Effects of a Physical Exercise Program on Cardiovascular, Metabolic, Physical Fitness and Quality of Life in Cancer Survivors' Adult Women
Phase: NA
Conditions: Breast Cancer, Vascular Disease，Peripheral, Arterial Hypertension, Endothelial Dysfunction, Metabolic Disease
Sponsor: Cristian Alvarez

EFFECTS OF A PHYSICAL EXERCISE PROGRAM ON CARDIOVASCULAR, 
METABOLIC, PHYSICAL FITNESS AND QUALITY OF LIFE IN CANCER 
SURVIVORS’ ADULT WOMEN  
Date: December 27th, 2024 
 
 
 
 
 
 
 
 
Study documents 
 
 
 
 
 
 
 
 
 
 
 

SCIENTIFIC BACKGROUND: In Chile, in the year 2022, it was reported that the main 
causes of death are diseases of the circulatory system (31,606) and cancer (with 28,453 
deaths) (1). Both causes of death come from diseases such as arterial hypertension, 
diabetes, obesity, highly linked to sedentary lifestyles (i.e., spending long hours sitting), 
physical inactivity (i.e., not adhering to the international recommendations of physical 
activity per week of 150 to 300 min of low to moderate intensity physical activity, or 75 
to 150 min of vigorous physical activity per week) (2) and lifestyle (i.e., healthy eating, 
and inflammation processes such as cancer). Worryingly, in the Bío-Bío region alone, 
women's deaths from cancer reported 1,380 deaths, one of the highest in the country (3).  
Exercise training (i.e., defined as a particular type of physical activity guided by 
a professional and regulated overtime) has demonstrated evidence of the prevention and 
treatment of cancer (4), as well as in diabetes and arterial hypertension (co-morbidities). 
This has been raised by the American College of Sports Medicine (ACSM) (4), 
emphasizing the evidence in favor of the practice of exercise training (i.e., particularly 
aerobic and strength-type exercise) from the strongest (anxiety, depression, fatigue, 
quality of life, lymphedema, physical function) to the least amount of evidence (cardio-
vascular, pain, etc). 
Despite the “solid” evidence in favor of the effects of exercise training in cancer 
survivors (CS) to improve variables such as anxiety, depressive symptoms, fatigue, 
quality of life, lymphedema, and physical function, unfortunately they are still unknown 
and there is minimal evidence about the effects of exercise training on cardio-vascular 
and metabolic variables in cancer survivors’ persons (4). The phenomenon of the exercise 
training in CS persons is of relevance, because as it is pointed out, cancer is the second 
cause of death in Chile, and in particular breast cancer is the first cause among all types 
of cancer, and where the exercise training has a relevant value as a treatment and post-

treatment. Thus, it is required to fill the scientific gap in terms of the need to increase the 
evidence of exercise training in cardio-vascular physiology, such as parameters related to 
blood pressure (5), and endothelial dysfunction such as carotid intima-media thickness 
(cIMT), dilation-mediated flow (FMD) and pulse wave velocity (PWV) (6), as well as 
metabolic factors related to metabolism during exercise of oxidative and glycolytic type, 
which determine the oxidation of fat and glucose during exercise. There is consolidated 
or “solid” evidence (7), about the effects of physical exercise (i.e., exercise guided by a 
professional and planned over time), according to the American College of Sports 
Medicine (ACSM) exercise recommendations guide for CS (4).  
Different types of exercise training modalities have been reported in CS 
individuals during and following the completion of their treatment (Radiotherapy, 
Chemotherapy, Hormonal therapy), where the benefits of aerobic nature exercise training 
predominantly (i.e., exercises that promote an increase in aerobic enzymatic activity, 
mitochondrial biogenesis and in general oxidative metabolism [that promote the 
elaboration of ATP via fatty acids]) in combination with muscle strength as resistance 
training with the use of external overloads (i.e., controlled exercises with a certain level 
of muscle load based on prior assessment of maximal strength, usually measured by 
means of 1-repetition maximal test on different muscle groups), which are exercises that 
promote an increase in protein synthesis, muscle mass formation, and therefore both types 
of exercise training (Moderate-intensity continuous [MICT] + resistance training [RT]) 
are usually referred to in the literature as combined exercise or concurrent exercise 
(MICT+RT) (8). Among the main effects or benefits of exercise training in CS 
individuals, particularly in terms of reducing anxiety, depressive symptoms, fatigue, 
quality of life, lymphedema, and physical function (4). It has also been reported that there 
is only “moderate” evidence on the effects of exercise in CS at the level of bone health, 

and sleep, but worryingly, there is insufficient evidence in favor of physical exercise at 
the level of vascular function, falls, cognitive function, and pain, among other health 
parameters (sexual function, nausea, peripheral neuropathies). The potential results of the 
project will ultimately translate into greater technical, scientific and management 
knowledge to be able to analyze the increase in the offer of physical exercise programs 
or workshops for CS persons in Chile. The latter should translate into an improvement 
not only in the physical condition and health of CS people, but also in a lower risk of 
relapsing into cancer, mental illnesses (depression) and, of course, a reduction in 
mortality. From here, high-intensity interval training, a particular exercise modality of 
brief intense exercise intervals have been poorly studied in breast CS (9). Similarly, RT 
using lower exercise intensities (i.e., one repetition maximum test [1RM] load of ≤60% 
of 1 RM) have been also little tested for cardio-vascular (i.e., PWV, FMD, and cIMT) 
and metabolic health in breast CS women. Preliminary evidence show that concurrent 
exercise training decrease blood pressure, and that HIIT also decrease arterial stiffness in 
adult women. Sawyer et al. reported that 8-weeks of HIIT was superior to MICT for 
increasing FMD in HIIT vs MICT (Δ+8.9 vs. 5.1%) (10). Deisenroth et al. (11) showed 
that 12-week of HIIT (four sets [4 min] intervals at 80-90% HRmax with resting periods of 
60-70% HRmax cycling) reduced minimally PWV (−0.1 m·s-1) in hypertensive older adults 
(11). One-year of HIIT (60 s interval, 60 s of resting at 90% of the reserve oxygen 
consumption) decreased both systolic [SBP] (Δ−6.5)/diastolic [DBP] blood pressure 
(Δ−4.2 mmHg), and decreased cIMTav (Δ−0.95 mm) (12).  
Thus, concurrent training of both HIIT plus RT in lower 1RM intensities could 
promote potential benefits for both cardiovascular health and metabolic and physical 
condition parameters of breast CS women, however, there is scarcity of studies about this 

exercise modalities in patients who are CS and that have been exposure to higher and 
lower chemotherapy doses (13-15).  
RESEARCH PROBLEM: Despite the “solid” evidence in favor of the effects of 
exercise training in breast CS to improve variables such as anxiety, depressive symptoms, 
fatigue, quality of life, lymphedema and physical function, however, unfortunately, the 
effects of exercise training on cardio-vascular and metabolic variables, there is still 
unknown the effects of concurrent exercise training including HIIT plus RT in lower 1RM 
doses in CS women at level of their cardio-vascular and metabolic health.  
This is due to the fact that year after year there is an increase in the number of 
early diagnoses, as well as an increase in the number of CS with a successful completion 
of their breast cancer treatment (Radiotherapy, Chemotherapy, Hormonal Therapy), 
which also leads as an effect to an inherent increase in the number of CS persons, 
requiring the insertion of this population back into active life. Another effect of the 
scientific rationale lies in the scarce offer of physical activity and/or exercise training 
programs for this population of women between 40 and 70 years of age, which would be 
significantly overcome with the application of the present intervention project that would 
report cardiovascular, metabolic, physical condition, quality of life and eating patterns 
variables. OBJECTIVES; GENERAL: To determine the effects of traditional therapy 
added to physical exercise on cardio-vascular, metabolic and physical fitness in female 
breast cancer survivors who received lower (≤ 7 sessions) and higher (≥8 sessions) of 
chemotherapy.  
This study will follow the CONSORT guidelines for randomised trials, will be 
developed in accordance with the Declaration of Helsinki (2013), and has been approved 
by the BIOETICAL COMMITTEE OF UNIVERSIDAD ANDRES BELLO (Approval 
005/2024 of April 12th). Design: An experimental clinical randomized study. Methods: 

Adult women breast cancer survivors who have undergone all the stages related to breast 
cancer treatment (chemotherapy, radiotherapy, hormone therapy). The study will be 
carried out in the facilities of the Exercise Physiology Laboratory of the Exercise and 
Rehabilitation Sciences Institute of the Universidad Andrés Bello, Concepción city, from 
different community cancer survivors’ social groups of the Concepcion, Chile will be 
invited to participate of this study. The groups will be randomly allocated to an 
experimental group of high chemotherapy exposure (EG-HCHT, n=15) or to and 
experimental group of low chemotherapy exposure (EG-LCHT, n=15), that will adhere 
to 6-weeks of an exercise training program of concurrent training of HIIT plus RT three 
weekly.  
Inclusion criteria: a) breast cancer diagnosed, b) with or without chemotherapy 
treatment, c) normal weight body mass index [BMI] 18.6 to 24.9 or overweight/obesity 
condition by BMI 25.0 to 39.9 kg/m2, d) age 30 to 75 years, e) with or without other 
associated co-morbidities (diagnosed of elevated fasting glucose, prediabetes or diabetes, 
hypertension 
or 
prehypertension, 
or 
metabolic 
syndrome, 
fatty 
liver 
or 
hypercholesterolemia or screened by our research team), f) with or without hormonal 
therapy, and g) with or without other pharmacotherapy for specific muscle-groups such 
as morphine patches, morphine droplets or other pharmacological therapy for SOS pain 
treatment. Exclusion criteria: a) history of abnormal ECG, or diagnosis of other cardio-
vascular condition/history other than hypertension, vasculopathy, b) history of 
uncontrolled stage 3 of hypertension or hypertensive crisis, c) diabetes complications 
such as varicose ulcers, nephropathies, d) skeletal muscle abnormalities (e.g., knee, or hip 
arthrosis, muscle pain), e) using weight loss treatment/pharmacotherapy or being active 
in exercise training programs (or within the past three months), and f) use other 
pharmacotherapy that can influence body weight loss, g) respiratory disease type (chronic 

obstructive disease), h) kidney disease, i) pregnancy, and j) smoking behaviour or 
dependence on other substances. 
 
REFERENCES 
1. 
MINSAL. Tabla de resumen de mortalidad por causa, según sexo y región 2023 
[Available from: https://informesdeis.minsal.cl/SASVisualAnalytics/. 
2. 
WHO. WHO Guidelines on Physical Activity and Sedentary Behaviour. Geneva; 
2021. 
3. 
García Jofré N. Tendencia temporal de la tasa de mortalidad por cáncer de mama 
en mujeres en Chile, periodo 2007-2020. 2024. 
4. 
Campbell KL, Winters-Stone K, Wiskemann J, May AM, Schwartz AL, Courneya 
KS, et al. Exercise guidelines for cancer survivors: consensus statement from 
international multidisciplinary roundtable. Medicine and science in sports and exercise. 
2019;51(11):2375. 
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WHO. Global report on hypertension: The race against a silent killer. Geneva; 
2023.  Contract No.: CC By-NC-SA 3.0 IGO. 
6. 
Cameron AC, Touyz RM, Lang NN. Vascular complications of cancer 
chemotherapy. Canadian Journal of Cardiology. 2016;32(7):852-62. 
7. 
Wolin KY, Schwartz AL, Matthews CE, Courneya KS, Schmitz KH. 
Implementing the exercise guidelines for cancer survivors. The journal of supportive 
oncology. 2012;10(5):171. 
8. 
Vallerand JR, Rhodes RE, Walker GJ, Courneya KS. Correlates of meeting the 
combined and independent aerobic and strength exercise guidelines in hematologic 
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9. 
Gibala MJ, Little JP, MacDonald MJ, Hawley JA. Physiological adaptations to 
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physiology. 2012;590(5):1077-84. 
10. 
Sawyer BJ, Tucker WJ, Bhammar DM, Ryder JR, Sweazea KL, Gaesser GA. 
Effects of high-intensity interval training and moderate-intensity continuous training on 
endothelial function and cardiometabolic risk markers in obese adults. Journal of Applied 
Physiology. 2016;121(1):279-88. 
11. 
Deiseroth A, Streese L, Köchli S, Wüst RS, Infanger D, Schmidt-Trucksäss A, et 
al. Exercise and arterial stiffness in the elderly: a combined cross-sectional and 
randomized controlled trial (EXAMIN AGE). Frontiers in physiology. 2019;10:1119. 
12. 
Magalhães JP, Melo X, Correia IR, Ribeiro RT, Raposo J, Dores H, et al. Effects 
of combined training with different intensities on vascular health in patients with type 2 
diabetes: a 1-year randomized controlled trial. Cardiovascular diabetology. 2019;18(1):1-
13. 
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Beitzen-Heineke A, Rolling CC, Seidel C, Erley J, Molwitz I, Muellerleile K, et 
al. Long-term cardiotoxicity in germ cell cancer survivors after platinum-based 
chemotherapy: cardiac MR shows impaired systolic function and tissue alterations. 
European Radiology. 2024;34(6):4102-12. 
14. 
Austin D, Maier RH, Akhter N, Sayari M, Ogundimu E, Maddox JM, et al. 
Preventing cardiac damage in patients treated for breast cancer and lymphoma: the 
PROACT clinical trial. Cardio Oncology. 2024;6(5):684-96. 

15. 
Vo JB, Ramin C, Veiga LH, Brandt C, Curtis RE, Bodelon C, et al. Long-term 
cardiovascular disease risk after anthracycline and trastuzumab treatments in US breast 
cancer survivors. JNCI: Journal of the National Cancer Institute. 2024:djae107. 
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Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2013. 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

STATISTICAL ANALYSIS PLAN (SAP): Data will be presented as the mean ± 
standard deviation (SD). Normality and homoscedasticity assumptions will be tested by 
using Shapiro-Wilk tests and homoscedasticity by the Levene test. For those outcomes 
with normal distribution, paired t-test was applied to test differences, while to those with 
no normal distribution, unpaired t-test was applied. Cohen’s d effect size (<0.2 = 
negligible, 0.2-0.49 = small, 0.5-0.79 = moderate, ≥0.8 = large) for interactions that 
showed statistically significant (16). Each delta (∆), pre-post changes, of main and 
secondary outcomes will be calculated in all groups. To test the associations among main 
vascular outcomes (PWV, FMD, cIMTav, cIMTmax) with anthropometric, body 
composition, metabolic, cardio-vascular outcomes, and physical fitness outcomes, simple 
linear regression (to parametric) with R2 prediction percentage, or the Rho Spearman 
nonparametric correlation (rs = ) will be applied. Statistical analyses will be developed 
using Prism 8.0 software (Graph Pad, San Diego, CA, United States), and the SPSSTM 
software 29 version for Windows (IBM SPSS Inc., Chicago, IL, USA). The alpha level 
will be fixed at (P≤0.05) for all statistical significance.