicago/Turabian StyleErber, Ramona, Miriam Angeloni, Robert Stöhr, Michael P. Lux, Daniel Ulbrich-Gebauer, Enrico Pelz, Agnes Bankfalvi, Kurt W. Schmid, Robert F. H. Walter, Martina Vetter, and et al. 2022. "Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting" International Journal of Molecular Sciences 23, no. 15: 8716. https://doi.org/10.3390/ijms23158716