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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in Left Ventricular Ejection Fraction (LVEF)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Exercise Training Group
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.
干预措施: Cardio-Oncology Exercise Rehabilitation Program (Behavioral)
Control Group
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.
结局指标
主要结局
Change in Left Ventricular Ejection Fraction (LVEF)
时间窗: Baseline and 6 months
Left ventricular systolic function assessed by transthoracic echocardiography with strain analysis
Incidence of Cardiotoxicity
时间窗: 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
时间窗: 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
时间窗: Baseline and 6 months
Measured before cardiopulmonary exercise testing (CPET)
Change in Blood Pressure During Exercise
时间窗: Baseline and 6 months
Measured during cardiopulmonary exercise testing (CPET)
Change in Resting Heart Rate
时间窗: Baseline and 6 months
Measured before cardiopulmonary exercise testing (CPET)
Change in Heart Rate During Exercise
时间窗: Baseline and 6 months
Measured during cardiopulmonary exercise testing (CPET)
Change in Peak Oxygen Consumption (VO2 Peak)
时间窗: Baseline and 6 months
Measured during cardiopulmonary exercise testing (CPET)
Fatigue Pictogram (Mota, Pimenta, Fitch, 2009)
时间窗: 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)
时间窗: 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.
次要结局
- Change in Troponin(Baseline and 6 months)
- Change in BNP/NT-proBNP(Baseline and 6 months)
- Change in High-Sensitivity C-Reactive Protein (hs-CRP)(Baseline and 6 months)
- Change in TNF-alpha(Baseline and 6 months)
- European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Breast Cancer Module (EORTC QLQ-BR23)(Baseline and 6 months)
- Change in Lean Body Mass(Baseline and 6 months)
- Change in Body Fat(Baseline and 6 months)
- Change in Muscle Mass Index(Baseline and 6 months)
- Change in Hand Grip Strength(Baseline and 6 months)
- Rehabilitation Program Adherence(Throughout the 6-month study period)
- Reduction in Cardiovascular Adverse Events During Treatment(Throughout the 6-month study period)
- Change in Ankle-Brachial Index (ABI)(Baseline, 3 months, and 6 months)