Breast Cancer Long-term Outcomes on Cardiac Functioning: a Longitudinal Study (BLOC-II)

Rationale: In addition to surgery, effective breast cancer (BC) treatment typically requires chemotherapy, radiotherapy, or both. However, it is still unclear whether patients with BC are at increased risk of long-term cardiac dysfunction due to the adverse effects of these therapies. In a cross-sectional study in primary care, a comparison on cardiac dysfunction between 350 BC survivors and 350 age- and general practitioner (GP)- matched controls without cancer was made. In that study, BC survivors were at increased risk of mild systolic cardiac dysfunction (left ventricle ejection fraction (LVEF)< 54%). By contrast, there was no significant difference in an LVEF < 50% or in diastolic dysfunction. To date it remains uncertain whether the mild or subclinical dysfunction we observed predicts further cardiac deterioration. Consequently, the translation of these results into guidelines for the daily practice of the GP is unclear.

Objective: The aim of the here proposed study is to clarify whether cardiac function in survivors of BC should be monitored by GPs, by assessing whether an unselected population of long-term BC survivors is at increased risk of developing cardiac dysfunction, whether in this group at-risk subgroups exists, and what factors are associated with the highest risk.

Study design: A new assessment of cardiac function among women included in the BLOC-I study. This produces a longitudinal matched cohort design consisting of two cohorts in primary care.

Study population: Survivors of BC, diagnosed ≥11 years ago who received chemotherapy and/or radiotherapy, and a matched reference population with no history of cancer. All participants participated in the Breast cancer Long-term Outcome of Cardiac function (BLOC-I) study.

Main study parameters/endpoints: Left ventricular systolic dysfunction. Systolic cardiac dysfunction is defined as a LVEF <54/50/45%.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Ventricular Dysfunction; Cardiotoxicity; Neoplasm, Breast
• Intervention / Treatment: Diagnostic test: Echocardiography

• Study Type: Observational
• Enrollment (Anticipated): 455

Contacts and Locations

• Study Contact: Name: Daan Brandenbarg, PhD; Phone Number: 0031628475305; Email: d.brandenbarg@umcg.nl
• Study Contact Backup: Name: Laurine T van der Wal, MSc; Phone Number: 0031503616154; Email: l.t.van.der.wal@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9700 AD
    • Recruiting
    • University Medical Center Groningen
    • Contact: Laurine T van der Wal, MSc; Phone Number: 0031503616154; Email: l.t.van.der.wal@umcg.nl
    • Principal Investigator: Daan Brandenbarg, PhD
    • Sub-Investigator: Laurine T van der Wal, MSc
    • Sub-Investigator: Saskia WMC Maass, PhD
    • Principal Investigator: Jourik A Gietema, Prof. dr.
    • Principal Investigator: Peter van der Meer, Prof. dr.
    • Principal Investigator: Geertruida H de Bock, Prof. dr.
    • Principal Investigator: Marjolein Y Berger, Prof. dr.
    • Sub-Investigator: Anne PG Crijns, PhD
    • Sub-Investigator: Michiel R de Boer, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

BC survivors were matched with women of the same age (±1 year) who had the same GP, but who had no history of cancer or cancer treatment (chemotherapy or radiotherapy).

A longitudinal matched cohort design consisting of two cohorts in primary care: one with survivors of BC, diagnosed ≥11 years ago who received chemotherapy and/or radiotherapy, and one with a matched reference population with no history of cancer.

Description

Inclusion Criteria:

• Patients who previously took part in de BLOC-I study will be included. These criteria were:
• females diagnosed with stage I-III BC at least five years ago or local or locoregional recurrence of BC at least five years ago
• treatment with chemotherapy and/or radiotherapy.

Exclusion Criteria:

• Patients unfit to travel to the hospital due to severe mental or physical illness, based on assessment by their GP.

Exclusion criteria for the BC survivors in the BLOC-I study were:

• metastatic disease at the time of BC diagnosis;
• BC treatment after 80 years of age;
• history of treatment for other types of cancer.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Breast cancer survivors; Survivors of BC, diagnosed ≥11 years ago, who received chemotherapy and/or radiotherapy	Diagnostic test: Echocardiography; During echocardiography, the following parameters will be assessed: Dimensions; Left ventricle function; Right ventricle function; Valves: Aorta valve and pulmonic valve; Other findings such as: frequency, rhythm, quality
Reference population; Age and GP matched reference population without a history of cancer	Diagnostic test: Echocardiography; During echocardiography, the following parameters will be assessed: Dimensions; Left ventricle function; Right ventricle function; Valves: Aorta valve and pulmonic valve; Other findings such as: frequency, rhythm, quality

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular systolic dysfunction	Prevalance of systolic cardiac dysfunction defined as a LVEF <54%	through study completion (from Ocotober 2022 - December 2024)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically used LVEF cut-off points <45% and <50%	Prevalance of systolic cardiac dysfunction defined as a LVEF <45% and <50%	through study completion (from Ocotober 2022 - December 2024)
Course of cardiac function	Rate of change of systolic and diastolic cardiac function by change in LVEF	through study completion (from Ocotober 2022 - December 2024)
Cardiovascular diseases	Prevalence of cardiovascular diseases obtained from electronic patient records	through study completion (from Ocotober 2022 - December 2024)
Symptoms of hearth failure	Clinical symptoms of heart failure measured using a self-constructed questionnaire	through study completion (from Ocotober 2022 - December 2024)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient characteristics	age, BMI, menopausal state	through study completion (from Ocotober 2022 - December 2024)
Physical activity	Changes in Physical Acticity measured with Short Questionnaire to Assess Health-enhancing physical activity (SQUASH)	through study completion (from Ocotober 2022 - December 2024)
Depression	Symptoms of depression measured with Hospital Anxiety and Depression Scale - Despression (HADS-D)	through study completion (from Ocotober 2022 - December 2024)
Anxiety	Symptoms of anxiety measured with Hospital Anxiety and Depression Scale - Anxiety (HADS-A)	through study completion (from Ocotober 2022 - December 2024)
Fatigue	Multidimensional assessment of fatigue mesaured with Multidimensional Fatigue Index - 20 (MFI-20).	through study completion (from Ocotober 2022 - December 2024)
Use of cardiovascular medication	Use of cardiovascular medication based on electronic patient records	through study completion (from Ocotober 2022 - December 2024)
Smoking behavior (self-reported pack years)	Smoking behavior	through study completion (from Ocotober 2022 - December 2024)

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development

Publications and helpful links

General Publications

• Boerman LM, Maass SWMC, van der Meer P, Gietema JA, Maduro JH, Hummel YM, Berger MY, de Bock GH, Berendsen AJ. Long-term outcome of cardiac function in a population-based cohort of breast cancer survivors: A cross-sectional study. Eur J Cancer. 2017 Aug;81:56-65. doi: 10.1016/j.ejca.2017.05.013. Epub 2017 Jun 8.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Heart failure; Breast cancer; Cardiotoxicity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Wounds and Injuries; Breast Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Heart Failure; Breast Neoplasms; Cardiotoxicity; Ventricular Dysfunction
• Other Study ID Numbers: 202100903

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No