Original Study| Volume 23, ISSUE 1, P23-31, January 2023

ABSDELL Model: Development and Internal Validation of a Risk Prediction Model of LVEF Decline in Breast Cancer Patients Treated With Trastuzumab

Published:October 22, 2022DOI:


      • Previous prediction models include only baseline factors, which do not allow for real-time prediction of trastuzumab-induced cardiotoxicity.
      • Utilizing a single center retrospective observational cohort, we conducted model development and internal validation using a machine learning algorithm.
      • An integrated model, called the ABSDELL model based on 7 risk factors including age, BMI, SBP, DBP, E-wave, LVESD and LVEF, has been established to assist clinicians in adjusting monitoring strategies and detecting cardiotoxicity early based on up-to-date information gathered during follow-up.



      This study aims to establish an integrated model for predicting trastuzumab-associated decline of Left ventricular ejection fraction (LVEF) during drug administration.


      A retrospective study of 212 women who diagnosed with HER2-positive breast cancer and treated with chemotherapy and trastuzumab was conducted. Medical records were collected from 6 months before staring trastuzumab to 3 years afterwards. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to select variables, time-dependent receiver operating characteristic (ROC) curve and calibration plots were used to evaluate the model. The adjusted C-index and Brier scores were calculated using a bootstrap internal validation procedure.


      The median age of participants is 53.2 years old. The median length of follow-up was 336 days. There were 72 patients (33.96%) whose LVEF declined ≥ 10% (10 absolute percent points). Seven factors, namely age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), mitral peak E-wave velocity (E-wave), left ventricular end-systolic diameter (LVESD) and LVEF, were selected. The name of the ABSDELL model was formed by the initials of each predictor. The area under the curve (AUC) of the model was 0.802 in 1 year and 0.881 in 3 years. Calibration plots indicate the predicted and actual probabilities were highly consistent. In the internal validation, 1-year and 3-year adjusted C-index was 0.801 and 0.881, and adjusted Brier score was 0.118 and 0.091, separately.


      The ABSDELL model can effectively predicts the probability of LVEF decline in breast cancer patients treated with trastuzumab.



      A-wave (mitral peak A-wave velocity), BMI (body mass index), CKMB (creatine kinase isoenzyme-MB), DBP (diastolic blood pressure), eGFR (estimated glomerular filtration rate), Em (mitral annulus e' velocity), E-wave (mitral peak E-wave velocity), GLS (global longitudinal strain), HER2 (the human epidermal growth factor receptor 2), HF (heart failure), HGB (hemoglobin), HDL-C (high-density lipoprotein cholesterol), Hs-TnT (high-sensitive troponin T), LAA (left atrial area), LAD (left atrial diameter), LAP (left atrial pressure), LAVI (left atrial volume index), LDL-C (low-density lipoprotein cholesterol), LVEDD (left ventricular end-diastolic diameter), LVEF (left ventricular ejection fraction), LVESD (left ventricular end-systolic diameter), NT-proBNP (N-terminal pro-brain natriuretic peptide), RAA (right atrial area), SBP (systolic blood pressure), Scr (serum creatinine), Sm (mitral annulus s’ velocity), sST2 (soluble ST2), TCHO (total cholesterol), TG (triglyceride), TRV (tricuspid valve regurgitation velocity)
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        • Shelburne N
        • Adhikari B
        • Brell J
        • et al.
        Cancer treatment-related cardiotoxicity: current state of knowledge and future research priorities.
        J Natl Cancer Inst. 2014; 106
        • Miller KD
        • Nogueira L
        • Mariotto AB
        • et al.
        Cancer treatment and survivorship statistics, 2019.
        CA Cancer J Clin. 2019; 69: 363-385
        • Wolff AC
        • Hammond MEH
        • Hicks DG
        • et al.
        Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American society of clinical oncology/college of American pathologists clinical practice guideline update.
        J Clin Oncol. 2013; 31: 3997-4013
        • Smith I
        • Procter M
        • Gelber RD
        • et al.
        2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial.
        The Lancet. 2007; 369 (2007/01/06/): 29-36
        • Cote GM
        • Sawyer DB
        • Chabner BA.
        ERBB2 inhibition and heart failure.
        N Engl J Med. 2012; 367: 2150-2153
        • Cardinale D
        • Colombo A
        • Torrisi R
        • et al.
        Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation.
        J Clin Oncol. 2010; 28: 3910-3916
        • Plana JC
        • Galderisi M
        • Barac A
        • et al.
        Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American society of echocardiography and the European association of cardiovascular imaging.
        Eur Heart J Cardiovasc Imaging. 2014; 15: 1063-1093
        • Battisti NML
        • Andres MS
        • Lee KA
        • et al.
        Incidence of cardiotoxicity and validation of the heart failure association-international cardio-oncology society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer.
        Breast Cancer Res Treat. 2021; 188: 149-163
        • Ewer MS
        • Vooletich MT
        • Durand JB
        • et al.
        Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment.
        J Clin Oncol. 2005; 23: 7820-7826
      1. Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131:1981-8. doi:10.1161/circulationaha.114.013777.

        • Romond EH
        • Jeong JH
        • Rastogi P
        • et al.
        Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer.
        J Clin Oncol. 2012; 30: 3792-3799
        • Ezaz G
        • Long JB
        • Gross CP
        • Chen J.
        Risk prediction model for heart failure and cardiomyopathy after adjuvant trastuzumab therapy for breast cancer.
        J Am Heart Assoc. 2014; 3e000472
        • Lyon AR
        • Dent S
        • Stanway S
        • et al.
        Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-oncology study group of the heart failure association of the European society of cardiology in collaboration with the international cardio-oncology society.
        Eur J Heart Fail. 2020; 22: 1945-1960
        • Jiang Z
        • Song E
        • Wang X
        • et al.
        Guidelines of Chinese Society of Clinical Oncology (CSCO) on diagnosis and treatment of breast cancer (2020 version).
        Translational Breast Cancer Res. 2020; 1: 2-6
        • Guglin M
        • Krischer J
        • Tamura R
        • et al.
        Randomized trial of lisinopril versus carvedilol to prevent trastuzumab cardiotoxicity in patients with breast cancer.
        J Am Coll Cardiol. 2019; 73: 2859-2868
        • Abdel-Qadir H
        • Thavendiranathan P
        • Austin PC
        • et al.
        Development and validation of a multivariable prediction model for major adverse cardiovascular events after early stage breast cancer: a population-based cohort study.
        Eur Heart J. 2019; 40: 3913-3920
        • Chavez-MacGregor M
        • Niu J
        • Zhang N
        • et al.
        Cardiac monitoring during adjuvant trastuzumab-based chemotherapy among older patients with breast cancer.
        J Clin Oncol. 2015; 33: 2176-2183
        • Zamorano JL
        • Lancellotti P
        • Rodriguez Muñoz D
        • et al.
        2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for practice guidelines: the task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC).
        Eur Heart J. 2016; 37: 2768-2801
        • Peduzzi P
        • Concato J
        • Kemper E
        • Holford TR
        • Feinstein AR.
        A simulation study of the number of events per variable in logistic regression analysis.
        J Clin Epidemiol. 1996; 49: 1373-1379
        • Jalali A
        • Alvarez-Iglesias A
        • Roshan D
        • Newell J.
        Visualising statistical models using dynamic nomograms.
        PLoS One. 2019; 14e0225253
      2. Moons KG, Kengne AP, Woodward M, et al. Risk prediction models: I. Development, internal validation, and assessing the incremental value of a new (bio)marker. Heart. 2012;98:683-90. doi:10.1136/heartjnl-2011-301246.

        • Collins GS
        • Reitsma JB
        • Altman DG
        • Moons KG.
        Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement.
        Bmj. 2015; 350: g7594
        • Moons KGM
        • Wolff RF
        • Riley RD
        • et al.
        PROBAST: A tool to assess risk of bias and applicability of prediction model studies: explanation and elaboration.
        Ann Intern Med. 2019; 170: W1-W33
        • Mele D
        • Malagutti P
        • Indelli M
        • et al.
        Reversibility of left ventricle longitudinal strain alterations induced by adjuvant therapy in early breast cancer patients.
        Ultrasound Med Biol. 2016; 42: 125-132
        • Curigliano G
        • Lenihan D
        • Fradley M
        • et al.
        Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.
        Ann Oncol. 2020; 31: 171-190
        • Dobson R
        • Ghosh AK
        • Ky B
        • et al.
        British society for echocardiography and British cardio-oncology society guideline for transthoracic echocardiographic assessment of adult cancer patients receiving anthracyclines and/or trastuzumab.
        Echo Res Pract. 2021; 8: G1-G18
        • Čelutkienė J
        • Pudil R
        • López-Fernández T
        • et al.
        Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC).
        Eur J Heart Fail. 2020; 22: 1504-1524
      3. Robinson S, Rana B, Oxborough D, et al. A practical guideline for performing a comprehensive transthoracic echocardiogram in adults: the British Society of Echocardiography minimum dataset. Echo Res Pract. 2020;7:G59-G93. doi:10.1530/erp-20-0026.

        • Nagueh SF
        • Smiseth OA
        • Appleton CP
        • et al.
        Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American society of echocardiography and the European association of cardiovascular imaging.
        J Am Soc Echocardiogr. 2016; 29: 277-314
        • Pelà G
        • Regolisti G
        • Coghi P
        • et al.
        Effects of the reduction of preload on left and right ventricular myocardial velocities analyzed by Doppler tissue echocardiography in healthy subjects.
        Eur J Echocardiogr. 2004; 5: 262-271
        • Yu CM
        • Sanderson JE
        • Marwick TH
        • Oh JK.
        Tissue Doppler imaging a new prognosticator for cardiovascular diseases.
        J Am Coll Cardiol. 2007; 49: 1903-1914
        • Dovancescu S
        • Pellicori P
        • Mabote T
        • Torabi A
        • Clark AL
        • Cleland JGF.
        The effects of short-term omission of daily medication on the pathophysiology of heart failure.
        Eur J Heart Fail. 2017; 19: 643-649
      4. Seko Y, Kato T, Haruna T, et al. Association between atrial fibrillation, atrial enlargement, and left ventricular geometric remodeling. Sci Rep. 2018;8:6366. doi:10.1038/s41598-018-24875-1.

        • Kim EK
        • Cho J
        • Kim JY
        • et al.
        Early decline in left ventricular ejection fraction can predict trastuzumab-related cardiotoxicity in patients with breast cancer: a study using 13 years of registry data.
        Cancer Res Treat. 2019; 51: 727-736
        • Ben Kridis W
        • Sghaier S
        • Charfeddine S
        • et al.
        A Prospective study about trastuzumab-induced cardiotoxicity in HER2-positive breast cancer.
        Am J Clin Oncol. 2020; 43: 510-516