BRENDA-Score, a Highly Significant, Internally and Externally Validated Prognostic Marker for Metastatic Recurrence: Analysis of 10,449 Primary Breast Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Surrogate Definition of Intrinsic Subtypes
4. Statistical Analysis
5. Results
6. External Validation
7. Discussion
8. Conclusions
- (1).
- The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients;
- (2).
- It is based on routine parameters, easily accessible in daily clinical care;
- (3).
- The BRENDA-Score is stable over at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar with AUCs between 0.76 and 0.81;
- (4).
- Internal and external validations confirmed these results;
- (5).
- Finally, the BRENDA-Score is in addition a good prognostic marker for overall survival. This confirms that metastatic free survival is a strong surrogate parameter for overall survival;
- (6).
- A multivariate Cox regression model for overall survival with BRENDA- and Nottingham prognostic score (NPS) showed that only the BRENDA-Score is statistically significant.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Brenda-Score | |||||||
---|---|---|---|---|---|---|---|
Total | Very Low Risk | Low Risk | Intermediate Risk | High Risk | Very High Risk | ||
n = 8566 (%) | n = 2568 (30.0) | n = 2661 (31.1) | n = 1718 (20.1) | n = 817 (9.5) | n = 802 (9.4) | Sig | |
62.1 ± 13.1 min 18; max 89 | 62.1 ± 13.1 min 18; max 89 | 61.5 ± 13.2 min 24; max 89 | 62.6 ± 14.0 min 27; max 89 | 62.9 ± 13.7 min 18; max 89 | 0.005 | ||
T1 | 4842 (56.5) | 2568 (100) | 1616 (60.7) | 428 (24.9) | 178 (21.8) | 52 (6.5) | <0.001 |
T2 | 3281 (38.3) | 0 (0) | 988 (37.1) | 1192 (69.4) | 606 (74.2) | 495 (61.7) | |
T3/T4 | 443 (5.2) | 0 (0) | 57 (2.1) | 98 (5.7) | 33 (4.0) | 443 (5.2) | |
nodal negative | 5272 (61.5) | 2569 (100) | 2063 (77.5) | 626 (36.4) | 15 (1.8) | 0 (0) | <0.001 |
1–3 affected lymph nodes | 1974 (23.0) | 0 (0) | 598 (22.5) | 903 (52.6) | 362 (44.3) | 111 (13.8) | |
>3 affected lymph nodes | 1320 (15.4) | 0 (0) | 0 (0) | 189 (11.0) | 440 (53.9) | 691 (86.2) | |
G1 | 817 (9.5) | 539 (21.0) | 228 (8.6) | 7 (0.9) | 7 (0.9) | 1 (0.1) | <0.001 |
G2 | 5303 (61.9) | 2029 (79.0) | 1755 (66.0) | 367 (44.9) | 367 (44.9) | 187 (23.3) | |
G3 | 2446 (28.6) | 0 (0) | 678 (25.5) | 443 (54.2) | 443 (54.2) | 614 (76.6) | |
luminal A | 5305 (61.9) | 2552 (99.4) | 1559 (58.6) | 790 (46.0) | 316 (38.7) | 88 (11.0) | <0.001 |
luminal B-HER2-negative like | 1185 (13.8) | 0 (0) | 315 (11.8) | 353 (20.5) | 268 (32.8) | 249 (31.0) | |
Luminal B-HER2-positive like | 870 (10.2) | 16 (0.6) | 377 (14.2) | 236 (13.7) | 95 (11.6) | 146 (18.2) | |
HER2 overexpressing | 410 (4.8) | 0 (0) | 126 (4.7) | 109 (6.3) | 60 (7.3) | 115 (14.3) | |
Triple-negative | 796 (9.3) | 0 (0) | 284 (10.7) | 230 (13.4) | 78 (9.5) | 204 (25.4) |
Variables in the Equation | ||||||
---|---|---|---|---|---|---|
Covariates | B | SE | Sig. | HR | 95% Confidence Interval | |
lower | upper | |||||
luminal B-HER2-negative like | 0.48 | 0.18 | 0.007 | 1.61 | 1.14 | 2.28 |
Luminal B-HER2-positive like | 0.42 | 0.15 | 0.004 | 1.53 | 1.14 | 2.04 |
HER2 overexpressing | 0.72 | 0.18 | 0.000 | 2.06 | 1.45 | 2.94 |
Triple-negative | 0.76 | 0.17 | 0.000 | 2.14 | 1.55 | 2.96 |
T2 | 0.50 | 0.09 | 0.000 | 1.65 | 1.38 | 1.97 |
T3/T4 | 0.96 | 0.14 | 0.000 | 2.62 | 2.01 | 3.41 |
G2 | 0.49 | 0.24 | 0.038 | 1.64 | 1.03 | 2.61 |
G3 | 0.63 | 0.27 | 0.020 | 1.89 | 1.10 | 3.22 |
1 ≤ n ≤3 | 0.80 | 0.11 | 0.000 | 2.23 | 1.81 | 2.74 |
n > 3 | 1.56 | 0.10 | 0.000 | 4.75 | 3.89 | 5.79 |
Bootstrap for Variables in the Equation | ||||||
---|---|---|---|---|---|---|
B | Bootstrap a | |||||
Bias | Std. Error | Sig. (2-Tailed) | 95% Confidence Interval | |||
lower | upper | |||||
luminal B-HER2-negative like | 0.48 | 0.01 | 0.18 | 0.010 | 0.11 | 0.83 |
Luminal B-HER2-positive like | 0.42 | −0.01 | 0.15 | 0.005 | 0.09 | 0.70 |
HER2 overexpressing | 0.72 | −0.01 | 0.18 | 0.001 | 0.36 | 1.05 |
Triple-negative | 0.76 | 0.00 | 0.17 | 0.001 | 0.42 | 1.07 |
T2 | 0.50 | 0.00 | 0.09 | 0.001 | 0.32 | 0.69 |
T3/T4 | 0.96 | −0.01 | 0.14 | 0.001 | 0.66 | 1.22 |
G2 | 0.49 | 0.03 | 0.25 | 0.034 | 0.09 | 1.08 |
G3 | 0.63 | 0.02 | 0.28 | 0.014 | 0.14 | 1.23 |
1≤ n≤ 3 | 0.80 | 0.00 | 0.10 | 0.001 | 0.60 | 1.00 |
n > 3 | 1.56 | 0.00 | 0.11 | 0.001 | 1.35 | 1.78 |
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Wischnewsky, M.; Schwentner, L.; Diessner, J.; de Gregorio, A.; Joukhadar, R.; Davut, D.; Salmen, J.; Bekes, I.; Kiesel, M.; Müller-Reiter, M.; et al. BRENDA-Score, a Highly Significant, Internally and Externally Validated Prognostic Marker for Metastatic Recurrence: Analysis of 10,449 Primary Breast Cancer Patients. Cancers 2021, 13, 3121. https://doi.org/10.3390/cancers13133121
Wischnewsky M, Schwentner L, Diessner J, de Gregorio A, Joukhadar R, Davut D, Salmen J, Bekes I, Kiesel M, Müller-Reiter M, et al. BRENDA-Score, a Highly Significant, Internally and Externally Validated Prognostic Marker for Metastatic Recurrence: Analysis of 10,449 Primary Breast Cancer Patients. Cancers. 2021; 13(13):3121. https://doi.org/10.3390/cancers13133121
Chicago/Turabian StyleWischnewsky, Manfred, Lukas Schwentner, Joachim Diessner, Amelie de Gregorio, Ralf Joukhadar, Dayan Davut, Jessica Salmen, Inga Bekes, Matthias Kiesel, Max Müller-Reiter, and et al. 2021. "BRENDA-Score, a Highly Significant, Internally and Externally Validated Prognostic Marker for Metastatic Recurrence: Analysis of 10,449 Primary Breast Cancer Patients" Cancers 13, no. 13: 3121. https://doi.org/10.3390/cancers13133121