Dataset Information

Association of hospital and physician case volumes with cardiac monitoring and cardiotoxicity during adjuvant trastuzumab treatment for breast cancer: a retrospective cohort study.

ABSTRACT:

Background

Adjuvant trastuzumab is the standard of care for patients with HER2 overexpressing breast cancer, but use of trastuzumab may lead to cardiotoxicity. Our goal was to evaluate the relationship between hospital and physician case volume and cardiac outcomes in this population.

Methods

In this retrospective cohort study, we identified all female patients in Ontario with a breast cancer diagnosis in 2003-2009 who underwent treatment with trastuzumab through a provincial drug-funding program and linked these patients to administrative databases to ascertain patient demographics, treating hospital and physician characteristics, admissions to hospital, cardiac risk factors, cardiac imaging and comorbidities. Insufficient cardiac monitoring was defined as per the Canadian Trastuzumab Working Group guideline. Cardiotoxicity was defined as receiving fewer than 16 of 18 doses of trastuzumab because of heart failure admission, heart failure diagnosis or discontinuation of the drug after cardiac imaging. We constructed hierarchical multivariable logistic regression models to evaluate the effect of annual hospital volume, cumulative physician volume and treatment period on cardiac monitoring and cardiotoxicity.

Results

Of 3777 women treated by 214 oncologists at 68 hospitals, 918 (24.3%) had insufficient cardiac monitoring and cardiotoxicity developed in 640 (16.9%). Cardiotoxicity occurred in 389 (42.4%) and 251 (8.8%) patients in the insufficient- and sufficient-monitoring groups, respectively. Higher annual hospital and cumulative physician volumes, and more recent calendar period, were all independent predictors for decreased cardiotoxicity. Adjustment for rates of cardiac monitoring annulled the relationships between case volume and cardiotoxicity.

Interpretation

Greater hospital and physician case volumes are associated with reduced rates of trastuzumab-related cardiotoxicity, most likely because of better cardiac monitoring at higher volume centres.

SUBMITTER: Chin-Yee NJ

PROVIDER: S-EPMC4866921 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:PurposePatients treated with adjuvant trastuzumab require adequate cardiac monitoring. We describe the patterns of cardiac monitoring and evaluate factors associated with adequate monitoring in a large population-based study of older patients with breast cancer.Patients and methodsPatients age 66 years or older with full Medicare coverage, diagnosed with stage I to III breast cancer between 2005 and 2009, and treated with adjuvant trastuzumab-based chemotherapy were identified in the SEER-Medicare and the Texas Cancer Registry-Medicare databases. The adequacy of cardiac monitoring was determined. Chemotherapy, trastuzumab use, cardiac monitoring, and comorbidities were identified by using International Classification of Diseases, 9th revision and Healthcare Common Procedure Coding System codes. Prescribing physician characteristics were also evaluated. Analyses included descriptive statistics and multilevel logistic regression models.ResultsIn all, 2,203 patients were identified; median age was 72 years. Adequate monitoring was identified in only 36.0% of the patients (n = 793). In the multivariable model, factors associated with optimal cardiac monitoring included a more recent year of diagnosis (hazard ratio [HR], 1.83; 95% CI, 1.32 to 2.54), anthracycline use (HR, 1.39; 95% CI, 1.14 to 1.71), female prescribing physician (HR, 1.37; 95% CI, 1.10 to 1.70), and physician graduating after 1990 (HR, 1.66; 95% CI, 1.29 to 2.12). The presence of cardiac comorbidities was not a determinant for cardiac monitoring. Of the variance in the adequacy of cardiac monitoring, 15.3% was attributable to physician factors and 5.2% to measured patient factors.ConclusionA large proportion of patients had suboptimal cardiac monitoring. Physician characteristics had more influence than measured patient-level factors in the adequacy of cardiac monitoring. Because trastuzumab-related cardiotoxicity is reversible, efforts to improve the adequacy of cardiac monitoring are needed, particularly in vulnerable populations.

Project description:OBJECTIVES:This study sought to determine the rate of chemotherapy-related cardiotoxicity and to estimate adherence to recommendations for cardiac monitoring among breast cancer patients treated with chemotherapy. BACKGROUND:Heart failure (HF) is a known complication associated with cancer therapies. Little is known regarding the rate of chemotherapy-related cardiotoxicity and adherence to recommendations for cardiac monitoring among chemotherapy-treated breast cancer patients. METHODS:Patients >18 years of age with a diagnosis of nonmetastatic invasive breast cancer between 2009 and 2014, treated with chemotherapy within 6 months of their diagnosis, were identified in the Truven Health MarketScan (IBM Watson Health, Cambridge, Massachusetts) database. HF, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics, Cox proportional hazard regression, and logistic regression. RESULTS:A total of 16,456 patients were included; the median age was 56 years old. Cardiotoxicity was identified in 4.2% of patients. Therapy with trastuzumab (hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.72 to 2.36) and anthracyclines (HR: 1.53; 95% CI: 1.30 to 1.80), Deyo comorbidity scores (HR: 1.38; 95% CI: 1.15 to 1.66; HR: 2.47; 95% CI: 1.94 to 3.15 for scores of 1 and ?2, respectively), hypertension (HR: 1.28, 95% CI: 1.09 to 1.51), and valve disease (HR: 1.93; 95% CI: 1.48 to 2.51) were associated with an increased risk of cardiotoxicity. Patients ?35 years of age (HR: 0.37; 95% CI: 0.19 to 0.72) and 36 to 49 years of age (HR: 0.49; 95% CI: 0.38 to 0.62) were less likely to have cardiotoxicity than patients 65 years of age and older. Among 4,325 patients treated with trastuzumab, guideline-adherent cardiac monitoring was identified in 46.2% of patients. Therapies using anthracyclines (odds ratio [OR]: 1.58; 95% CI: 1.35 to 1.87), taxanes (OR: 1.63; 95% CI: 1.27 to 2.08), and radiation (OR: 1.22; 95% CI: 1.08 to 1.39) were associated with guideline-adherent monitoring. CONCLUSIONS:HF is an uncommon complication of breast cancer therapies. The risk was higher among patients treated with trastuzumab or anthracyclines and lower in younger patients. Cardiac monitoring among trastuzumab-treated patients should be a priority among high-risk patients and in the presence of comorbidities or other chemotherapies such as those using anthracyclines.

Project description:AimsAn improved understanding of the pathophysiology of trastuzumab-mediated cardiotoxicity is required to improve outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We aimed to characterize the cardiac and cardiometabolic phenotype of trastuzumab-mediated toxicity and potential interactions with cardiac pharmacotherapy.Methods and resultsThis study was an analysis of serial magnetic resonance imaging (MRI) and circulating biomarker data acquired from patients with HER2-positive early-stage breast cancer participating in a randomized-controlled clinical trial for the pharmaco-prevention of trastuzumab-associated cardiotoxicity. Circulating biomarkers (B-type natriuretic peptide, troponin I, MMP-2 and -9, GDF-15, neuregulin-1, and IGF-1) and MRI of cardiac structure and function and abdominal fat distribution were acquired prior to trastuzumab, post-cycle 4 and post-cycle 17. Ninety-four participants (51 ± 8 years) completed the study with 30 on placebo, 33 on perindopril, and 31 on bisoprolol. Post-cycle 4, global longitudinal strain deteriorated from baseline in both placebo (+2.0 ± 2.7%, P = 0.002) and perindopril (+0.9 ± 2.5%, P = 0.04), but not with bisoprolol (-0.2 ± 2.1%, P = 0.55). In all groups combined, extracellular volume fraction and GDF-15 increased post-cycle 4 (+1.3 ± 4.4%, P = 0.004; +130 ± 150%, P ≤ 0.001, respectively). However, no significant change in troponin I was detected throughout trastuzumab. In all groups combined, visceral and intermuscular fat volume increased post-cycle 4 (+7 ± 17%, P = 0.02, +8 ± 23%, P = 0.02, respectively), while muscle volume and IGF-1 decreased from post-cycle 4 to 17 (-2 ± 10%, P = 0.008, -18 ± 28%, P < 0.001, respectively).ConclusionTrastuzumab results in impaired cardiac function and early myocardial inflammation. Trastuzumab is also associated with deleterious changes to the cardiometabolic phenotype which may contribute to the increased cardiovascular risk in this population.