Heart Failure Association-International Cardio-Oncology Society Risk Score Validation in HER2-Positive Breast Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Data Collection
2.3. Risk Stratification
2.4. Study Outcomes and Definitions
2.5. Echocardiography
2.6. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Treatment Characteristics
3.3. CTRCT and Cardioprotective Therapies
3.4. HFA-ICOS Risk Score Performance
4. Discussion
Limitations
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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With Cardiotoxicity N (%) | Without Cardiotoxicity N (%) | Posterior Beta | 95% Credible Interval for Beta | |
---|---|---|---|---|
Characteristics | ||||
Age (>65 year/<65 year) | 5/18 (21.7) | 128/356 (26.4) | −0.319 | (−1.42, 0.63) |
Diabetes | 1/22 (4.3) | 22/440 (4.8) | −0.624 | (−3.8, 1.38) |
Hypertension | 10/13 (43.5) | 96/366 (20.8) | 1.055 | (0.171, 1.9) |
Kidney disease | 3/20 (13) | 28/434 (6.1) | 0.69 | (−0.83, 1.92) |
Congestive cardiac failure | 5 (1.3) | 12 (9) | ||
Smoking | 5/16 (23.8) | 101/331 (23.4) | −0.04 | (−1.19, 0.94) |
Death | 17/6 (73.9) | 253/230 (52.4) | 0.991 | (0.05, 2.01) |
Tumour Features | ||||
Grade 0 or 1 | 0 (5.3) | 31 (8.3) | - | - |
Grade 2 | 7 (36.9) | 176 (33.8) | 51.87 | (1.55, 215.14) |
Grade 3 | 16 (57.8) | 277 (57.9) | 52.28 | (1.99, 215.6) |
Previous trastuzumab | 22/1 (95.7) | 353/131 (72.9) | 2.5 | (0.62, 5.44) |
ER status (positive/negative) | 14/9 (59.4) | 288/193 (60.2) | −0.06 | (−0.94, 0.79) |
PgR status (positive/negative) | 11/12 (47.8) | 229/251 (47.7) | 0.003 | (−0.84, 0.85) |
Histology | ||||
Ductal | 313 (83.7) | 108 (81.2) | 0.45 | (−0.73, 1.94) |
Lobular | 1/22 (4.3) | 23/461 (4.8) | −0.62 | (−3.7, 1.36) |
Mixed | 0/23 (0) | 4/480 (0.8) | - | - |
Other | 2/21 (8.7) | 56/428 (11.6) | −0.541 | (−2.46, 0.85) |
Cardiac Therapy | ||||
Aspirin | 0 | 3/49 (0.6) | - | - |
Beta blockers | 0/23 (0) | 53/431 (0.8) | - | - |
Statins | 37 (9.9) | 48 (36.1) | 0.001 | |
Anticoagulant | 23/0 (100) | 432/48 (89.3) | 28.4 | (1.78, 118.88) |
ACE inhibitor | 0 | 4/48 (12) | - | - |
(A) | |||||
---|---|---|---|---|---|
Treatment Characteristic | Category | With Cardiotoxicity N (%) | Without Cardiotoxicity N (%) | Posterior Beta | 95% Credible Interval for Beta |
Concurrent chemotherapy | Paclitaxel; (yes/no) | 6/15 (28.6%) | 92/318 (22.4%) | 0.273 | (−0.8, 1.22) |
Docetaxel; (yes/no) | 14/7 (66.7%) | 226/168 (57.4%) | 0.41 | (−0.5, 1.35) | |
Anthracycline (Doxorubicin); (yes/no) | 0/23 (17.2%) | 39/445 (8.1%) | 0.86 | (−0.05, 1.73) | |
Carboplatin; (yes/no) | 7/14 (33.3%) | 160/233 (40.7%) | −0.432 | (−3.6, 1.6) | |
Epirubicin | - | 2 (0.5%) | 0 (0 %) | - | - |
Pertuzumab (yes/no) | - | 1/22 (4.1%) | 20/464 (4.3%) | −0.08 | (−0.98, 1.99) |
Radiotherapy (yes/no) | - | 15/6 (65.2%) | 313/104 (64.7%) | −0.12 | (−1.08, 0.95) |
Endocrine therapy | Tamoxifen (yes/no) | 8/15 (34.8%) | 127/357 (26.2%) | 0.376 | (−0.51, 1.25) |
Letrozole (yes/no) | 10/13 (43.5%) | 132/352 (27.3%) | 0.704 | (−0.16, 1.55) | |
Other Aromatase inhibitors (yes/no) | 1/22 (4.3%) | 40/444 (8.3%) | −1.2 | (−4.23, 0.73) | |
(B) | |||||
Treatment Characteristic | Category | Low Risk (N = 100) | Medium Risk (N = 301) | High Risk (N = 90) | Very High Risk (N = 16) |
Concurrent chemotherapy | Paclitaxel; (yes/no) | 13 (13%) | 59 (19.6%) | 20 (22.2%) | 6 (37.5%) |
Docetaxel; (yes/no) | 55 (55%) | 146 (48.5%) | 34 (37.8%) | 5 (31.3%) | |
Anthracycline (Doxorubicin); (yes/no) | 12 (13%) | 51 (17%) | 19 (21.1%) | 5 (31.3%) | |
Carboplatin; (yes/no) | 36 (36%) | 108 (35.9%) | 18 (20%) | 5 (31.3%) | |
Epirubicin use | Yes | 2 (2%) | 0 (0%) | 0 (0%) | 0 (0%) |
No | 78 (78%) | 260 (86.4%) | 78 (86.7%) | 14 (87.5%) | |
Pertuzumab use | Yes | 3 (3%) | 17 (5.6%) | 1 (1.1%) | 0 (0%) |
No | 97 (97%) | 284 (94.4%) | 89 (98.9%) | 16 (100%) | |
Radiotherapy use | Yes | 60 (60%) | 199 (66.1%) | 57 (63.3%) | 12 (75%) |
No | 22 (22%) | 64 (21.3%) | 22 (24.4%) | 2 (12.5%) | |
Unknown | 18 (18%) | 38 (12.6%) | 11 (12.2%) | 2 (12.5%) | |
Endocrine use | None | 25 (25%) | 113 (37.5%) | 42 (46.7%) | 5 (31.3%) |
Tamoxifen | 31 (31%) | 80 (26.6%) | 22 (24.4%) | 2 (12.5%) | |
Letrozole | 30 (30%) | 83 (27.6%) | 23 (25.6%) | 6 (37.5%) | |
Other aromatase inhibitors | 9 (9%) | 21 (7%) | 9 (10%) | 2 (12.5%) |
Cardiac Events | Overall (N = 507) | Age < 65 Years (N = 374) | Age ≥ 65 Years (N = 133) | Beta (95% CrI) | Low Risk (N = 100) | Medium Risk (N = 301) | High Risk (N = 90) | Very High Risk (N = 16) |
---|---|---|---|---|---|---|---|---|
Overall: N (%) | 27 (5.3%) | 19 (3.7%) | 8 (1.6%) | −0.13 (−0.97, 0.78) | 3 (3%) | 12 (3.98%) | 6 (4.5%) | 6 (37.5%) |
Not related to cancer treatment: N (%) | 4 (0.8%) | 1 (0.2%) | 3 (0.6%) | - | 0 | 2 (0.7%) | 2 (0.7%) | 0 |
Related to cancer treatment: N (%) | 23 (4.5%) | 18 (3.6%) | 5 (1%) | 0.33 (−0.63, 1.47) | 3 (3%) | 10 (3.3%) | 4 (4.4%) | 6 (37.5%) |
LVEF decline ≥10%: N (%) | 7 (1.4%) | 6 (1.2%) | 1 (0.2%) | 1.16 (−0.87, 4.11) | 0 | 3 (1%) | 1 (1.1%) | 3 (18.8%) |
LVEF decline below 50%: N (%) | 14 (2.8%) | 13 (2.6%) | 1 (0.2%) | 1.97 (0.08, 4.85) | 1 (1%) | 8 (2.7%) | 2 (2.2%) | 3 (18.8%) |
LVEF decline ≥10%/below 50%: N (%) | 14 (2.8%) | 13 (2.6%) | 1 (0.2%) | 1.94 (0.03, 4.89) | 1 (1%) | 8 (2.7%) | 2 (2.2%) | 3 (18.8%) |
Congestive heart failure: N (%) | 9 (1.8%) | 5 (1%) | 4 (0.8%) | −0.77 (−2.12, 0.64) | 2 (2%) | 2 (0.7%) | 2 (2.2%) | 3 (18.8%) |
Diastolic dysfunction: N (%) | 4 (0.8%) | 2 (0.4%) | 2 (0.4%) | 0.44 (−1.83, 3.45) | 1 (1%) | 1 (0.7%) | 2 (2.2%) | 0 |
Death due to cardiotoxicity: N (%) | 2 (0.4%) | 2 (0.4%) | 0 (0%) | −0.77 (−3.82, 2.43) | 0 | 0 | 1 (1.1%) | 1 (6.3%) |
Treatment Characteristic Category | Overall (N = 507) | Age < 65 Years (N = 374) | Age ≥ 65 Years (N = 133) | p-Value | Low Risk (N = 100) | Medium Risk (N = 301) | High Risk (N = 90) | Very High Risk (N = 16) | p-Value |
---|---|---|---|---|---|---|---|---|---|
(ACEi/ARB) | 4 (0.8%) | 1 (0.3%) | 3 (2.3%) | 0.002 | 0 (0%) | 4 (1.3%) | 0 (0%) | 0 (0%) | 0.12 |
Alpha blocker | 2 (0.4%) | 1 (0.3%) | 1 (0.8%) | 0.070 | 0 (0%) | 2 (0.7%) | 0 (0%) | 0 (0%) | 0.13 |
Beta blocker | 4 (0.8%) | 3 (0.8%) | 1 (0.8%) | 0.19 | 2 (2%) | 2 (0.7%) | 0 (0%) | 0 (0%) | 0.078 |
Statins | 5 (1%) | 1 (0.3%) | 4 (3%) | 0.001 | 0 (0%) | 5 (1.7%) | 0 (0%) | 0 (0%) | 0.13 |
CCB | 2 (0.4%) | 1 (0.3%) | 1 (0.8%) | 0.085 | 0 (0%) | 2 (0.7%) | 0 (0%) | 0 (0%) | 0.32 |
Aspirin | 3 (0.6%) | 1 (0.3%) | 2 (1.5%) | 0.001 | 0 (0%) | 2 (0.7%) | 1 (1.1%) | 0 (0%) | 0.20 |
Diuretic | 2 (0.4%) | 0 (0%) | 2 (1.5%) | 0.007 | 0 (0%) | 1 (0.3%) | 1 (1.1%) | 0 (0%) | 0.079 |
Cardiac Events | Sensitivity | Specificity | AUC, 95% CI | PPV | NPV | Accuracy |
---|---|---|---|---|---|---|
Overall | 0.26 | 0.97 | 0.652 (0.53, 0.76) | 0.113 | 0.963 | 0.785 |
Related to cancer treatment | 0.26 | 0.98 | 0.643 (0.51, 0.76) | 0.375 | 0.965 | 0.947 |
LVEF decline ≥10% | 0.42 | 0.974 | 0.762 (0.55, 0.97) | 0.188 | 0.992 | 0.966 |
LVEF decline below 50% | 0.214 | 0.973 | 0.629 (0.47, 0.78) | 0.188 | 0.978 | 0.953 |
LVEF decline ≥10%/below 50% | 0.214 | 0.974 | 0.629 (0.47, 0.78) | 0.188 | 0.978 | 0.953 |
CHF | 0.55 | 0.79 | 0.658 (0.46, 0.85) | 0.047 | 0.99 | 0.793 |
Diastolic dysfunction | 0.50 | 0.79 | 0.588 (0.29, 0.88) | 0.019 | 0.995 | 0.791 |
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Cronin, M.; Crowley, A.; Davey, M.G.; Ryan, P.; Abdelshafy, M.; Elkoumy, A.; Elzomor, H.; Arsang-Jang, S.; Ganly, S.; Nash, P.; et al. Heart Failure Association-International Cardio-Oncology Society Risk Score Validation in HER2-Positive Breast Cancer. J. Clin. Med. 2023, 12, 1278. https://doi.org/10.3390/jcm12041278
Cronin M, Crowley A, Davey MG, Ryan P, Abdelshafy M, Elkoumy A, Elzomor H, Arsang-Jang S, Ganly S, Nash P, et al. Heart Failure Association-International Cardio-Oncology Society Risk Score Validation in HER2-Positive Breast Cancer. Journal of Clinical Medicine. 2023; 12(4):1278. https://doi.org/10.3390/jcm12041278
Chicago/Turabian StyleCronin, Michael, Aileen Crowley, Matthew G. Davey, Peter Ryan, Mahmoud Abdelshafy, Ahmed Elkoumy, Hesham Elzomor, Shahram Arsang-Jang, Sandra Ganly, Patrick Nash, and et al. 2023. "Heart Failure Association-International Cardio-Oncology Society Risk Score Validation in HER2-Positive Breast Cancer" Journal of Clinical Medicine 12, no. 4: 1278. https://doi.org/10.3390/jcm12041278
APA StyleCronin, M., Crowley, A., Davey, M. G., Ryan, P., Abdelshafy, M., Elkoumy, A., Elzomor, H., Arsang-Jang, S., Ganly, S., Nash, P., Crowley, J., Sharif, F., Simpkin, A., Lowery, A., Wijns, W., Kerin, M., & Soliman, O. (2023). Heart Failure Association-International Cardio-Oncology Society Risk Score Validation in HER2-Positive Breast Cancer. Journal of Clinical Medicine, 12(4), 1278. https://doi.org/10.3390/jcm12041278