Identifying Subgroups With High Cardiovascular Risk in Breast Cancer Survivors

• Conditions: Breast Neoplasms; Cardiovascular Diseases
• Interventions: Procedure: 2D tissue doppler echocardiography

• Registration Number: NCT02485626
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

The purpose of this study is to evaluate the prevalence of (sub)clinical cardiovascular disease, cardiovascular risk factors and metabolic abnormalities among long-term breast cancer survivors treated with or without anthracyclines in order to identify patients at increased risk of developing cardiovascular disease.

Detailed Description

Rationale: Breast cancer (BC) incidence is increasing, while mortality from BC is decreasing. Since the life expectancy of BC patients is improving, the evaluation of treatment-associated cardiovascular disease (CVD) in BC survivors is becoming increasingly important. An excess risk of CVD, mainly due to coronary heart disease (CHD), has been observed after radiotherapy (RT) as administered in the 1960s-1980s. Anthracycline-containing CT and trastuzumab are known to induce cardiotoxicity, especially congestive heart failure (CHF). However, the long-term risks of CVD after anthracycline-containing CT, trastuzumab, hormonal therapy (HT) and contemporary RT techniques have hardly been examined. Furthermore, the potential interaction of these treatment modalities has not been well addressed, and there is limited knowledge about the contribution of classic cardiovascular risk factors and the metabolic syndrome to risk and severity of treatment-associated CVD in BC survivors.

Objectives: • to evaluate the prevalence of (sub)clinical CVD, cardiovascular risk factors and metabolic abnormalities among BC survivors treated with and without anthracyclines in two groups at (a) 5 - 7 years and (b) 10 - 12 years after diagnosis;

• to prospectively evaluate changes in prevalence of (sub)clinical CVD, cardiovascular risk factors and metabolic abnormalities after two years in the same patients.

Secondary objectives are to evaluate the predictive role of newly developed markers for CVD and to evaluate the effects of other BC treatment modalities, psychosocial outcomes, endocrine function and menopausal status on the risk of developing (sub)clinical CVD.

Study design: multicenter (AVL and UMCG) cross-sectional cohort study with prospective monitoring of the same cohort.

Study population: female BC survivors treated with and without anthracyclines 5 - 7 and 10 - 12 years ago at the AVL or UMCG, aged 40-50 years at time of therapy.

Main study parameter: the difference in (sub)clinical cardiovascular damage between patients treated with and without anthracyclines, as measured by left ventricular function parameters.

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2015-06-23
• Study First Submitted QC: 2015-06-25
• Study First Posted: 2015-06-30
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-28
• Last Update Posted: 2016-10-31
• Primary Completion: 2019-04
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 628

Inclusion Criteria

• early invasive BC (TNM stage I - III);
• diagnosed and/or treated in the AVL or UMCG;
• treated 5 - 7 years or 10 - 12 years ago;
• aged 40-50 years at time of therapy;
• signed written informed consent.

Exclusion Criteria

• history of RT or CT unrelated to BC;
• current treatment for BC recurrence or second malignancy (including contralateral BC) with the exception of non-melanoma skin cancer or curatively treated carcinoma in situ of the cervix;
• history of cardiac disease (CHF, acute coronary syndrome, coronary revascularization procedure, symptomatic valvular dysfunction, cardiomyopathy or congenital heart defect) before diagnosis and treatment for BC;
• mental disability or psychological condition potentially hampering compliance with the study protocol;
• insufficient understanding of the Dutch language.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Anthracycline treated BC patients	2D tissue doppler echocardiography	AVL or UMCG patients between the age of 40 - 50 at the time of BC diagnosis and treatment, treated with anthracyclines respectively 5-7 years ago and 10-12 years ago.
Anthracycline naive BC patients	2D tissue doppler echocardiography	AVL or UMCG patients between the age of 40 - 50 at the time of BC diagnosis and treatment, treated without anthracyclines respectively 5-7 years ago and 10-12 years ago.

Primary Outcome Measures

Name	Time	Method
Left ventricular ejection fraction	up to 12 years after breast cancer diagnosis	The main study parameter will be the difference in left ventricular ejection fraction between patients treated with and without anthracyclines.

Secondary Outcome Measures

Name	Time	Method
Biomarker assessment	up to 12 years after breast cancer diagnosis	To compare levels of several (candidate) cardiovascular biomarkers (NT-proBNP, hs-TnT, CRP) in patients treated with and without anthracyclines.
Intima media thickness and arterial stiffness	up to 12 years after breast cancer diagnosis	To compare intima media thcikness and arterial stiffness as measured by vascular ultrasound in patients treated with and without anthracyclines.
Diastolic cardiac function	up to 12 years after breast cancer diagnosis	To compare diastolic cardiac function as measured by tissue doppler echocardiography (E/e' and E/A ratio) in patients treated with and without anthracyclines.
Cardiac deformation	up to 12 years after breast cancer diagnosis	To compare cardiac deformation as measured by speckle tracking imaging (global longitudial strain, radial strain and circumferential strain) in patients treated with and without anthracyclines.

Trial Locations

Locations (2)

UMCG; 🇳🇱 Groningen, Netherlands

NKI-AVL; 🇳🇱 Amsterdam, Netherlands