Effects of a Short-Term Supervised Exercise Program in Women with Breast Cancer

Abstract

Background: Due to their high toxicity, cancer treatments produce multiple sequelae, including fatigue, which has a great impact on quality of life. Therefore, the aim of this study is to evaluate the efficacy on quality of life, fatigue, and functional capacity of a short-term exercise program combining aerobic exercise, resistance training, and stretching for 6 weeks in cancer patients. Methods: The design of the study was quasi-experimental, which included a group of 30 women who were receiving or had received in the last year chemotherapy, radiotherapy, or hormonal treatment. The exercise supervised program with vigorous intensity lasted for six weeks and consisted of three distinct blocks: aerobic exercise (25 min), resistance training (20 min), and stretching exercises (15 min). Before and after starting the exercise program quality of life (EORTC QLQ-C30 questionnaire), functional capacity [6 min Walking Test (6MWT), Handgrip Test (HGT), 30-Second Sit-to-Stand Test (30s-STST)], and fatigue (FACIT-F questionnaire) were measured. Results: In the EORTC QLQ-C30 questionnaire significantly higher scores were observed in the global health status scale (p < 0.05), as well as in the functional scale in the role functioning, emotional functioning, and cognitive functioning items (p < 0.05), indicating a higher quality of life and overall health level. There was also a reduction in fatigue (p < 0.05), obtaining higher scores on the FACIT-F questionnaire after the exercise program. Additionally significant improvements are observed in 6MWT, HGT, and 30s-STST following the implementation of the exercise program (p < 0.05). Conclusions: A 6-week exercise protocol, with a vigorous intensity, including resistance training, endurance, and stretching exercises can produce significant improvements in quality of life and reduction in fatigue, as well as improve muscle strength and functional capacity.

1. Introduction

Cancer represents a significant public health issue globally [1], being the leading cause of death worldwide, accounting for nearly 10 million deaths in 2020 (about one-sixth of all deaths recorded) [2]. In 2018, the International Agency for Research on Cancer (IARC) estimated that there were 18.1 million new cases of cancer and 9.6 million deaths worldwide, reporting a 20% chance of developing it before the age of 75, and a mortality rate of 10% [3]. Two years later, in 2020, the IARC estimated that there were 19.3 million new cancer cases and nearly 10 million cancer deaths worldwide [2]. The most commonly diagnosed cancers worldwide were female breast cancer with 2.3 million new cases (11.7%), followed by lung cancer (11.4%), colorectal cancer (10.0%), prostate cancer (7.3%), and stomach cancer (5.6%), with the most common causes of death being lung cancer with 1.8 million deaths (18%), followed by colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and breast cancer in women (6.9%) [4]. In the United States, it is estimated that there were approximately 2 million new cancer cases and over 600,000 cancer-related deaths in 2023, with a 40% probability of developing cancer at some point in life (12.9% female breast, 12.6% male prostate, 4.3% male colorectal, and 3.9% female colorectal) [5]. The World Cancer Research Fund estimated in 2018 that 18% of cancers in the United States (more than 300,000 cases of cancer each year) are directly attributable to suboptimal diet, physical inactivity, and/or excess adiposity [6].

Treatments for this disease are varied, with the most common being surgery, chemotherapy, radiation therapy, and immunotherapy [7,8,9]. Some of these treatments, due to their toxicity, result in multiple health-detrimental consequences that occur in addition to those caused by the disease itself. Some of these sequelae include lymphedema, central and peripheral nervous system impairments, cardiac alterations, decreased bone and muscle mass, among others [10].

One of the most prevalent and troublesome symptoms experienced by patients is fatigue [11], characterized by a distressing, enduring, and subjective sense of exhaustion or tiredness, affecting both emotional and cognitive aspects, and often disproportionate to their level of activity, significantly interfering with their usual functioning [12]. Fatigue may increase before the start of treatment and typically increases during cancer treatment, including radiation therapy [13], chemotherapy [14], hormonal, and/or biological therapies [15]. This fatigue is associated with different risk factors in cancer patients, for example genetic factors (such as single nucleotide polymorphisms in genes related to inflammation, including the proinflammatory cytokines IL-1β, IL-6, and TNF-α), biological factors (such as alterations in the immune and neuroendocrine systems), psychosocial factors (such as depression, sleep disturbance, loneliness), and behavioral factors (such as physical inactivity and elevated body mass index) [12]. The prevalence of fatigue during treatment ranges from 25% to 99% depending on the population, treatment, and assessment method [11,16]. Additionally, research suggests that fatigue can predict shorter survival times [17], highlighting its significant impact on quality of life, given its correlation with survival outcomes [18]. In a study with colorectal cancer patients, fatigue was documented as a major cause of reduced quality of life (emotional and cognitive function), with over a third of long-term survivors reporting low quality of life after treatment [19].

Various approaches have been explored to address quality of life and fatigue, encompassing pharmacological, psychological, and exercise interventions. Of all of these, exercise emerges as a particularly promising strategy, with numerous documented benefits observed both during and after its implementation [12,20]. Exercise additionally mitigates treatment-related side effects, such as diminished bone mineral density and sarcopenia, which may otherwise predispose individuals to fractures and other musculoskeletal conditions [21], being also associated with lower mortality [22].

In a study by Shobeiri et al. [23], a 10-week aerobic exercise program significantly improved health in breast cancer patients, reducing fatigue compared to the control group. Additionally, Scott et al. [24] evaluated the efficacy of two different aerobic exercise regimens (fixed standard dosage and non-linear dosage) over 16 weeks, which were associated with modest improvements in cardiorespiratory fitness. Furthermore, Casla et al. [25] combined resistance exercise, strength training, and dietary counseling over 12 weeks, observing improvements in quality of life and isometric strength, with these benefits maintained at 6 months follow-up.

As aforementioned, numerous studies indicate that oncological patients can derive significant benefits from engaging in exercise. These benefits include a reduction in many of the negative consequences associated with cancer treatment, an enhancement in overall quality of life, and improvements in physical function, all while effectively mitigating fatigue [26]. Moreover, exercise has been linked to improved survival rates and a decreased risk of cancer recurrence [26,27]. Notably, increases in physical activity times of physical activity both before and after diagnosis have been associated with better survival outcomes across at least 11 types of cancer, underscoring the importance of advocating for global exercise guidelines following cancer diagnosis [28].

The existing literature predominantly focuses on medium to long-term interventions, covering periods ranging from 3 months to 18 months. Despite this extensive coverage, our literature search has revealed a lack of short-term exercise programs (≤6 weeks) [29], specifically tailored for cancer patients. Some of the benefits of short-term training would be to obtain improvements in physical condition without having many weeks of training in the case of having to undergo surgeries at short notice [30], improve glycemic control in patients with type 2 diabetes [31], or increase functional capacity, and decrease fatigue, anxiety, and depression in patients with multiple sclerosis, not improving their body mass index due to its short duration (4 weeks) [32]. On the other hand, studies have documented that as little as a single exercise session for 3 weeks can reduce anxiety-related symptoms in college students, making it more affordable for students compared to exercising for longer periods of time, especially during periods of high stress [33]. Moreover, a single or short-term exercise-induced protection can decrease the severity of myocardial injury caused by cardiac surgery or myocardial infarction, achieving immediate, clinically useful, and low-cost cardioprotection [34]. Therefore, although it has been widely demonstrated that long-term exercise causes very important physiological adaptations to reduce risk factors and improve health and physical condition, it has been shown that in certain cases it could be interesting to apply doses of exercise for a shorter time. Furthermore, there is a notable absence of interventions that integrate cardiorespiratory and strength exercises with stretching routines [35,36,37,38,39,40,41,42]. Therefore, this study aims to fill these gaps by assessing the impact of a six-week exercise program comprising aerobic, strength, and stretching exercises on quality of life, fatigue, and functional capacity in cancer patients.

2. Materials and Methods

2.1. Study Design

This is a quasi-experimental study, involving a group of 30 participants recruited through probabilistic convenience sampling, who were currently undergoing or had undergone chemotherapy, radiotherapy, or hormonal therapy within the last year. The nature of the treatment precluded masking its application. The exercise program lasted for six weeks and consisted of three distinct blocks: aerobic exercise, strength training, and stretching exercises. Each session lasted approximately one hour, with 25 min of aerobic exercise, followed by 20 min of strength training, and concluding with 15 min of stretching (Figure 1). Additionally, participants received reinforcement in standard self-care recommendations. Variables such as quality of life, fatigue, and functional capacity were assessed both at the beginning and upon completion of the intervention, which took place at the Rehabilitation Unit of the Infanta Leonor University Hospital.

2.2. Participants

Thirty women with breast cancer participated in the study (

Table 1. Descriptive data measurements for anthropometric variables, age, and BMI.

	Mean ± SD	(95% CI) Min–Max
Age (years)	55.9 ± 6.3	(45.6 to 62.7) 36–67
Weight (kg)	72.9 ± 10.5	(68.1 to 77.4) 55.6–99.4
Height (cm)	160.8 ± 6.6	(151.4 to 166.4) 151–181
BMI	28.2 ± 3.9	(22.6 to 29.2) 21.0–30.0
TREATMENT	n	(%)
Chemotherapy	26	(86.6)
Radiotherapy	29	(96.6)
Hormonal therapy	22	(73.3)
Completed treatment	19	(63.3)

Abbreviations: SD, standard deviation; CI, confidence interval.

). All of them met the inclusion criteria, which were as follows: (1) aged between 18 and 70 years, (2) diagnosed with oncological stage I, II, or III, who were currently receiving or had received chemotherapy, radiotherapy, or hormonal therapy in the last year, (3) scoring between 1 and 3 on the Eastern Cooperative Oncology Group (ECOG) scale, (4) having completed treatment and within one year of completion (surgery, chemotherapy, radiotherapy, or hormonal treatments: aromatase inhibitors, tamoxifen), (5) scoring between 1 and 3 on the Eastern Cooperative Oncology Group (ECOG) scale, (6) absence of musculoskeletal pathology, (7) absence of cardiopulmonary pathology limiting physical activity.

Additionally, none met any of the exclusion criteria, which were: (1) refusal to sign informed consent, (2) inability to read, understand, and complete questionnaires, (3) inability to read and understand an explanatory leaflet, (4) inability to understand and follow verbal instructions (e.g., illiteracy, dementia, or blindness), (5) significant neurological alterations affecting balance, coordination, or ataxia, (6) sports activity of moderate intensity greater than 120 min/week and/or previous experience in strength work, (7) symptomatic anemia, (8) fecal incontinence, (9) digestive stoma, (10) decompensated heart disease, (11) heart failure, (12) cardiotoxicity with hemodynamic repercussions, (13) uncontrolled arrhythmias, and (14) uncontrolled hypertension.

The study design was approved by the ethics committee of the Hospital Universitario Infanta Leonor and the Virgen de la Torre Hospital (internal code 012-23) and conducted in accordance with the Helsinki Declaration for human studies [43]. Data confidentiality of the participants was ensured in compliance with Organic Law 3/2018 of 5 December on Data Protection and Guarantee of Digital Rights. The study population was recruited by the oncology service of the hospital, which informed potential participants about the study and provided them with an information sheet and informed consent form (Figure 2). Subsequently, those patients who decided to participate attended an appointment where any doubts or questions were addressed, they signed the informed consent form in duplicate, and baseline measurements were taken. In the week prior to the start of the study, a training session was organized with all participants, where they were instructed on the prescribed exercise protocol, follow-up, frequency of controls, etc., and provided with a dossier containing all the information on the applied therapeutic exercise protocol. All participants were measured in the week before beginning the study and again in the week after completing the intervention.

2.3. Testing

Pre-Intervention Control. Independent variables (age, sex, height, weight, body mass index, cancer type, treatment received, and concomitant diseases) were recorded on an initial data collection sheet.

Blood oxygen saturation (SpO₂), systolic blood pressure (SBP), and diastolic blood pressure (DBP) pre- and post-exercise measurements were taken using standard procedures.

Six min Walking Test (6MWT). Before and after the exercise program, functional capacity was assessed using the 6MWT, which involved walking the greatest distance possible in 6 min. For this, two cones were placed 20 m apart, and participants walked along the route back and forth, ensuring they did not run [44].

Handgrip Test (HGT). Strength assessment was conducted using a manual handgrip strength test (HGT), using a manual hydraulic dynamometer (Jamar J00105, Lafayette Instrument Company, Lafayette, IN, USA) [45]. Three measurements of dominant hand grip strength were taken, with the participant performing the test from a seated position with the elbow flexed at 90°. In each measurement, participants squeezed the dynamometer as hard as possible for 5 s, with a 30 s rest between sets. The final grip strength value was the average of the three measurements.

Thirty s Sit-to-Stand Test (30s-STST). Lower limb strength was assessed using the 30s-STST, which measures the number of times a subject can go from sitting to standing in 30 s. Participants started from a seated position in a chair and had to perform the motion as many times as possible without using external supports and crossing their arms over their chest [46].

Quality of Life and Fatigue Questionnaires. Each participant completed the 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the 13-item Functional Assessment of Chronic Illness Therapy—Fatigue questionnaire (FACIT-F) [47,48]. Both questionnaires were completed under the same conditions, at the hospital, with a physiotherapist explaining how to complete them and remaining in the room in case any questions arose during their completion.

2.4. Exercise Program

The exercise program lasted 6 weeks, during which three non-consecutive sessions of 60 min each were held weekly, consisting of 25 min of aerobic exercise, 20 min of strength exercises, and 15 min of stretching.

2.4.1. Aerobic Exercise

Aerobic exercise was performed using elliptical machines, stationary bikes, and treadmills, with three phases: (1) a 5-min warm-up phase, (2) a 15-min maintenance phase, and (3) a 5-min cool-down phase. The workload for the elliptical machine in the first session was set at 5 W for the warm-up phase, 25 W for the maintenance phase, and 5 W for the cool-down phase. For the stationary bike, the workload in the first session was set at 20 W for the warm-up phase, 40 W for the maintenance phase, and 20 W for the cool-down phase. Treadmill exercise during the first session was performed at 3 km·h⁻¹ for the warm-up phase, 5 km·h⁻¹ for the maintenance phase, and 3 km·h⁻¹ for the cool-down phase. Exercise intensity was individually increased from the second session onwards, by adjusting speed and/or incline on the treadmill and resistance on the elliptical machine and stationary bike, aiming to maintain a perceived effort level between 4 and 6 on the Borg Category-Ratio-10 scale rating of perceived exertion (RPE) [49]. The exercise was performed using SCIFIT SXT7000 elliptical machines (SCIFIT Systems Inc, Tulsa OK, USA), SCIFIT ISO1000 stationary bikes (SCIFIT Systems Inc, Tulsa OK, USA), and Medisoft Clinical RAM 870a treadmills (MGC Diagnostics Corporation, Saint Paul, MN, USA) in the cardiac rehabilitation room of the Infanta Leonor University Hospital, using the “CARDIAC REHABILITATION ers.2 software” program from Ergoline (Ergoselect 200 K; Ergoline GmbH, Bitz, Germany) on all cardiovascular machines.

2.4.2. Resistance Training

Strength exercises were performed after completing the cardiorespiratory exercise. Resistance training was conducted using free weights, resistance bands, and bodyweight exercises. Two sessions of lower body and core strength training (quadriceps, hamstrings, glutes, and abdomen) were performed each week, interspersed with one session of upper body strength training (back, trapezius, deltoids, chest, biceps, and triceps). Each strength training session consisted of three sets of four exercises for either the core and lower body or the upper body. Repetitions for each of the three sets ranged from 10 to 15 (typically 10 for the first set, 12 for the second set, and 15 for the third set, but subject to variation based on demand and capacity), with an RPE of 7–8 out of 10. A rest period of 60 to 90 s was taken between sets to achieve an RPE of 4–5 before starting each new set.

2.4.3. Stretching Exercises

Stretching exercises were performed after strength exercises, with each participant spending 15 min performing stretches for the muscles worked during each session. The stretching protocol for each muscle group consisted of three sets of each stretching position, held for 30 s each.

2.5. Statistical Analyses

Based on the central limit theorem, a normal distribution of variables was assumed due to the large sample size (n = 30). To identify differences between physiological variables (SpO₂, SBP, DBP) pre- and post-test before and after the exercise program, a two-way repeated measures ANOVA was conducted for the time factor (pre- and post-exercise), with the interaction effect also observed. Additionally, the Levene statistic was applied to assess variance homogeneity. In the event of observing statistical differences in the interaction, the Bonferroni post hoc test was used to analyze pairwise differences. To analyze the variables from functional tests and the EORTC QLQ-C30 and FACIT-F questionnaires before and after the 6-week training, a paired samples t-test was employed. All data were expressed as mean (M), standard deviation (SD), and confidence interval (CI). Furthermore, percentages between different variables pre- and post-exercise were calculated using the following formula: ([post − pre]/pre × 100). The level of statistical significance was set at p < 0.05. The statistical package SPSS version 25.0 (SPSS, Chicago, IL, USA, III) was utilized.

3. Results

After completing the training program, significant differences were observed in SBP in both the Time and Group factors (p < 0.05), but not in the Time × Group interaction (p = 0.956) (

Table 2. Analysis of oxygen saturation, systolic blood pressure, and diastolic blood pressure before and after the test, and before and after the implementation of the exercise program.

Variable	Group	Pre-Exercise (M ± SD, 95% CI)	Post-Exercise (M ± SD, 95% CI)	p Time ηp2 SP	p Group ηp2 SP	p Group × Time ηp2 SP
SpO2 (%)	PRE-TEST	98.0 ± 1.1 (97.6–98.5)	97.8 ± 1.3 (97.4–98.2)	0.219 0.026 0.231	0.799 0.001 0.057	0.136 0.038 0.318
	POST-TEST	97.5 ± 1.3 (97.0–98.0)	97.9 ± 1.4 (97.4–98.3)
SBP (mmHg)	PRE-TEST	133.1 ± 16.6 *,‡ (127.7–138.5)	123.1 ± 12.7 ‡ (117.7–128.5)	<0.001 0.607 1.000	0.028 0.080 0.600	0.956 <0.001 0.050
	POST-TEST	149.1 ± 24.1 (141.4–156.9)	139.4 ± 17.6 (131.7–147.1)
DBP (mmHg)	PRE-TEST	85.1 ± 9.2 * (81.5–88.7)	76.9 ± 10.3 ‡ (73.3–80.5)	<0.001 0.217 0.976	0.024 0.085 0.624	0.004 0.136 0.845
	POST-TEST	85.9 ± 10.8 (81.9–89.9)	82.2 ± 10.9 (78.3–86.2)

SpO₂ = blood oxygen saturation; SBP = systolic blood pressure; DBP = diastolic blood pressure; * = significant difference between pre-exercise and post-exercise (p < 0.05); ‡ significant difference between pre-test and post-test (p < 0.05). M = mean ± SD = standard deviation; CI = confidence interval; η_p² = partial eta-squared; SP = statistical power.

). Analyzing pairwise comparisons, significant differences were found in SBP between pre-test and post-test, both pre-exercise and post-exercise (p < 0.001). However, statistical significance in SBP was only found in the pre-test after the implementation of an exercise program (p = 0.011). For DBP, significant differences were found in both the Time and Group factors and the Time × Group interaction (p < 0.05). Pairwise analysis revealed significant differences in DBP in the pre-test after the implementation of an exercise program (p = 0.002). Additionally, significant differences were observed between pre-test and post-test measurements of DBP post-exercise (p < 0.001).

Upon analyzing the results of functional capacity variables, significant improvements are observed in all variables following the implementation of the exercise program (p < 0.05) (

Table 3. Analysis of variables indicating functional capacity before and after implementation of the exercise program.

Variable	Pre-Exercise (M ± SD, 95% CI)	Post-Exercise (M ± SD, 95% CI)	p	Post-Exercise–Pre-Exercise (%)
6MWT (m)	527.5 ± 66.3 (502.7–552.2)	577.1 ± 79.0 (547.6–606.6)	<0.001 *	9.4%
RPE 6MWT	5.0 ± 1.7 (4.4–5.7)	4.3 ± 1.5 (3.7–4.9)	0.003 *	−14%
30s-STST (repetitions)	12.2 ± 3.0 (11.0–13.3)	14.2 ± 3.1 (13.0–15.3)	<0.001 *	16.4%
HGT (kg)	20.2 ± 9.8 (16.5–23.8)	22.9 ± 9.4 (19.4–26.3)	<0.001 *	13.4%

6MWT = six-minute walk test; RPE = rate of perceived exertion; 30s-STST = 30 s sit-to-stand test; HGT = handgrip test; * = significant difference between pre-exercise and post-exercise (p < 0.05); M = mean ± SD = standard deviation; CI = confidence interval.

).

Regarding the results of the FACIT-F questionnaire, significantly higher scores were obtained in fatigue scores after the exercise program (p < 0.05) (

Table 4. Fatigue FACIT questionnaire results before and after the exercise program.

Variable	Pre-Exercise (M ± SD, 95% CI)	Post-Exercise (M ± SD, 95% CI)	p	Post-Exercise–Pre-Exercise (%)
FACIT-Fatigue	32.5 ± 8.0 (29.5–35.5)	36.8 ± 7.3 (34.1–39.6)	0.002 *	13.2%

FACIT = Functional Assessment of Chronic Illness Therapy; * = significant difference between pre-exercise and post-exercise (p < 0.05); M = mean ± SD = standard deviation; CI = confidence interval.

). Since each of the 13 items on the scale ranges from 0 to 4, the possible score range is from 0 to 52, with 0 being the worst and 52 being the best. Therefore, before the exercise program, they had a score of 62.5% of the maximum score, and after, 70.8%.

Regarding the EORTC QLQ-C30 questionnaire (

Table 5. Results of the different areas and items of the EORTC QLQ-C30 questionnaire before and after the implementation of the exercise program.

Variable		Pre-Exercise (M ± SD, 95% CI)	Post-Exercise (M ± SD, 95% CI)	p	Post-Exercise–Pre-Exercise (%)
Global health status	Global health status	39.3 ± 21.7 (31.2–47.4)	52.5 ± 17.3 (46.1–59.0)	0.001 *	9.4%
Functional scales	Physical functioning	86.2 ± 13.9 (81.0–91.4)	85.5 ± 13.0 (80.7–90.4)	0.668	−14%
	Role functioning	67.8 ± 30.9 (56.3–79.4)	78.3 ± 25.5 (68.8–87.9)	0.008 *	16.4%
	Emotional functioning	68.6 ± 29.2 (57.7–79.5)	82.6 ± 14.1 (77.4–87.9)	0.004 *	20.4%
	Cognitive functioning	68.6 ± 26.5 (58.7–78.5)	87.2 ± 17.3 (80.7–93.6)	<0.001 *	27.1%
	Social functioning	73.9 ± 30.8 (62.4–85.4)	78.9 ± 24.3 (69.9–88.1)	0.196	6.8%
Symptom scales/items	Fatigue	38.4 ± 28.3 (27.8–49.0)	27.2 ± 18.2 (20.4–34.0)	0.010 *	−29.2%
	Nausea and vomiting	5.7 ± 8.2 (2.6–8.7)	2.8 ± 7.7 (−0.08–5.7)	0.160	−50.9%
	Pain	50.6 ± 31.3 (38.9–62.3)	35.0 ± 24.1 (26.0–44.0)	0.001 *	−30.8%
	Dyspnea	16.5 ± 22.6 (8.1–25.0)	7.7 ± 16.8 (1.5–14.0)	0.003 *	−53.3%
	Insomnia	48.8 ± 33.7 (36.3–61.4)	27.7 ± 29.2 (16.8–38.6)	0.002 *	−43.2%
	Appetite loss	13.3 ± 24.2 (4.3–22.4)	2.2 ± 8.4 (−0.9–5.3)	0.016 *	−83.5%
	Constipation	12.1 ± 18.5 (5.2–19.0)	13.2 ± 16.4 (7.1–19.3)	0.776	9.1%
	Diarrhea	7.7 ± 16.8 (1.5–14.0)	4.4 ± 11.4 (0.1–8.7)	0.372	−42.9%
	Financial difficulties	14.4 ± 27.2 (4.2–24.5)	75.5 ± 30.4 (64.2–86.8)	<0.001 *	424.3%%

* = significant difference between pre-exercise and post-exercise (p < 0.05); M = mean ± SD = standard deviation; CI = confidence interval.

), significantly higher scores were observed in the global health status scale (p < 0.05), as well as in the functional scale in the role functioning, emotional functioning, and cognitive functioning items (p < 0.05), indicating a higher quality of life and overall health level. Conversely, significantly lower scores were found in the fatigue, pain, dyspnea, insomnia, and loss of appetite items (p < 0.05). Additionally, there were significantly higher scores in the financial difficulties items (p < 0.05).

4. Discussion

To the best of our knowledge, this is the first study conducted in cancer patients where a 6-week program combining aerobic, resistance training, and stretching exercises has been implemented. Our findings suggest that despite its short duration, this program leads to improvements in quality of life and reduction in fatigue, as well as enhancement in muscle strength and functional capacity.

The quality of life of participants experienced a significant improvement without any recorded adverse events, with an increase of 9.4% in the global health status, a result consistent with previous studies conducted in similar populations [23,50,51]. However, it is worth noting that in all these studies, the programs were of longer duration.

Analyzing the results by areas and symptoms reveals encouraging outcomes. In the functioning area, there were notable improvements in role functioning (16.4%), possibly associated with gains in strength, endurance, and mobility observed at the end of our intervention and their transfer to daily activities. Emotional role improved by 20.4%, likely due to the release of serotonin and beta-endorphins during physical activity, as indicated in previous studies [52], with a positive impact on anxiety and stress. Cognitive function increased even more significantly, by 27.1%. Numerous studies support our findings, indicating that aerobic exercise leads to improvements in brain function and cognition after 6 weeks [53,54,55,56].

Regarding symptomatology, significant improvements were notable post-intervention. Pain decreased by 30.8%, possibly due to the secretion of endogenous opioids and serotonin associated with physical activity. Dyspnea reduced by 53.3% as a consequence of positive adaptations resulting from aerobic training. Fatigue and insomnia decreased by 29.2% and 43.2%, respectively, possibly related to cortisol modulation due to physical exercise [57]. Anorexia also saw notable improvement, possibly caused by increased energy expenditure and nutrient demand. However, it is noteworthy that financial difficulties increased, a trend consistent with other studies in cancer patients [23], without a defined cause.

Regarding fatigue, one of the most common symptoms in cancer patients [11] closely related to quality of life [18], there was a 13.2% improvement in FACIT-F and a 29.2% improvement in the fatigue-related symptoms in the EORTC QLQ C-30 questionnaire. These improvements were also observed in other therapeutic exercise programs measured with these or other instruments [23,24,25]. In addition to the previously mentioned aspects, we believe that physical exercise could exert a compensatory action on factors directly related to fatigue. These factors may include catabolic effects produced by tumor processes, resulting in muscle tissue loss exacerbated by the adverse effects of immunosuppressants. This leads to a decrease in myofibrillar mass, alteration of aerobic metabolism, and reduced capillarization [58].

The results regarding the improvement in strength and functional capacity of the patients align with those reported in other studies [25,39,59]. In these studies, a combined exercise of strength and cardiorespiratory endurance was also implemented. However, the duration of those exercise programs ranged from 12 weeks to 18 months. In contrast, in this study, physical function improved with just a 6-week exercise program conducted three days a week. Thus, positive outcomes were achieved in half the time compared to other studies [25,59]. These results may primarily be attributed to the choice of exercise program. A combined strength and endurance program yields better results in aerobic endurance capacity, patient-reported physical functioning, bodily pain, fatigue, and endocrine symptoms compared to a standard aerobic exercise dose (25–30 min) [60]. Furthermore, in other programs where aerobic exercises were implemented for 12 to 16 weeks [24,40], although they were safe and tolerable, only modest improvements were achieved in cardiorespiratory fitness in early-treated breast cancer patients [24], or improvements in cardiorespiratory fitness without any conclusive evidence on the effect of cardiotoxicity in HER2-positive breast cancer patients treated with adjuvant therapy with trastuzumab [40].

Another factor that may have contributed to improvements in muscle strength was the intensity of the prescribed exercise. Participants were encouraged to control intensity, aiming for an RPE between 7 and 8 (very hard) out of 10 in the final repetitions of each strength exercise. This is because the American College of Sports Medicine, in the ACSM Guidelines for Exercise and Cancer [61], considers work performed at this threshold as vigorous physical activity, recommending 2 to 3 days of exercise per week at this intensity, performing two sets of eight to 12 repetitions each. Regarding the intensity of cardiorespiratory exercise, it was rated between 4 and 6 out of 10 (considered moderate), consistent with the intensity recommended by the ACSM for this type of patient.

In other studies where RPE was used to control intensity (both in strength and aerobic exercise), the intensity started at a moderate level in the first month and gradually increased over the weeks, reaching a level between hard and very hard in the third month [25]. In our study, we chose to prescribe high intensity from the beginning of the program to achieve adaptations in a shorter period.

The inclusion of stretching exercises in almost one-third of the daily session was due to several reasons: (1) the positive effect of stretching on adaptations of endothelial function and muscle blood flow in elderly rats, increasing microvascular volume, the number of capillaries per muscle fiber, levels of hypoxia-induced factor-1α, vascular endothelial growth factor, and endothelial nitric oxide synthase [62], (2) increased shoulder range of motion and a decrease in chest tightness and pain after breast cancer surgery [63,64], (3) reduction in tumor growth due to restoration of cytotoxic immunity by reversing the impairment of cytotoxic CD8+ T lymphocytes and activation of T cells, which play a central role in immune defense [65], (4) furthermore, resolvin D1 (RvD1) and resolvin D2 (RvD2), pro-resolving lipid mediators (SPM) with anti-inflammatory properties [66,67], were significantly higher in stretched mice compared to control mice [65,66], reducing acute inflammation. Therefore, improvements in quality of life and reduction in fatigue could be attributed to the performance of exercises.

Finally, we would like to point out that based on the available evidence, it is likely that the supervision and intensity of the sessions, rather than the duration of an exercise program, justify the improvements observed in this type of patient. Therefore, we find improvements related to the quality of life [24,25,35,50,68], fatigue [23,24,45], or functional capacity [25,59] in interventions that are fully supervised with an average duration of 12 to 24 weeks. However, these improvements are not observed in other longer programs (18 to 52 weeks) characterized by less rigorous supervision [69], telephone supervision [70], or evolution from supervision to autonomous work, either progressively [42] or immediately [41]. Therefore, we believe that a shorter duration program that is rigorously supervised will be effective in improving the quality of life of cancer patients, thus allowing the optimization of human and material resources available to adequately respond to the constant increase in the incidence of these types of pathologies.

The most important limitation of the study is not having a control group with which to compare the results obtained. Another limitation is that the residual effect of the exercise (3 months later, 6 months later, etc.) is not assessed either. However, this opens up new lines of research aimed at controlling the results and seeing the effect of exercise in short-term exercise programs.

5. Conclusions

A properly supervised therapeutic exercise protocol with vigorous intensity, lasting for six weeks, including resistance training, endurance, and stretching exercises, can be safe and effective in cancer patients. This can lead to significant improvements in quality of life and reduction in fatigue, as well as enhancing muscle strength and functional capacity. The absence of adverse events during the intervention supports the feasibility and safety of this protocol.