Plain English Summary
Background and study aims
Due to the improvement in survival time of breast cancer survivors, the long term effects of anti-cancer (antineoplastic) treatments are becoming increasingly apparent in this group. One of the most serious and significant effects of these treatments is cardiotoxicity (damage to the heart muscle), which can lead to cardiovascular health complications. Therefore, physical exercise is widely recommended as a supporting therapy for cancer and heart rehabilitation.
This study aims to look at the effects of supervised physical exercise on cardiotoxicity and cardiac health in women with breast cancer during antineoplastic treatment. It also aims to examine the effects of physical exercise on physical functionality, quality of life, fatigue and peripheral neuropathy (weakness, numbness and pain in the hands and feet as a result of nerve damage).
Who can participate?
Adult women with breast cancer (stage IA-IIIC) undergoing a neo/adjuvant anthracycline-containing chemotherapy or trastuzumab scheme.
What does the study involve?
Participants will be randomly allocated to either the intervention group or the control group. The intervention group will be asked to participate in a supervised physical exercise program for two months, which will involve aerobic exercise and resistance training, with a progressive increase in volume and intensity. The control group will not receive any exercise program. Before and after the exercise program, measurements will be taken, including blood pressure, heart rate and biomarkers, along with various questionnaires. After the final set of measurements are taken, participants in the control group will then be offered the exercise program received by the intervention group. Additionally, 24 hours before the end of each treatment cycle, blood samples will be taken from all participants.
What are the possible benefits and risks of participating?
Participants may feel the benefits derived from the supervised physical exercise such as prevention of cardiac dysfunction, improvement of cardiac health, improved physical fitness, improved quality of life, and reduced fatigue, peripheral neuropathy and pain. The possible risksof participating in the study are fractures (from exercise), lymphedema (swelling in the arms and legs), hot flushes and extra fatigue.
Where is the study run from?
Centro Hospitalar Vila Nova de Gaia/Espinho (Portugal)
When is the study starting and how long is it expected to run for?
December 2018 to December 2022
Who is funding the study?
Centro Hospitalar de Vila Nova de Gaia/Espinho, Universidade da Beira Interior e Associação de Investigação de Cuidados de Suporte em Oncologia (Portugal)
Who is the main contact?
1. Mr. Pedro Antunes (firstname.lastname@example.org)
2. Dr. Ana Joaquim (email@example.com)
Mr Pedro Antunes
Rua Mateus Fernandes Lote 5 nº37 1C
Dr Ana Joaquim
Rua Rio do Vake nº560
Effects of supervised physical exercise on cardiotoxicity and cardiac health in women breast cancer survivors during anthracycline-containing chemotherapy or trastuzumab: a randomised controlled trial
We anticipate that performing physical exercise during anthracycline-containing chemotherapy or trastuzumab will be associated with:
1. Attenuation of subclinical cardiotoxicity markers, such as systolic function (left ventricular ejection fraction), myocardial deformation (global longitudinal strain), and circulating cardiac biomarkers
2. Attenuation of cardiopulmonary capacity reduction
3. Control of cardiac health parameters, such as: blood pressure, resting heart, resting heart rate variability, and recovery heart rate
The present study was submitted to the ethics committee of the Centro Hospitalar de Vila Nova de Gaia/Espinho. We expect to obtain its ethical approval by the end of October
Interventional randomised controlled trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
No participant information sheet available
Patients will be randomised to either the intervention or the control group using a permutated block design with random four and six block sizes.
Patients in the intervention group will perform a supervised physical exercise program specifically developed for BC patients, based on the guidelines of the American College of Sports Medicine and a close cooperation between physical sports technicians and medical staff. The physical program comprises 3 weekly sessions, oriented in small groups (3-5 patients), supervised by the main author. Each session will involve an initial warm-up (5 min) followed by strength muscle and aerobic training (60 min) and ending with a cooldown phase (5 min).
During the intervention period, patients allocated to the control group will receive only the usual supportive care.
There will be a 3 month follow-up period.
Primary outcome measure
1. Cardiotoxicity markers:
1.1. Systolic function (left ventricular ejection fraction), assessed using standard transthoracic echocardiography at the baseline, at the end of treatment and 3 months afterwards
1.2. Myocardial deformation (global longitudinal strain), assessed using standard transthoracic echocardiography at the baseline, at the end of treatment and 3 months afterwards
1.3. Circulating cardiac biomarkers (amino-terminal pro-brain natriuretic peptide), assessed using blood samples at the baseline, 24 hours before the end of each treatment cycle, at the end of treatment and 3 months afterwards
2. Cardiac health outcomes will be assessed at the baseline, at the end of treatment and 3 months afterwards:
2.1. Resting blood pressure, measured in a seated comfortable position using a cardiac monitor
2.2. Resting heart rate, measured in a seated comfortable position using a cardiac monitor
2.3. Resting heart rate variability, measured in a seated comfortable position after at least 5 minutes of rest using a Polar V800 heart rate monitor with a Polar H7 Heart Rate Sensor chest strap. Analysis will be done using Kubios v2 Heart Rate Variability software.
2.4. Heart rate recovery (measured using a cardiac monitor after 30 seconds and 60 seconds after completion of a cardiopulmonary test), defined as the difference between peak heart rate achieved in the cardiopulmonary test and the heart rate at 30 seconds and 60 seconds following this.
Secondary outcome measures
All secondary outcomes will be measured at the baseline, at the end of treatment and 3 months afterwards:
1. Functional outcomes:
1.1. Cardiopulmonary capacity (maximum oxygen consumption), evaluated using a Bruce treadmill test with an echocardiogram and continuous analysis of the O₂/CO₂ exchange
1.2. Upper limb strength (maximum voluntary handgrip strength), assessed using a handgrip dynamometer (6 trials per participant with 3 in each arm)
1.3. Lower limb functionality, assessed using the sit-stand test
2. Health-related quality of life and fatigue, assessed using the European Organization for Research and Treatment in Cancer Quality of Life C-30 (EORTC QLQ-C30) questionnaire
3. Neuropathy-related chemotherapy, assessed using The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group -Neurotoxicity (FACT/GOG-Ntx) Scale)
Overall trial start date
Overall trial end date
Reason abandoned (if study stopped)
Participant inclusion criteria
2. Aged 18 years or older
3. Histological confirmation of invasive breast cancer
4. Breast cancer stage IA-IIIC
5. Scheduled to receive neoadjuvant or adjuvant anthracycline-containing chemotherapy and/or trastuzumab by the Multidisciplinary Group Consultation of Centro Hospitalar de Vila Nova de Gaia/Espinho decision
6. Able to provide informed consent
7. Acceptance of randomization to intervention group or control group
Target number of participants
Participant exclusion criteria
1. Heart failure class >1 of the New York Heart Association.
2. Osteoporosis (Tscore < 2.5)
3. Contraindications to maximal exercise testing
4. Usual medication containing beta-blockers
5. Severe anaemia (<8 g/dl) that cannot be corrected with transfusion and/or replacement of iron deficiency and/or vitamin deficiency
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Centro Hospitalar de Vila Nova de Gaia/Espinho
Rua Conceição Fernandes, s/n
Vila Nova de Gaia
Centro Hospitalar de Vila Nova de Gaia/ Espinho
Rua da Conceição Fernandes s/n
Vila Nova de Gaia
Universidade da Beira Interior
Convento de Sto. António
Direção Geral de Saúde
Alameda D. Afonso Henriques
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
The findings will be:
1. Involved in a doctoral thesis
2. Submitted to a peer-reviewed journal for publication.
3. Presented at conferences and the whole community concerned
IPD sharing statement:
The data that will support the findings of this study will be available on request from the corresponding author Pedro Antunes (firstname.lastname@example.org). The request will be analysed by the research team and the ethics committee that ethically approved the study.
Intention to publish date
Participant level data
Available on request
Basic results (scientific)