Breast CancerNCT07823660
Cardio-Oncology Rehabilitation in Breast Cancer Patients Undergoing Chemotherapy
A study testing Cardio-Oncology Exercise Rehabilitation Program in people with Breast Cancer, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
Trial summary
Breast cancer is the most prevalent malignancy among women in Brazil, and Porto Alegre (Rio Grande do Sul) has one of the highest incidence rates in women under 50, with 165.5 cases per 100,000 women aged 40-49. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Cardio-Oncology Exercise Rehabilitation Program
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Dec 2025to Aug 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of breast cancer
- Indicated for chemotherapy treatment
- Cardiovascularly stable
- Cleared for physical exercise
- Willing to participate in the study
- Physically able to perform the assessments and training sessions
Who cannot join
- Any decompensated disease that would compromise the ability to perform the training sessions
- Prior diagnosis of ischemic heart disease
- Prior diagnosis of valvular heart disease
- Prior diagnosis of cardiac arrhythmias
- Myocarditis within the past 6 months
- History of heart failure
Show all 11Show fewer
- LVEF <55% prior to initiation of chemotherapy
- Musculoskeletal disorders that limit the ability to perform the exercises
- Diagnosis of peripheral arterial occlusive disease within the past 6 months
- Ankle-brachial index <0.4
- Cognitive impairment that would compromise understanding of study procedures or participation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90410000
Rosane M Nery, PhD, +55 51 33597634, rnery@hcpa.edu.br
About this study
Official title: Effect of Chemotherapy Treatment on the Cardiovascular System: Clinical Profile of Patients Diagnosed With Breast Cancer and an Integrated Cardio-Oncology Rehabilitation Approach. A Randomized Clinical Trial
Breast cancer is the most prevalent malignancy among women in Brazil, and Porto Alegre (Rio Grande do Sul) has one of the highest incidence rates in women under 50, with 165.5 cases per 100,000 women aged 40-49. Advances in cancer biology, treatment, and supportive care have improved outcomes, leading to increased survivorship. Regular physical exercise has been shown to be an effective strategy in both the prevention and management of breast cancer, and during chemotherapy, physical activity may reduce fatigue, improve quality of life, and increase cardiorespiratory fitness.
This randomized clinical trial will enroll women diagnosed with breast cancer indicated for neoadjuvant or adjuvant chemotherapy. The study aims to characterize the clinical profile of these patients with respect to cardiovascular and functional effects of chemotherapy, and to evaluate an integrated cardio-oncology rehabilitation approach.
The investigators expect to identify the clinical profile of breast cancer patients undergoing chemotherapy and establish associations with the study variables, as well as to assess the effect of a standardized exercise program on the cardiovascular and musculoskeletal systems and quality of life. Based on these results, the study aims to propose a complementary rehabilitation program, to be offered within the public health system, alongside pharmacological treatment during and after completion of the chemotherapy cycle.
Read the detailed description
Breast cancer (BC) is highly prevalent worldwide, and in Brazil, particularly in the state of Rio Grande do Sul (RS), it is the leading cause of morbidity and mortality from malignant neoplasms among women. Five-year survival rates exceed 80% in developed countries, whereas in Brazil there is considerable variation across regions and cities. Studies indicate that Porto Alegre, the capital of RS, has one of the highest incidence rates of breast cancer among women under 50 years of age, with 165.5 cases per 100,000 women aged 40 to 49 years.
Several risk factors are associated with the development of breast cancer, including family history of the disease, use of oral contraceptives, obesity, and alcohol consumption. Notably, obesity and alcohol consumption differentially increase the risk of specific molecular subtypes of breast cancer. In addition, physical inactivity and elevated body mass index (BMI) are significant risk factors for breast cancer in postmenopausal women.
Although chemotherapy is essential in oncologic treatment, it is associated with adverse effects on the cardiovascular system. Advances in pharmacologic therapy, together with a greater understanding of disease mechanisms, have led to increased survival and improved health-related well-being among cancer patients. However, this increased survival is accompanied by greater exposure to cardiovascular risk factors and clinically unfavorable outcomes, such as cardiotoxicity caused by chemotherapeutic agents.
Cardiotoxicity, classified as acute, subacute, or chronic, is generally assessed based on changes in left ventricular ejection fraction (LVEF). Nevertheless, there is no universally accepted conceptual definition of chemotherapy-induced cardiotoxicity; definitions vary according to study design, etiology, epidemiology, and prevention strategies.
Adjuvant chemotherapy is used in up to 27% of breast cancer cases. The mechanisms underlying cardiotoxicity and the progression of cardiac dysfunction over time may be explained by: (1) increased myocardial oxidative stress; (2) disruption of mitochondrial calcium homeostasis; (3) impairment of mitochondrial energy metabolism; (4) degradation of ultrastructural proteins; (5) direct DNA damage via inhibition of topoisomerase 2β; and (6) direct cytotoxic effects on cardiac progenitor cells, reducing the heart's reparative capacity following myocardial injury.
Clinical diagnosis of cardiotoxicity cannot be limited to a simple measurement of LVEF. Evidence highlights the importance of evaluating additional outcomes beyond structural changes and reduced LVEF, including cardiac arrhythmias, coronary artery disease, blood biomarkers, and vascular function.
Cardiotoxicity and Vascular Function Endothelial cells are characterized by heterogeneous structure and function, with phenotypic variation according to their location in different organs, tissues, or blood vessel types. Positioned at the interface between blood and tissue, the endothelium plays a key role in the cardiovascular system, including regulation of vascular tone, synthesis and secretion of signaling molecules, and control of hemostasis, coagulation, inflammatory response, and atherogenesis.
Chemotherapeutic agents are generally administered via the systemic circulation. As a result, endothelial cells are among the first to be affected by these drugs, even before cardiac tissue itself. Vascular endothelial health is progressively compromised, with endothelial cells becoming increasingly vulnerable to inflammatory stressors, generation of reactive oxygen species, and reduced nitric oxide bioavailability - factors that directly contribute to the development and progression of atherosclerotic disease.
In addition to inflammatory markers and adhesion molecules, endothelial function can be assessed using brachial artery flow-mediated dilation (FMD), a technique first developed in 1992. This non-invasive method measures brachial artery diameter before and after forearm ischemia induced by inflating a cuff on the distal portion of the arm; FMD is expressed as the percentage increase in brachial artery diameter following release of the ischemic stimulus (reactive hyperemia). This vasodilation is mediated by endothelial release of nitric oxide in response to arterial wall shear stress.
Nagy et al. evaluated 22 patients with a clinical diagnosis of lymphoma treated with doxorubicin (DOX), measuring FMD before and after (at 6, 12, 24, and 48 hours) chemotherapy administration. The study's main finding was a significant reduction in FMD values (9.9±4.4% vs. 6.1±4.6%, P<0.02). In the same line of research, other findings established significant associations between baseline FMD values and changes in LVEF at 3 months (r = 0.433; p = 0.044) and at 6 months (r = 0.581; p = 0.023) among patients who developed cardiotoxicity following anthracycline treatment. Based on these results, the authors suggest that FMD assessment may play an important role as a risk-stratification tool and an early marker of chemotherapy-induced cardiotoxicity.
Breast Cancer and Physical Exercise As noted above, several risk factors are associated with the development of breast cancer, including family history, use of oral contraceptives, obesity, and alcohol consumption, with obesity and alcohol consumption differentially increasing the risk of specific molecular BC subtypes. Physical inactivity and elevated BMI are also significant risk factors for breast cancer in postmenopausal women.
Regular physical exercise has been shown to be an effective strategy in both the prevention and management of breast cancer. During chemotherapy treatment, physical activity may reduce fatigue, improve quality of life, and increase cardiorespiratory fitness. Studies indicate that supervised exercise programs combining aerobic and resistance training are particularly effective in reducing fatigue among women undergoing adjuvant chemotherapy.
After completion of chemotherapy, continued engagement in physical exercise remains equally beneficial. Evidence suggests that regular physical activity is associated with lower all-cause and breast-cancer-specific mortality among survivors. In addition, exercise interventions have been shown to improve self-reported cognitive function, physical fitness, fatigue, and quality of life, and to reduce depressive symptoms in breast cancer patients exposed to chemotherapy.
Given this context, this project proposes to study the clinical profile of women diagnosed with breast cancer with respect to the effects of chemotherapy treatment and the implementation of a physical exercise program on the cardiovascular system and functional capacity, through an integrated cardio-oncology rehabilitation approach, in patients treated within the Brazilian Unified Health System (SUS), cared for at a university hospital or referred from the RS public health network.
Hypotheses Null Hypothesis (H0): In women diagnosed with breast cancer, chemotherapy treatment does not produce statistically significant changes in the following clinical and laboratory outcomes: vascular function (assessed by flow-mediated dilation or ankle-brachial index); cardiac function (assessed by echocardiography or other complementary tests); functional capacity (assessed by the six-minute walk test or VO2 consumption); and inflammatory, endothelial, and cardiovascular biomarkers.
Alternative Hypothesis (H1): In women diagnosed with breast cancer, chemotherapy treatment produces statistically significant changes in the following clinical and laboratory outcomes: reduced vascular function; impaired cardiac function; decreased functional capacity; and altered levels of inflammatory, endothelial, and cardiovascular biomarkers.
- Conditions
- Breast Cancer
- Being tested
- Cardio-Oncology Exercise Rehabilitation Program
- Keywords
- Breast cancer, Chemotherapy, Cardio-oncology rehabilitation
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardio-Oncology Exercise Rehabilitation ProgramBehavioural
Structured, individualized exercise training sessions held twice weekly at HCPA's Physical Rehabilitation Service (SFR), aimed at mitigating chemotherapy-related cardiovascular and functional impairment in breast cancer patients.
| Study group | Role | What they receive |
|---|---|---|
| Exercise Training Group | Experimental | Participants will undergo a cardio-oncology rehabilitation program with supervised exercise training sessions twice weekly at HCPA's Physical Rehabilitation Service (SFR). Assessments will be performed at baseline and at 3 and 6 months. Receives: Behavioral: Cardio-Oncology Exercise Rehabilitation Program |
| Control Group | No intervention | Participants will receive general health and nutritional guidance at the baseline assessment and will maintain usual care, without a structured exercise program. Assessments will be performed at baseline and at 3 and 6 months, following the same schedule as the intervention group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Left Ventricular Ejection Fraction (LVEF)
Left ventricular systolic function assessed by transthoracic echocardiography with strain analysis
Measured: Baseline and 6 months
Incidence of Cardiotoxicity
Development of cancer therapy-related cardiac dysfunction, including asymptomatic/subclinical cases, defined by relative decline in global longitudinal strain (GLS) on echocardiography.
Measured: Baseline and 6 months
Change in Electrocardiographic Abnormalities and Arrhythmias
ECG findings assessed as part of the echocardiographic evaluation. The ECG will be assessed for the following parameters: heart rate, cardiac rhythm (to identify arrhythmias), PR interval, QRS complex duration and morphology, QT/QTc interval, and ST-segment/T-wave changes.
Measured: Baseline and 6 months
Change in Resting Blood Pressure
Measured before cardiopulmonary exercise testing (CPET)
Measured: Baseline and 6 months
Change in Blood Pressure During Exercise
Measured during cardiopulmonary exercise testing (CPET)
Measured: Baseline and 6 months
Change in Resting Heart Rate
Measured before cardiopulmonary exercise testing (CPET)
Measured: Baseline and 6 months
Change in Heart Rate During Exercise
Measured during cardiopulmonary exercise testing (CPET)
Measured: Baseline and 6 months
Change in Peak Oxygen Consumption (VO2 Peak)
Measured during cardiopulmonary exercise testing (CPET)
Measured: Baseline and 6 months
Fatigue Pictogram (Mota, Pimenta, Fitch, 2009)
This pictorial instrument assesses fatigue intensity and fatigue interference with usual activities, each rated on a scale from 1 to 5, where higher scores indicate worse outcomes (greater fatigue intensity and greater interference with activities, respectively).
Measured: Baseline, 3 months, and 6 months
Modified Borg CR-10 Scale (Category-Ratio 10)
This scale ranges from 0 (no exertion/dyspnea at all) to 10 (maximal/very, very severe exertion or dyspnea), where higher scores indicate worse perceived exertion or breathlessness.
Measured: Baseline, 3 months, and 6 months
Secondary outcomes (12)
Change in Troponin
Blood biomarker (troponin)
Measured: Baseline and 6 months
Change in BNP/NT-proBNP
Blood biomarker (BNP/NT-proBNP)
Measured: Baseline and 6 months
Change in High-Sensitivity C-Reactive Protein (hs-CRP)
Blood biomarker (hs-CRP)
Measured: Baseline and 6 months
Change in TNF-alpha
TNF-alpha
Measured: Baseline and 6 months
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Breast Cancer Module (EORTC QLQ-BR23)
This is a supplementary, disease-specific module used alongside the EORTC QLQ-C30. All scales and single-item measures are scored from 0 to 100 after linear transformation, following the EORTC QLQ-C30 Scoring Manual scoring algorithm. For the functional scales (Body Image, Sexual Functioning, Sexual Enjoyment, Future Perspective), higher scores indicate better functioning (better outcome). For the symptom scales/items (Systemic Therapy Side Effects, Breast Symptoms, Arm Symptoms, Upset by Hair Loss), higher scores indicate greater symptom burden (worse outcome)."
Measured: Baseline and 6 months
Change in Lean Body Mass
Bioelectrical impedance analysis
Measured: Baseline and 6 months
Change in Body Fat
Bioelectrical impedance analysis
Measured: Baseline and 6 months
Change in Muscle Mass Index
Bioelectrical impedance analysis
Measured: Baseline and 6 months
Change in Hand Grip Strength
Bilateral hand grip strength assessed by dynamometry
Measured: Baseline and 6 months
Rehabilitation Program Adherence
Percentage of prescribed exercise sessions attended
Measured: Throughout the 6-month study period
Reduction in Cardiovascular Adverse Events During Treatment
Number of adverse events during treatment
Measured: Throughout the 6-month study period
Change in Ankle-Brachial Index (ABI)
Doppler ultrasound ankle-brachial index
Measured: Baseline, 3 months, and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2026
- Study start1 Dec 2025
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rosane M Nery, PhD, Principal investigator, Hospital de Clinicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07823660
- Sponsor's protocol ID
- Dipe - 20250191
- Other IDs
- 97992026.9.0000.5327
- Status last verified
- Jul 2026
- First submitted
- 29 Jul 2026
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The study protocol establishes that participant data confidentiality and privacy will be maintained in accordance with Brazilian data protection regulations (LGPD, Law No. 13,709/2018) and national research ethics resolutions (CNS 466/2012, CNS 510/2016), with no provision in the approved protocol or informed consent form for sharing individual participant data with external researchers.
Publications
Renaud P, Blondin JP. The stress of Stroop performance: physiological and emotional responses to color-word interference, task pacing, and pacing speed. Int J Psychophysiol. 1997 Sep;27(2):87-97. doi: 10.1016/s0167-8760(97)00049-4.
PubMed 9342640MacLeod CM. Half a century of research on the Stroop effect: an integrative review. Psychol Bull. 1991 Mar;109(2):163-203. doi: 10.1037/0033-2909.109.2.163. No abstract available.
PubMed 2034749Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction; Thygesen K, Alpert JS, White HD, Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA, Chaitman BA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S; ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct;33(20):2551-67. doi: 10.1093/eurheartj/ehs184. Epub 2012 Aug 24. No abstract available.
PubMed 22922414Hudak PL, Amadio PC, Bombardier C. Development of an upper extremity outcome measure: the DASH (disabilities of the arm, shoulder and hand) [corrected]. The Upper Extremity Collaborative Group (UECG). Am J Ind Med. 1996 Jun;29(6):602-8. doi: 10.1002/(SICI)1097-0274(199606)29:63.0.CO;2-L.
PubMed 8773720Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, McLeod L, Delacqua G, Delacqua F, Kirby J, Duda SN; REDCap Consortium. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019 Jul;95:103208. doi: 10.1016/j.jbi.2019.103208. Epub 2019 May 9.
PubMed 31078660Do J, Cho Y, Jeon J. Effects of a 4-week multimodal rehabilitation program on quality of life, cardiopulmonary function, and fatigue in breast cancer patients. J Breast Cancer. 2015 Mar;18(1):87-96. doi: 10.4048/jbc.2015.18.1.87. Epub 2015 Mar 27.
PubMed 25834616Koevoets EW, Schagen SB, de Ruiter MB, Geerlings MI, Witlox L, van der Wall E, Stuiver MM, Sonke GS, Velthuis MJ, Jobsen JJ, Menke-Pluijmers MBE, Goker E, van der Pol CC, Bos MEMM, Tick LW, van Holsteijn NA, van der Palen J, May AM, Monninkhof EM; PAM study group. Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study). Breast Cancer Res. 2022 May 26;24(1):36. doi: 10.1186/s13058-022-01530-2.
PubMed 35619188Spei ME, Samoli E, Bravi F, La Vecchia C, Bamia C, Benetou V. Physical activity in breast cancer survivors: A systematic review and meta-analysis on overall and breast cancer survival. Breast. 2019 Apr;44:144-152. doi: 10.1016/j.breast.2019.02.001. Epub 2019 Feb 12.
PubMed 30780085Medeiros Torres D, Jorge Koifman R, da Silva Santos S. Impact on fatigue of different types of physical exercise during adjuvant chemotherapy and radiotherapy in breast cancer: systematic review and meta-analysis. Support Care Cancer. 2022 Jun;30(6):4651-4662. doi: 10.1007/s00520-022-06809-w. Epub 2022 Jan 22.
PubMed 35064331Joaquim A, Leao I, Antunes P, Capela A, Viamonte S, Alves AJ, Helguero LA, Macedo A. Impact of physical exercise programs in breast cancer survivors on health-related quality of life, physical fitness, and body composition: Evidence from systematic reviews and meta-analyses. Front Oncol. 2022 Dec 9;12:955505. doi: 10.3389/fonc.2022.955505. eCollection 2022.
PubMed 36568235Nagy L, Szabo F, Ivanyi J, Nemeth L, Kovacs GL, Palatka J, Tarjan J, Toth K, Roth E. A method for detection of doxorubicin-induced cardiotoxicity: Flow-mediated vasodilation of the brachial artery. Exp Clin Cardiol. 2001 Summer;6(2):87-92.
PubMed 20428269Thijssen DHJ, Bruno RM, van Mil ACCM, Holder SM, Faita F, Greyling A, Zock PL, Taddei S, Deanfield JE, Luscher T, Green DJ, Ghiadoni L. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J. 2019 Aug 7;40(30):2534-2547. doi: 10.1093/eurheartj/ehz350.
PubMed 31211361Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992 Nov 7;340(8828):1111-5. doi: 10.1016/0140-6736(92)93147-f.
PubMed 1359209Luu AZ, Chowdhury B, Al-Omran M, Teoh H, Hess DA, Verma S. Role of Endothelium in Doxorubicin-Induced Cardiomyopathy. JACC Basic Transl Sci. 2018 Dec 31;3(6):861-870. doi: 10.1016/j.jacbts.2018.06.005. eCollection 2018 Dec.
PubMed 30623145Mitry MA, Edwards JG. Doxorubicin induced heart failure: Phenotype and molecular mechanisms. Int J Cardiol Heart Vasc. 2016 Mar;10:17-24. doi: 10.1016/j.ijcha.2015.11.004.
PubMed 27213178
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Chemotherapy Treatment on the Cardiovascular System: Clinical Profile of Patients Diagnosed With Breast Cancer and an Integrated Cardio-Oncology Rehabilitation Approach. A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07823660
- Acronym / sponsor ID
- Dipe - 20250191
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, Chemotherapy, Cardio-oncology rehabilitation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Study start
- 1 Dec 2025 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 16 Sep 2026 (actual)
- 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.
Breast cancer is the most prevalent malignancy among women in Brazil, and Porto Alegre (Rio Grande do Sul) has one of the highest incidence rates in women under 50, with 165.5 cases per 100,000 women aged 40-49. Advances in cancer biology, treatment, and supportive care have improved outcomes, leading to increased survivorship. Regular physical exercise has been shown to be an effective strategy in both the prevention and management of breast cancer, and during chemotherapy, physical activity may reduce fatigue, improve quality of life, and increase cardiorespiratory fitness.
This randomized clinical trial will enroll women diagnosed with breast cancer indicated for neoadjuvant or adjuvant chemotherapy. The study aims to characterize the clinical profile of these patients with respect to cardiovascular and functional effects of chemotherapy, and to evaluate an integrated cardio-oncology rehabilitation approach.
The investigators expect to identify the clinical profile of breast cancer patients undergoing chemotherapy and establish associations with the study variables, as well as to assess the effect of a standardized exercise program on the cardiovascular and musculoskeletal systems and quality of life. Based on these results, the study aims to propose a complementary rehabilitation program, to be offered within the public health system, alongside pharmacological treatment during and after completion of the chemotherapy cycle.
Detailed description
Breast cancer (BC) is highly prevalent worldwide, and in Brazil, particularly in the state of Rio Grande do Sul (RS), it is the leading cause of morbidity and mortality from malignant neoplasms among women. Five-year survival rates exceed 80% in developed countries, whereas in Brazil there is considerable variation across regions and cities. Studies indicate that Porto Alegre, the capital of RS, has one of the highest incidence rates of breast cancer among women under 50 years of age, with 165.5 cases per 100,000 women aged 40 to 49 years.
Several risk factors are associated with the development of breast cancer, including family history of the disease, use of oral contraceptives, obesity, and alcohol consumption. Notably, obesity and alcohol consumption differentially increase the risk of specific molecular subtypes of breast cancer. In addition, physical inactivity and elevated body mass index (BMI) are significant risk factors for breast cancer in postmenopausal women.
Although chemotherapy is essential in oncologic treatment, it is associated with adverse effects on the cardiovascular system. Advances in pharmacologic therapy, together with a greater understanding of disease mechanisms, have led to increased survival and improved health-related well-being among cancer patients. However, this increased survival is accompanied by greater exposure to cardiovascular risk factors and clinically unfavorable outcomes, such as cardiotoxicity caused by chemotherapeutic agents.
Cardiotoxicity, classified as acute, subacute, or chronic, is generally assessed based on changes in left ventricular ejection fraction (LVEF). Nevertheless, there is no universally accepted conceptual definition of chemotherapy-induced cardiotoxicity; definitions vary according to study design, etiology, epidemiology, and prevention strategies.
Adjuvant chemotherapy is used in up to 27% of breast cancer cases. The mechanisms underlying cardiotoxicity and the progression of cardiac dysfunction over time may be explained by: (1) increased myocardial oxidative stress; (2) disruption of mitochondrial calcium homeostasis; (3) impairment of mitochondrial energy metabolism; (4) degradation of ultrastructural proteins; (5) direct DNA damage via inhibition of topoisomerase 2β; and (6) direct cytotoxic effects on cardiac progenitor cells, reducing the heart's reparative capacity following myocardial injury.
Clinical diagnosis of cardiotoxicity cannot be limited to a simple measurement of LVEF. Evidence highlights the importance of evaluating additional outcomes beyond structural changes and reduced LVEF, including cardiac arrhythmias, coronary artery disease, blood biomarkers, and vascular function.
Cardiotoxicity and Vascular Function Endothelial cells are characterized by heterogeneous structure and function, with phenotypic variation according to their location in different organs, tissues, or blood vessel types. Positioned at the interface between blood and tissue, the endothelium plays a key role in the cardiovascular system, including regulation of vascular tone, synthesis and secretion of signaling molecules, and control of hemostasis, coagulation, inflammatory response, and atherogenesis.
Chemotherapeutic agents are generally administered via the systemic circulation. As a result, endothelial cells are among the first to be affected by these drugs, even before cardiac tissue itself. Vascular endothelial health is progressively compromised, with endothelial cells becoming increasingly vulnerable to inflammatory stressors, generation of reactive oxygen species, and reduced nitric oxide bioavailability - factors that directly contribute to the development and progression of atherosclerotic disease.
In addition to inflammatory markers and adhesion molecules, endothelial function can be assessed using brachial artery flow-mediated dilation (FMD), a technique first developed in 1992. This non-invasive method measures brachial artery diameter before and after forearm ischemia induced by inflating a cuff on the distal portion of the arm; FMD is expressed as the percentage increase in brachial artery diameter following release of the ischemic stimulus (reactive hyperemia). This vasodilation is mediated by endothelial release of nitric oxide in response to arterial wall shear stress.
Nagy et al. evaluated 22 patients with a clinical diagnosis of lymphoma treated with doxorubicin (DOX), measuring FMD before and after (at 6, 12, 24, and 48 hours) chemotherapy administration. The study's main finding was a significant reduction in FMD values (9.9±4.4% vs. 6.1±4.6%, P<0.02). In the same line of research, other findings established significant associations between baseline FMD values and changes in LVEF at 3 months (r = 0.433; p = 0.044) and at 6 months (r = 0.581; p = 0.023) among patients who developed cardiotoxicity following anthracycline treatment. Based on these results, the authors suggest that FMD assessment may play an important role as a risk-stratification tool and an early marker of chemotherapy-induced cardiotoxicity.
Breast Cancer and Physical Exercise As noted above, several risk factors are associated with the development of breast cancer, including family history, use of oral contraceptives, obesity, and alcohol consumption, with obesity and alcohol consumption differentially increasing the risk of specific molecular BC subtypes. Physical inactivity and elevated BMI are also significant risk factors for breast cancer in postmenopausal women.
Regular physical exercise has been shown to be an effective strategy in both the prevention and management of breast cancer. During chemotherapy treatment, physical activity may reduce fatigue, improve quality of life, and increase cardiorespiratory fitness. Studies indicate that supervised exercise programs combining aerobic and resistance training are particularly effective in reducing fatigue among women undergoing adjuvant chemotherapy.
After completion of chemotherapy, continued engagement in physical exercise remains equally beneficial. Evidence suggests that regular physical activity is associated with lower all-cause and breast-cancer-specific mortality among survivors. In addition, exercise interventions have been shown to improve self-reported cognitive function, physical fitness, fatigue, and quality of life, and to reduce depressive symptoms in breast cancer patients exposed to chemotherapy.
Given this context, this project proposes to study the clinical profile of women diagnosed with breast cancer with respect to the effects of chemotherapy treatment and the implementation of a physical exercise program on the cardiovascular system and functional capacity, through an integrated cardio-oncology rehabilitation approach, in patients treated within the Brazilian Unified Health System (SUS), cared for at a university hospital or referred from the RS public health network.
Hypotheses Null Hypothesis (H0): In women diagnosed with breast cancer, chemotherapy treatment does not produce statistically significant changes in the following clinical and laboratory outcomes: vascular function (assessed by flow-mediated dilation or ankle-brachial index); cardiac function (assessed by echocardiography or other complementary tests); functional capacity (assessed by the six-minute walk test or VO2 consumption); and inflammatory, endothelial, and cardiovascular biomarkers.
Alternative Hypothesis (H1): In women diagnosed with breast cancer, chemotherapy treatment produces statistically significant changes in the following clinical and laboratory outcomes: reduced vascular function; impaired cardiac function; decreased functional capacity; and altered levels of inflammatory, endothelial, and cardiovascular biomarkers.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exercise Training Group | Experimental | Behavioral: Cardio-Oncology Exercise Rehabilitation ProgramParticipants will undergo a cardio-oncology rehabilitation program with supervised exercise training sessions twice weekly at HCPA's Physical Rehabilitation Service (SFR). Assessments will be performed at baseline and at 3 and 6 months. |
| Control Group | No intervention | –Participants will receive general health and nutritional guidance at the baseline assessment and will maintain usual care, without a structured exercise program. Assessments will be performed at baseline and at 3 and 6 months, following the same schedule as the intervention group. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of breast cancer
- Indicated for chemotherapy treatment
- Cardiovascularly stable
- Cleared for physical exercise
- Willing to participate in the study
Key exclusion criteria (11 listed)
- Any decompensated disease that would compromise the ability to perform the training sessions
- Prior diagnosis of ischemic heart disease
- Prior diagnosis of valvular heart disease
- Prior diagnosis of cardiac arrhythmias
- Myocarditis within the past 6 months
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 |
|---|---|---|
| Cardio-Oncology Exercise Rehabilitation ProgramStructured, individualized exercise training sessions held twice weekly at HCPA's Physical Rehabilitation Service (SFR), aimed at mitigating chemotherapy-related cardiovascular and functional impairment in breast cancer patients. | Behavioural | Exercise Training Group |
Primary outcome
Change in Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline and 6 months
Left ventricular systolic function assessed by transthoracic echocardiography with strain analysis
Incidence of Cardiotoxicity
Time frame: Baseline and 6 months
Development of cancer therapy-related cardiac dysfunction, including asymptomatic/subclinical cases, defined by relative decline in global longitudinal strain (GLS) on echocardiography.
Change in Electrocardiographic Abnormalities and Arrhythmias
Time frame: Baseline and 6 months
ECG findings assessed as part of the echocardiographic evaluation. The ECG will be assessed for the following parameters: heart rate, cardiac rhythm (to identify arrhythmias), PR interval, QRS complex duration and morphology, QT/QTc interval, and ST-segment/T-wave changes.
Change in Resting Blood Pressure
Time frame: Baseline and 6 months
Measured before cardiopulmonary exercise testing (CPET)
Change in Blood Pressure During Exercise
Time frame: Baseline and 6 months
Measured during cardiopulmonary exercise testing (CPET)
Change in Resting Heart Rate
Time frame: Baseline and 6 months
Measured before cardiopulmonary exercise testing (CPET)
Change in Heart Rate During Exercise
Time frame: Baseline and 6 months
Measured during cardiopulmonary exercise testing (CPET)
Change in Peak Oxygen Consumption (VO2 Peak)
Time frame: Baseline and 6 months
Measured during cardiopulmonary exercise testing (CPET)
Fatigue Pictogram (Mota, Pimenta, Fitch, 2009)
Time frame: Baseline, 3 months, and 6 months
This pictorial instrument assesses fatigue intensity and fatigue interference with usual activities, each rated on a scale from 1 to 5, where higher scores indicate worse outcomes (greater fatigue intensity and greater interference with activities, respectively).
Modified Borg CR-10 Scale (Category-Ratio 10)
Time frame: Baseline, 3 months, and 6 months
This scale ranges from 0 (no exertion/dyspnea at all) to 10 (maximal/very, very severe exertion or dyspnea), where higher scores indicate worse perceived exertion or breathlessness.
12 secondary outcomes
Change in Troponin
Time frame: Baseline and 6 months
Change in BNP/NT-proBNP
Time frame: Baseline and 6 months
Change in High-Sensitivity C-Reactive Protein (hs-CRP)
Time frame: Baseline and 6 months
Change in TNF-alpha
Time frame: Baseline and 6 months
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Breast Cancer Module (EORTC QLQ-BR23)
Time frame: Baseline and 6 months
Change in Lean Body Mass
Time frame: Baseline and 6 months
Change in Body Fat
Time frame: Baseline and 6 months
Change in Muscle Mass Index
Time frame: Baseline and 6 months
Change in Hand Grip Strength
Time frame: Baseline and 6 months
Rehabilitation Program Adherence
Time frame: Throughout the 6-month study period
Reduction in Cardiovascular Adverse Events During Treatment
Time frame: Throughout the 6-month study period
Change in Ankle-Brachial Index (ABI)
Time frame: Baseline, 3 months, and 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
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- Background: PubMed 2034749MacLeod CM. Half a century of research on the Stroop effect: an integrative review. Psychol Bull. 1991 Mar;109(2):163-203. doi: 10.1037/0033-2909.109.2.163. No abstract available.
- Background: PubMed 22922414Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction; Thygesen K, Alpert JS, White HD, Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA, Chaitman BA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S; ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct;33(20):2551-67. doi: 10.1093/eurheartj/ehs184. Epub 2012 Aug 24. No abstract available.
- Background: PubMed 8773720Hudak PL, Amadio PC, Bombardier C. Development of an upper extremity outcome measure: the DASH (disabilities of the arm, shoulder and hand) [corrected]. The Upper Extremity Collaborative Group (UECG). Am J Ind Med. 1996 Jun;29(6):602-8. doi: 10.1002/(SICI)1097-0274(199606)29:63.0.CO;2-L.
- Background: PubMed 31078660Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, McLeod L, Delacqua G, Delacqua F, Kirby J, Duda SN; REDCap Consortium. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019 Jul;95:103208. doi: 10.1016/j.jbi.2019.103208. Epub 2019 May 9.
- Background: PubMed 25834616Do J, Cho Y, Jeon J. Effects of a 4-week multimodal rehabilitation program on quality of life, cardiopulmonary function, and fatigue in breast cancer patients. J Breast Cancer. 2015 Mar;18(1):87-96. doi: 10.4048/jbc.2015.18.1.87. Epub 2015 Mar 27.
- Background: PubMed 35619188Koevoets EW, Schagen SB, de Ruiter MB, Geerlings MI, Witlox L, van der Wall E, Stuiver MM, Sonke GS, Velthuis MJ, Jobsen JJ, Menke-Pluijmers MBE, Goker E, van der Pol CC, Bos MEMM, Tick LW, van Holsteijn NA, van der Palen J, May AM, Monninkhof EM; PAM study group. Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study). Breast Cancer Res. 2022 May 26;24(1):36. doi: 10.1186/s13058-022-01530-2.
- Background: PubMed 30780085Spei ME, Samoli E, Bravi F, La Vecchia C, Bamia C, Benetou V. Physical activity in breast cancer survivors: A systematic review and meta-analysis on overall and breast cancer survival. Breast. 2019 Apr;44:144-152. doi: 10.1016/j.breast.2019.02.001. Epub 2019 Feb 12.
- Background: PubMed 35064331Medeiros Torres D, Jorge Koifman R, da Silva Santos S. Impact on fatigue of different types of physical exercise during adjuvant chemotherapy and radiotherapy in breast cancer: systematic review and meta-analysis. Support Care Cancer. 2022 Jun;30(6):4651-4662. doi: 10.1007/s00520-022-06809-w. Epub 2022 Jan 22.
- Background: PubMed 36568235Joaquim A, Leao I, Antunes P, Capela A, Viamonte S, Alves AJ, Helguero LA, Macedo A. Impact of physical exercise programs in breast cancer survivors on health-related quality of life, physical fitness, and body composition: Evidence from systematic reviews and meta-analyses. Front Oncol. 2022 Dec 9;12:955505. doi: 10.3389/fonc.2022.955505. eCollection 2022.
- Background: PubMed 20428269Nagy L, Szabo F, Ivanyi J, Nemeth L, Kovacs GL, Palatka J, Tarjan J, Toth K, Roth E. A method for detection of doxorubicin-induced cardiotoxicity: Flow-mediated vasodilation of the brachial artery. Exp Clin Cardiol. 2001 Summer;6(2):87-92.
- Background: PubMed 31211361Thijssen DHJ, Bruno RM, van Mil ACCM, Holder SM, Faita F, Greyling A, Zock PL, Taddei S, Deanfield JE, Luscher T, Green DJ, Ghiadoni L. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J. 2019 Aug 7;40(30):2534-2547. doi: 10.1093/eurheartj/ehz350.
- Individual participant dataSharing planned: No. The study protocol establishes that participant data confidentiality and privacy will be maintained in accordance with Brazilian data protection regulations (LGPD, Law No. 13,709/2018) and national research ethics resolutions (CNS 466/2012, CNS 510/2016), with no provision in the approved protocol or informed consent form for sharing individual participant data with external researchers.
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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.
Rosane M Nery, PhD principal investigator
Hospital de Clinicas de Porto Alegre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cardio-Oncology Exercise Rehabilitation Program in people with Breast Cancer, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
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 6 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rosane M Nery, PhD (+55 51 33597634, rnery@hcpa.edu.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Left Ventricular Ejection Fraction (LVEF) (time frame: Baseline and 6 months). The study lists 10 primary outcomes in all. 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 NCT07823660, which also lists 23 linked publications.
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 16 Sep 2026.