Breast NeoplasmsHARBORNCT02485626
Identifying Subgroups With High Cardiovascular Risk in Breast Cancer Survivors
An observational study of Breast Neoplasms and Cardiovascular Diseases, run by The Netherlands Cancer Institute at 2 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 50 years, women only
- Conditions the study is for
- Breast Neoplasms, Cardiovascular Diseases
- What is being tested?
- 2D tissue doppler echocardiography
- Type of treatment
- Surgery or procedure
- How many people
- 628 participants
- Where
- 2 sitesNetherlands
- Study dates
- Apr 2015to Dec 2019
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 50 years
- Women only
- No healthy volunteers
- Adult
Study population: Participants will be recruited from a large retrospective cohort of BC patients.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Flora E. van Leeuwen, Prof. dr. contact
Jourik A. Gietema, Prof. dr. contact
Netherlands2 sites, 2 recruiting
- Recruiting
NKI-AVL
Amsterdam, 1066 CX
- Recruiting
UMCG
Groningen, 9713 GZ
About this study
Official title: 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.
Read the 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.
- Conditions
- Breast Neoplasms, Cardiovascular Diseases
- Being tested
- 2D tissue doppler echocardiography
- Keywords
- Anthracyclines
- Medical subject headings
- Breast Neoplasms, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2D tissue doppler echocardiographyProcedure or surgery
Also called laboratory biomarker analyses, vascular ultrasound, strain and strain rate parameters, genetic analysis
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: 2D tissue doppler echocardiography | |
| 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. Receives: Procedure: 2D tissue doppler echocardiography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular ejection fraction
The main study parameter will be the difference in left ventricular ejection fraction between patients treated with and without anthracyclines.
Measured: up to 12 years after breast cancer diagnosis
Secondary outcomes (4)
Diastolic cardiac function
To compare diastolic cardiac function as measured by tissue doppler echocardiography (E/e' and E/A ratio) in patients treated with and without anthracyclines.
Measured: up to 12 years after breast cancer diagnosis
Cardiac deformation
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.
Measured: up to 12 years after breast cancer diagnosis
Biomarker assessment
To compare levels of several (candidate) cardiovascular biomarkers (NT-proBNP, hs-TnT, CRP) in patients treated with and without anthracyclines.
Measured: up to 12 years after breast cancer diagnosis
Intima media thickness and arterial stiffness
To compare intima media thcikness and arterial stiffness as measured by vascular ultrasound in patients treated with and without anthracyclines.
Measured: up to 12 years after breast cancer diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2015 (estimated)
- Study startApr 2015
- Primary completionApr 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 628 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen
- Responsible party
- Sponsor
- Investigators
- Flora E. van Leeuwen, Prof. dr., Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02485626
- Sponsor's protocol ID
- NL49405.031.14
- Acronym
- HARBOR
- Status last verified
- Oct 2016
- First submitted
- 23 Jun 2015
- Last updated
- 31 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
van Ommen-Nijhof A, Jacobse JN, Steggink LC, Lefrandt JD, Gietema JA, van Leeuwen FE, Schaapveld M, Sonke GS. Adjuvant aromatase inhibitor therapy and early markers for cardiovascular disease in breast cancer survivors. Breast Cancer Res Treat. 2022 Dec;196(3):591-602. doi: 10.1007/s10549-022-06714-0. Epub 2022 Oct 1.
PubMed 36181605
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HARBOR Study: Identifying Subgroups With High Cardiovascular Risk in Breast Cancer Survivors
- ClinicalTrials.gov ID
- NCT02485626
- Acronym / sponsor ID
- HARBOR / NL49405.031.14
- Conditions
- Breast Neoplasms, Cardiovascular Diseases
- Keywords
- Anthracyclines
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 628 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- University Medical Center Groningen
- Study start
- Apr 2015
- Primary completion
- Apr 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 30 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Target follow-up
- 2 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anthracycline treated BC patients | – | Procedure: 2D tissue doppler echocardiographyAVL 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 | – | Procedure: 2D tissue doppler echocardiographyAVL 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. |
Who may qualify
- Ages
- 40 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Participants will be recruited from a large retrospective cohort of BC patients.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 2D tissue doppler echocardiographyAlso: laboratory biomarker analyses, vascular ultrasound, strain and strain rate parameters, genetic analysis | Procedure or surgery | Anthracycline naive BC patients, Anthracycline treated BC patients |
Primary outcome
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.
4 secondary outcomes
Diastolic cardiac function
Time frame: up to 12 years after breast cancer diagnosis
Cardiac deformation
Time frame: up to 12 years after breast cancer diagnosis
Biomarker assessment
Time frame: up to 12 years after breast cancer diagnosis
Intima media thickness and arterial stiffness
Time frame: up to 12 years after breast cancer diagnosis
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2016.
- Derived from this study: PubMed 36181605van Ommen-Nijhof A, Jacobse JN, Steggink LC, Lefrandt JD, Gietema JA, van Leeuwen FE, Schaapveld M, Sonke GS. Adjuvant aromatase inhibitor therapy and early markers for cardiovascular disease in breast cancer survivors. Breast Cancer Res Treat. 2022 Dec;196(3):591-602. doi: 10.1007/s10549-022-06714-0. Epub 2022 Oct 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flora E. van Leeuwen, Prof. dr. contact
Jourik A. Gietema, Prof. dr. contact
Flora E. van Leeuwen, Prof. dr. principal investigator
The Netherlands Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Neoplasms and Cardiovascular Diseases, run by The Netherlands Cancer Institute at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 31 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Flora E. van Leeuwen, Prof. dr. (f.v.leeuwen@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left ventricular ejection fraction (time frame: up to 12 years after breast cancer diagnosis). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02485626, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2016.