Identifying Subgroups With High Cardiovascular Risk in Breast Cancer Survivors (HARBOR)

October 28, 2016 updated by: The Netherlands Cancer Institute

HARBOR Study: Identifying Subgroups With High Cardiovascular Risk in Breast Cancer Survivors

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

628

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Recruiting
        • NKI-AVL
      • Groningen, Netherlands, 9713 GZ
        • Recruiting
        • UMCG

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Participants will be recruited from a large retrospective cohort of BC patients.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Anthracycline treated BC patients
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.
Procedure: 2D tissue doppler echocardiography
Other Names:
  • genetic analysis
  • quality of life assessment
  • laboratory biomarker analyses
  • vascular ultrasound
  • strain and strain rate parameters
  • questionnaire administration
  • anxiety and depression assessment
Anthracycline naive BC patients
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.
Procedure: 2D tissue doppler echocardiography
Other Names:
  • genetic analysis
  • quality of life assessment
  • laboratory biomarker analyses
  • vascular ultrasound
  • strain and strain rate parameters
  • questionnaire administration
  • anxiety and depression assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left ventricular ejection fraction
Time Frame: 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.
up to 12 years after breast cancer diagnosis

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diastolic cardiac function
Time Frame: 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.
up to 12 years after breast cancer diagnosis
Cardiac deformation
Time Frame: 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.
up to 12 years after breast cancer diagnosis
Biomarker assessment
Time Frame: 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.
up to 12 years after breast cancer diagnosis
Intima media thickness and arterial stiffness
Time Frame: 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.
up to 12 years after breast cancer diagnosis

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prospective evaluation of changes in LVEF, diastolic cardiac function, cardiac deformation, biomarkers levels, intima media thickness and arterial stiffness after two years in the same patients.
Time Frame: up to 14 years after breast cancer diagnosis
To compare each outcome of the first and second assessment separately in 1) every patient and 2) between patients treated with and without anthracyclines.
up to 14 years after breast cancer diagnosis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Netherlands Cancer Institute

Collaborators

University Medical Center Groningen

Investigators

  • Principal Investigator: Flora E. van Leeuwen, Prof. dr., The Netherlands Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2015

Primary Completion (Anticipated)

April 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

June 23, 2015

First Submitted That Met QC Criteria

June 25, 2015

First Posted (Estimate)

June 30, 2015

Study Record Updates

Last Update Posted (Estimate)

October 31, 2016

Last Update Submitted That Met QC Criteria

October 28, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL49405.031.14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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