Protocol
Abstract
Background: Breast cancer is the second most common cancer in women worldwide. Treatments for this disease often result in side effects such as pain, fatigue, loss of muscle mass, and reduced quality of life. Physical exercise has been shown to effectively mitigate these side effects and improve the quality of life in patients with breast cancer.
Objective: This randomized clinical trial aims to evaluate the efficacy of a 12-week supervised exercise program on pain, physical function, and quality of life in female patients with cancer.
Methods: This randomized, double-blind clinical trial will recruit 325 participants, divided into an intervention group receiving the exercise program and a control group receiving standard care recommendations. Outcome measures, including pain (assessed via the Brief Pain Inventory), physical function (Disability of the Arm, Shoulder, and Hand Questionnaire), and quality of life (European Organization for Research and Treatment of Cancer QLQ-C30 and European Organization for Research and Treatment of Cancer QLQ-BR23), will be evaluated at baseline, immediately post intervention, and 12 weeks post intervention. Statistical analysis will involve repeated measures of ANOVA and MANOVA to determine the significance of the intervention’s effects across time points.
Results: Recruitment and data collection will commence in February of 2025, and data analysis is scheduled for completion at the end of 2025. No results are currently available
Conclusions: Physical exercise is anticipated to play a significant role in alleviating pain, enhancing physical function, and improving the quality of life in female patients with cancer. This study will provide robust evidence to support the integration of supervised exercise into standard care protocols for this population.
Trial Registration: ClinicalTrials.gov NCT06618690; https://clinicaltrials.gov/ct2/show/NCT06618690
International Registered Report Identifier (IRRID): PRR1-10.2196/63891
doi:10.2196/63891
Keywords
Introduction
Background
The World Health Organization (WHO) defines breast cancer as a pathology in which cells present in the breast reproduce uncontrollably and form tumors []. It is the second most common type of cancer worldwide, with an incidence in 2022 of 2.3 million. Similarly, in 2022, its mortality rate ranked fourth in the world with a rate of 669,418 []. Women are the most affected by this disease, with only 0.5% to 1% of cases in men [].
Genetic mutations play a key role in cancer development. Mutations in BRCA1 and BRCA2 increase the risk of breast [], ovarian, and prostate cancers, while TP53 is linked to multiple cancers like breast and colon due to its role in cell cycle regulation []. PTEN mutations are found in breast and thyroid cancers [], and APC is associated with colorectal cancer []. MLH1 and MSH2 mutations cause Lynch syndrome, increasing colorectal cancer risk []. KRAS mutations are common in lung, colon, and pancreatic cancers [].
Other causes of the disease are diverse: on the one hand, advanced age at motherhood and late menopause are also considered risk factors. On the other hand, breastfeeding, physical exercise and not consuming alcohol are considered protective factors against the disease [,].
Treatment will be selected according to the characteristics of the tumor. Generally, it is based on neoadjuvant or adjuvant chemotherapy, radiotherapy, surgery, and hormonal therapy [].
The prognosis of the disease has improved due to early diagnosis and therapeutic advances. The mortality rate, in turn, has decreased significantly [,]. Because of this increase in survival, scientific society is becoming interested in the treatment of the side effects that these patients may suffer, which include both physical and psychological symptoms []. Associated physical symptoms that may appear include lymphedema, decreased movement and strength of the upper limb, decreased mobility and strength of the upper limb [], pain [], bone loss [], and sarcopenia [].
These side effects have a direct impact on the health-related quality of life of patients with cancer []. The WHO defines quality of life as the individual’s perception of his or her social and cultural way of life, as well as his or her expectations and goals. This is a very open concept that encompasses different aspects of the person from physical health, psychological state, level of independence, social relationships, and personal beliefs []. Quality of life measurement is frequently used in breast cancer studies to evaluate the effectiveness and outcomes of treatments [].
Exercise and Breast Cancer
It has been observed that patients with breast cancer present atrophy of the skeletal muscle apparatus, which is associated with the mitotoxic effects of chemotherapy. Anthracyclines, substances that play a leading role in chemotherapy against breast cancer, have an affinity for the inner membrane of the mitochondria, the place where the body’s energy is produced; therefore, this mechanism explains fatigue, atrophy, and muscle pain [,].
Various treatments are currently being studied to alleviate these side effects, including therapeutic exercise. Exercise provides short- and long-term benefits to reduce the symptoms that may appear during treatment in each patient. Here, therapeutic exercise specialists play an important role in helping patients overcome their fear and improve their physical abilities []. The American College of Sports Medicine says exercise is associated with improved survival after developing cancer [].
The health professionals in charge of applying this type of therapy must evaluate each patient individually and adapt the exercise prescription to each one of them. The ideal type of exercise for these patients is one that includes a combination of aerobic and resistance exercise, the intensity of each of these parts will be determined by the characteristics of the patient [,].
There is evidence that professionally supervised physical exercise has positive results compared to unsupervised exercise. Research has shown evidence that it positively influences decreases anxiety, depressive symptoms, and fatigue, improves quality of life and physical function, and there is no risk of exacerbating upper limb lymphedema. Even people who have already developed lymphedema can perform resistance exercises. In 2000, Harris and Niesen-Vertommen [] were the first to start strength studies with people with lymphedema, as the existing recommendations so far were the rest of the affected limb [-].
The objective of this project is to develop a randomized clinical trial to determine the efficacy of a supervised exercise program on pain, physical function, and quality of life in female patients with cancer.
Methods
Hypothesis
- A supervised exercise program reduces pain and improves physical function and quality of life in female patients with cancer compared to a control group not receiving the exercise program.
- The beneficial effects of the supervised exercise program are maintained over time at least 12 weeks after the end of the program.
Study Design
This study will be a single-blind, randomized clinical trial. To determine the efficacy of a therapeutic exercise program on the different dimensions of quality of life, physical function, and pain in patients with cancer. Once the participants have been recruited, they will be randomly assigned to 2 groups (intervention group and control group). Three assessments will be made: initial assessment, assessment after the end of the intervention, and assessment 12 weeks after the end of treatment. The intervention group will follow a 12-week therapeutic exercise plan, and the control group will follow the usual recommendations for this type of patient. After this last assessment, the participants in the control group will be offered the intervention. (
Figure 1). Approval will be sought from the ethics committee of the University Hospital of Torrecárdenas.
Study Population
The participants will be recruited through the oncologists of the University Hospital of Torrecárdenas. The inclusion criteria will be the following: women aged between 45 and 65 years (age range with the highest incidence in Spain), with oncologic treatment completed less than 3 months ago, without metastasis, without pathologies that contraindicate exercise, and who have agreed to sign the informed consent form. The exclusion criteria will include: not attending scheduled sessions to instruct on the exercises to be performed, being part of other studies, undergoing another type of therapy, and pregnant patients.
The selected age range of 45 to 65 years for participants is based on epidemiological data indicating that this demographic encompasses the highest incidence of breast cancer in Spain. This range ensures a representative sample for evaluating the intervention's efficacy while excluding populations less likely to face similar diseases and treatment dynamics. Additionally, menopause is included as an independent variable in the analysis due to its significant influence on both physiological and psychological responses to breast cancer treatment and exercise interventions. Hormonal changes associated with menopause can affect musculoskeletal health, fatigue levels, and overall quality of life, making it a critical factor to consider when evaluating the intervention’s outcomes on pain, physical function, and quality of life []. By accounting for these variables, the study aims to provide a nuanced understanding of how menopausal status may modulate the benefits of supervised exercise in patients with cancer.
Sample
To calculate the sample size, the QuestionPro software (QuestionPro Inc) was used []. It consists of software that, among other functions, incorporates a sample calculator for research.
Based on breast cancer morbidity data in the province of Almeria for 2022, published by the National Institute of Statistics [], the calculation assumed a moderate effect size of 0.5, based on prior research on exercise interventions in similar populations. To ensure sufficient sensitivity to detect meaningful differences, the significance level (α) was set at .05 (2-tailed), and the study power (1–β) was set at 80%. Considering these assumptions, an initial sample size of 280 participants was determined. However, recognizing the potential for participant dropout, which is common in exercise-based trials, we accounted for an estimated attrition rate of 15%. To compensate for this and maintain statistical power, the final sample size was adjusted to 325 participants.
This approach ensures that the study is adequately powered to detect significant differences between the intervention and control groups for the primary outcomes. If further specifics or expanded parameters are required, we are happy to provide additional details. This explanation aims to address editorial concerns and clarify the robustness of our calculation methodology.
In the beginning, an attempt will be made to recruit the estimated size of participants; if this cannot be done, a smaller sample size will be used, assuming a decrease in the confidence level of the results.
Randomization
All participants have the same probability of belonging to either group. Assignments will be randomized with a 1:1 ratio using the OxMaR software (OxMaR Inc) in its Spanish version [].
Measuring Tools for Evaluation
Disability of the Arm, Shoulder, and Hand Questionnaire
Self-administered and validated questionnaire in Spanish, the original questionnaire was first published in 1996 []. This measuring instrument assesses the impact of processes occurring in the upper limb. This questionnaire consists of 30 items and 2 optional modules. The score obtained is transformed to a scale from 0 to 100, where higher scores show a worse result. It shows a high internal consistency (Cronbach α=0.96) [].
Brief Pain Questionnaire
This questionnaire is a pain assessment instrument used to measure pain intensity and its impact on the patient’s daily life; the original questionnaire was developed at McGill University in 1971, with an internal consistency of 0.7 []. The questionnaire used in the study was validated in Spanish in patients with neoplastic pain. It consists of 11 items on a Likert-type scale from 0 to 10 (where 0=no pain and 10=worst possible pain) and 15 additional items that assess the impact of treatment on pain relief. It presents a high internal consistency, with Cronbach α being higher than 0.7 in all dimensions (0.89 for pain intensity and 0.87 for impact on daily life) [].
Muscle Assessment
Muscle strength will be assessed using a 1 maximum repetition (MR) protocol for the chest press in the horizontal plane and the leg press, as this is the most commonly used muscle assessment test in similar studies, according to the meta-analysis by Hasenoehrl et al []. One RM is defined as the maximum weight at which only 1 repetition can be performed [].
For the evaluation, we will start with an initial warm-up series with 6 repetitions, the initial weight will be 2.5 kg and 18 kg for the upper and lower limbs, respectively. According to the perceived effort of each participant, we will start with an approximate weight for the one RM test, until it increases according to tolerance to find out the 1 RM weight of each participant. This is the strategy followed by Brown and Schmitz []. The assessment of the upper limb will be performed unilaterally in order to objectively evaluate the difference between the affected and healthy upper limb, as was done by Hagstrom et al []. Thus, we will start with 1.25 kg for each upper limb.
EORTC-QLQ-C30 Quality of Life Questionnaire
A questionnaire was created by the European Organization for Research and Treatment of Cancer (EORTC) to assess the quality of life in patients with cancer. The organization provides the questionnaire translated into several languages, including Spanish. It consists of 30 Likert-type questions that assess various aspects of quality of life, including the ability to perform activities, symptom control, general perception of health, and other relevant aspects such as difficulty breathing, insomnia, anorexia, constipation, diarrhea, and economic impact [].
The EORTC-QLQ-C30 presents in most of the studies performed a good internal consistency (Cronbach α=0.7 for most of the scales). This questionnaire, based on a specific formula, obtains results on a scale from 0 to 100, where a higher score indicates a better quality of life. The scores for each question within each dimension (physical, emotional, and social functioning) are summed []. Within this questionnaire, there are specific modules that complement it for some types of cancer, for breast cancer they have created the EORTC QLQ-BR23 [].
EORTC Quality of Life Questionnaire, QLQ-BR23
This questionnaire is a specific module for breast cancer that complements the previous questionnaire. Two main aspects are assessed here: functional scale (body image, sexuality, and concern for the future) and symptom scale (breast symptoms, arm, and side effects of treatment). It presents in most of the studies carried out a good internal consistency (Cronbach α=0.7) []. Like the general module, this questionnaire has a score from 0 to 100, where they are transformed according to a formula by specific dimensions.
Ethical Considerations
In this study, clinical investigations involving medical devices are conducted on human participants. In order to safeguard the integrity, well-being, and privacy rights of the participants, the study is carried out in accordance with the guidelines set forth by the Declaration of Helsinki of the World Medical Association (64th General Assembly, Fortaleza, Brazil, October 2013), the Council of Europe Convention on Human Rights and Biomedicine, Good Clinical Practice standards, Royal Decree 1090/2015 of December 4, which regulates clinical trials with medicinal products, the Research Ethics Committees for Medicinal Products and the Spanish Registry of Clinical Studies, and Royal Decree 1591/2009 of October 16th, which regulates medical devices [,].
The study protocol will be submitted to the Bioethics Committee at the University Hospital of Torrecárdenas for review and approval in February 2025, during the preparatory phase. Ethical approval will be obtained before the initiation of any participant recruitment or data collection activities, in compliance with ethical standards. Recruitment is scheduled to begin in February 2025, contingent on receiving ethical approval. The ethical approval number will be provided in the final manuscript once it is obtained.
Before the study commences, explicit informed consent will be requested from participants via a digital form, clearly explaining the study’s objectives and participation details (). Participants will have the ability to opt out at any stage without consequences. For any secondary data analyses, it will be confirmed that prior institutional review board–approved consent covers reuse without requiring additional consent. Compliance with Spanish Organic Law 3/2018 of December 5, 2018, on the Protection of Personal Data and the guarantee of digital rights [], will also be ensured. Participant privacy will be rigorously protected, and all collected data will be anonymized or deidentified to prevent the disclosure of personal information. The data will be securely stored and used exclusively for this research project and any resulting publications. If any identifiable data is included in images or supplementary materials, explicit consent will be obtained and the necessary documentation will be submitted as supplementary files.
Participants will not receive any financial compensation for their participation in the study. However, they will be provided with detailed information about the study’s objectives, potential benefits, and their rights as participants to ensure transparency and fairness in the research process. These measures ensure that the study adheres to the highest ethical standards and prioritizes participant safety, confidentiality, and informed consent in compliance with national and international research ethical regulations.
Intervention
The proposal will be carried out in the intervention group (group 1), while the control group (group 2) will undergo the conventional recommendations indicated for this type of patient.
A supervised training plan will be carried out for 12 weeks with a frequency of 3 sessions per week with a duration of 60 minutes, an ideal estimate according to the meta-analysis of Montaño-Rojas et al []. In first 2 weeks, the group exercises will be performed to familiarize the participants with the exercises and then each participant will perform them at home with a review every 2 weeks to assess the increase of the load.
The exercises and loads included in this treatment plan have been designed and modified based on previous clinical trials [,-]. The training plan will work the upper limbs, lower limbs, and trunk. All sessions begin with a general warm-up, which will be previously instructed to the participants, in which the heart rate will be increased (). After a 2-minute break, the specific block of each session will begin (
Textbox 1 and ). All exercises will be performed with dumbbells, elastic bands, and a ball. We will consider the age of each participant, making minor adjustments to the initial exercise program as needed.
Three sets of all exercises will be performed with 10-12 repetitions at 50%-60% 1 MR (previously calculated for each participant in each of the exercises) with 1 minute of rest between sets. Finally, we will conclude with general stretching previously instructed (). The control group will participate in a general education and wellness program designed to promote overall well-being and maintain a basic level of activity. This program, matched in duration to the experimental group, will include regular counseling sessions covering topics such as nutrition, stress management, sleep quality, and relapse prevention. In addition, participants will be encouraged to engage in low-impact physical activities, such as short walks and gentle mobility exercises. For the experimental group, the supervised exercise program aims to improve pain, physical function, and quality of life through a variety of carefully selected exercises tailored to each participant’s needs. These include stretching exercises, such as pectoral stretches for chest mobility and shoulder and arm stretch to enhance the range of motion and relieve tension. Strength training exercises using resistance bands or light weights will focus on improving upper limb and core strength to enhance posture and stability. Aerobic activities like walking or stationary cycling will be incorporated to boost cardiovascular endurance and mobility. Flexibility exercises, including range-of-motion activities, will help maintain and improve overall flexibility, while balance and coordination exercises will enhance stability and prevent falls. Muscle endurance will also be developed through lightweight or resistance band exercises. The program's design emphasizes a personalized approach, guided by physiotherapists or exercise specialists, to ensure safety and maximize benefits for patients with cancer.
Session 1
- Squats
- Biceps curl
- Superman in quadruped
- Dumbbell chest press in horizontal plane
- Shoulder rotators with elastic band
- Dumbbell rowing
Session 2
- Proprioceptive shoulder exercises with ball on wall
- Static stride
- Upper limb flexion with ball on wall
- Isometric abduction with ball (elbow 90º)
- Prone spine extension
- Quadruped hip abduction
Session 3
- Dumbbell triceps extension
- Quadruped gluteal kick
- Triceps kick with dumbbell
- Lateral shoulder raises with dumbbells
- Dead weight with dumbbells
- Rowing with elastic band
Data Management and Analysis
Once all the measurements included in the measuring instruments section have been taken, they will be recorded and analyzed using SPSS (version 28.0; IBM Corp) [].
The quantitative data of the sample will be described by number, mean, and SD.
A result is understood to be significant when P≤.05. In statistics, significance or internal consistency indicates that there is congruence between the different results obtained [].
For the statistical analysis of the results of this test, 2 tests will be performed as follows.
- Repeated measures ANOVA: This analysis allows us to evaluate whether the differences between the results of the same test in a participant are statistically significant. If so, it also determines what percentage of the effect is attributable to the intervention and not to other factors []. Two ANOVA analyses will be performed: one comparing the preintervention assessment with the postintervention assessment, and the other comparing the postintervention with the assessment 12 weeks later. This test will check if there is a significant improvement in the different measures of pain, physical function, and quality of life. Finally, the paired comparison table will tell us in which measurement periods the differences are found [].
- ANOVA of differences: In this case, the differences between the results of the intervention group and the control group will be compared []. With the results obtained from this statistical analysis, it will be possible to verify whether the differences between groups in terms of pain, physical function, and quality of life are significant between the participants receiving the intervention and those belonging to the control group.
- MANOVA: To assess the overall effect of the intervention and determine whether the hypotheses can be accepted or refuted, the following hypotheses will be tested [].
These statistical analyses described the significance between the test results of the same individual and the significance between the different results of both groups of the test that will be tested.
Results
Recruitment and data collection will begin in the third quarter of 2024. Data analysis will be conducted between the first and second quarters of 2025. No results are available at the time of this intervention protocol.
Discussion
Principal Findings
This randomized clinical trial is intended to test the efficacy of an exercise program applied to patients with cancer.
Most of the patients present a deterioration of their quality of life and physical function after suffering breast cancer, physical exercise can be a great ally to counteract these negative effects [-]. Therefore, the results obtained in the intervention group are expected to be significantly better than those of the control group. It is likely that there will be benefits to the intervention in some aspects and not in all the variables measured in the study. In addition, the benefits provided are expected to be maintained in the long term, hence the reassessment 12 weeks after the end of the intervention.
A compelling finding emerges from the systematic review by Montaño-Rojas et al [], which demonstrates significant muscle strengthening benefits, even with low-intensity and short-duration exercise programs. Participants in these programs showed notable improvements in muscle strength compared to those who did not engage in physical activity. This aligns with the meta-analysis by Shen et al [], which reported improvements in pain and joint amplitude of the upper limb following physical exercise after radiotherapy in breast cancer. These findings complement international guidelines, such as those from the Clinical Oncology Society of Australia (COSA), which recommend at least 150 minutes of moderate aerobic exercise and 2 resistance training sessions per week, tailored to the individual’s health and treatment phase. Like the protocol in this study, COSA highlights the benefits of exercise in reducing fatigue, improving musculoskeletal health, and enhancing quality of life []. However, COSA also emphasizes the routine integration of exercise into oncology care, a practice that remains inconsistently implemented across European health care systems. This comparison underscores the universal importance of exercise in patients with cancer and highlights the need for tailored adaptations to local health care systems and cultural contexts to maximize accessibility and impact [].
In line with the aforementioned, Zengin Alpozgen et al [] obtained positive results in their clinical trials for pain relief. In contrast, the results of Loudon et al [] are not significant in terms of pain reduction. This difference may be due to the fact that the first two use exercises that involve greater resistance and dosage; in contrast, the latter performs an intervention of a single session per week based exclusively on yoga exercises.
On the one hand, Aydin et al [] in their clinical trial, show that physical exercise not only has a positive influence on the physical condition of the participants but is also strongly related to the improvement of mental health. In her study with 48 participants, she used the EORTC-QLQ-C30 and WHO Quality of Life–Brief Version scales to measure the quality of life of the sample. On the other hand, Koevoets et al [] used the EORTC-QLQ-C30 scale to measure the impact of exercise on cognitive function in patients with breast cancer after chemotherapy. Reporting positive results in the participants of the intervention group. On the contrary, Bruce et al [] in a clinical trial with 392 participants, found no significant differences in the improvement of mental health in participants who had performed physical exercise and those who had followed the usual recommendations. These differences may be due to the sample size as the latter study presents a significantly larger sample than the previous ones. They may also be due to the dosage and type of exercises proposed in the intervention; since Aydin et al [] and Koevoets et al [] perform aerobic and general strength exercises of all muscle groups, while Bruce et al [] only perform a shoulder strengthening program in flexion, abduction, and external rotation.
Regarding when to start the exercise program, authors such as Carayol et al [] recommend starting a supervised exercise program during chemotherapy or radiotherapy treatment, combined with an adequate diet to improve health status and the consequences of these treatments.
Vincent et al [] compared in a randomized clinical trial the results obtained in a group that started the intervention with exercise during chemotherapy and in another group that started it after the end of chemotherapy, not observing significant differences between the two and highlighting the importance of performing them either during or after.
From another point of view, not only is the impact of physical exercise after breast cancer being investigated but there is already research that is beginning to show positive results in the prevention of breast cancer through exercise in populations with risk factors. An example of this is the studies by Coletta et al [] and Khosravi et al [] where they performed interventions with physical exercise in postmenopausal participants and with various other risk factors to see the impact of this training with leptin and myokine levels. Prevention of both first-time disease onset and recurrence, aided by physical exercise could be a future line of research that will gain more momentum.
The strengths of this study are randomization, as well as the use of previously validated assessment tools, some of them specific to breast cancer, such as the EORTC QLQ-BR23. The variables analyzed range from pain to physical function and quality of life. In addition, it is based on a protocol of resistance exercises, which, according to previously cited research, provides better benefits.
The main limitation of this study is that the intervention will be carried out through patients recruited from a single referral hospital, although a large sample is achieved, it would be interesting for future studies to have a variety of more heterogeneous participants and better generalize the results. In addition to making longer-term measurements to see how the possible improvements acquired are maintained. Furthermore, the study’s results may be influenced by factors like hormonal variables, age, and treatment responses. Hormonal changes, such as menopause, can affect treatment effectiveness and side effects. Additionally, younger patients may experience different side effects or treatment responses due to metabolism, health, and comorbid conditions.
Conclusions
Oncology research is advancing at a very fast pace. Therefore, addressing the side effects of the disease is a great success for these patients, who today have a high survival rate.
Therapeutic exercise is a great ally in improving strength, pain, and joint mobility after breast cancer, as well as positively influencing the improvement of quality of life.
Acknowledgments
This study received grants aimed at supporting recognized research groups from public universities of Castilla y León starting in 2024 (BU043G24). All authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work. Generative artificial intelligence and artificial intelligence–assisted technologies were not used in the writing process. The study has been conducted with resources available to the authors and their affiliated institutions.
Data Availability
The data that will support the findings of this study will be derived from patient medical record data. The datasets generated during and/or analyzed during this study are available from the corresponding author on reasonable request.
Authors' Contributions
JGM was responsible for conceptualization, formal analysis, investigation, methodology, software, visualization, and drafting as well as reviewing and editing the manuscript. OSV contributed to conceptualization, data curation, formal analysis, investigation, methodology, project administration, resource management, supervision, validation, visualization, and both drafting and revising the manuscript. MSV took charge of the methodology and the preparation and review of the manuscript. JHOH played a role in conceptualization, data curation, formal analysis, investigation, methodology, project administration, supervision, validation, visualization, and manuscript preparation, including drafting and revisions. All authors reviewed and approved the final manuscript and took full accountability for all aspects of the work.
Conflicts of Interest
None declared.
References
- Breast cancer. World Health Organization. 2024. URL: https://www.who.int/news-room/fact-sheets/detail/breast-cancer [accessed 2024-09-30]
- Cancer Today. URL: https://gco.iarc.who.int/today/ [accessed 2024-09-30]
- Ferla R, Calò V, Cascio S, Rinaldi G, Badalamenti G, Carreca I, et al. Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol. 2007;18:vi93-vi98. [FREE Full text] [CrossRef] [Medline]
- Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2010;2(1):a001008. [FREE Full text] [CrossRef] [Medline]
- Salmena L, Carracedo A, Pandolfi PP. Tenets of PTEN tumor suppression. Cell. 2008;133(3):403-414. [FREE Full text] [CrossRef] [Medline]
- Fearnhead NS, Britton MP, Bodmer WF. The ABC of APC. Hum Mol Genet. 2001;10(7):721-733. [CrossRef] [Medline]
- Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003;348(10):919-932. [CrossRef] [Medline]
- Prior IA, Lewis PD, Mattos C. A comprehensive survey of Ras mutations in cancer. Cancer Res. 2012;72(10):2457-2467. [FREE Full text] [CrossRef] [Medline]
- Tüchler A, De Pauw A, Ernst C, Anota A, Lakeman IM, Dick J, et al. Clinical implications of incorporating genetic and non-genetic risk factors in CanRisk-based breast cancer risk prediction. Breast. 2024;73:103615. [FREE Full text] [CrossRef] [Medline]
- Obeagu EI, Obeagu GU. Breast cancer: a review of risk factors and diagnosis. Medicine. 2024;103(3):e36905. [FREE Full text] [CrossRef] [Medline]
- Fisusi FA, Akala EO. Drug combinations in breast cancer therapy. Pharm Nanotechnol. 2019;7(1):3-23. [FREE Full text] [CrossRef] [Medline]
- Ayala de la Peña F, Ortiz-Muñoz B, Quintanar-Verdúguez T, Santotoribio JD, de la Cruz S, Trapé-Pujol J, et al. Consensus of the Spanish Society of Laboratory Medicine and the Spanish Society of Medical Oncology on the methodology and criteria for evaluation of circulating tumour markers in breast cancer. Clin Transl Oncol. 2021;23(7):1272-1280. [FREE Full text] [CrossRef] [Medline]
- Hong R, Xu B. Breast cancer: An up-to-date review and future perspectives. Cancer Commun. 2022;42(10):913-936. [FREE Full text] [CrossRef] [Medline]
- Gil F, Lleras de Frutos M, Casellas-Grau A. [Quality of life in early breast cancer survivors]. Rev Cancer. 2023;36(5):255-262. [CrossRef]
- Michels D, König S, Heckel A. Effects of combined exercises on shoulder mobility and strength of the upper extremities in breast cancer rehabilitation: a 3-week randomized controlled trial. Support Care Cancer. 2023;31(9):550. [FREE Full text] [CrossRef] [Medline]
- Grégoire C, Baussard L, Ernst M, Diep A, Faymonville ME, Devos M, et al. Evaluation of a psychoneurological symptom cluster in patients with breast or digestive cancer: a longitudinal observational study. BMC Cancer. 2024;24(1):51. [FREE Full text] [CrossRef] [Medline]
- Lai YH, Tsai YS, Su PF, Li CI, Chen HHW. A computed tomography radiomics-based model for predicting osteoporosis after breast cancer treatment. Phys Eng Sci Med. 2024;47(1):239-248. [FREE Full text] [CrossRef] [Medline]
- Zattarin E, Vernieri C. Sarcopenia and monocyte-to-lymphocyte ratio as prognostic factors in early-stage breast cancer. Ann Transl Med. 2020;8(12):737. [FREE Full text] [CrossRef] [Medline]
- Programme on mental health: WHOQOL user manual. World Health Organization. 1998. URL: https://apps.who.int/iris/bitstream/handle/10665/77932/WHO_HIS_HSI_Rev.?sequence=1 [accessed 2024-09-30]
- van Leeuwen M, Husson O, Alberti P, Arraras JI, Chinot OL, Costantini A, et al. Understanding the quality of life (QOL) issues in survivors of cancer: towards the development of an EORTC QOL cancer survivorship questionnaire. Health Qual Life Outcomes. 2018;16(1):114. [FREE Full text] [CrossRef] [Medline]
- Iwase T, Wang X, Shrimanker TV, Kolonin MG, Ueno NT. Body composition and breast cancer risk and treatment: mechanisms and impact. Breast Cancer Res Treat. 2021;186(2):273-283. [CrossRef] [Medline]
- Guigni BA, Callahan DM, Tourville TW, Miller MS, Fiske B, Voigt T, et al. Skeletal muscle atrophy and dysfunction in breast cancer patients: role for chemotherapy-derived oxidant stress. Am J Physiol Cell Physiol. 2018;315(5):C744-C756. [FREE Full text] [CrossRef] [Medline]
- Stout NL, Brown JC, Schwartz AL, Marshall TF, Campbell AM, Nekhlyudov L, et al. An exercise oncology clinical pathway: screening and referral for personalized interventions. Cancer. 2020;126(12):2750-2758. [FREE Full text] [CrossRef] [Medline]
- Patel AV, Friedenreich CM, Moore SC, Hayes SC, Silver JK, Campbell KL, et al. American College of Sports Medicine Roundtable Report on physical activity, sedentary behavior, and cancer prevention and control. Med Sci Sports Exerc. 2019;51(11):2391-2402. [FREE Full text] [CrossRef] [Medline]
- Murray J, Bennett H, Perry R, Bezak E, Davison K. How do practitioners prescribe exercise to patients with breast cancer? Professional perspectives on the key considerations for aerobic exercise in patients with breast cancer undergoing chemotherapy. J Sci Med Sport. 2023;26(12):650-658. [FREE Full text] [CrossRef] [Medline]
- Hayes SC, Newton RU, Spence RR, Galvão DA. The Exercise and Sports Science Australia position statement: exercise medicine in cancer management. J Sci Med Sport. 2019;22(11):1175-1199. [FREE Full text] [CrossRef] [Medline]
- Harris SR, Niesen-Vertommen SL. Challenging the myth of exercise-induced lymphedema following breast cancer: a series of case reports. J. Surg. Oncol. 2000;74(2):95-98. [CrossRef]
- Sweegers MG, Altenburg TM, Chinapaw MJ, Kalter J, Verdonck-de Leeuw IM, Courneya KS, et al. Which exercise prescriptions improve quality of life and physical function in patients with cancer during and following treatment? A systematic review and meta-analysis of randomised controlled trials. Br J Sports Med. 2018;52(8):505-513. [CrossRef] [Medline]
- Schmitz KH, Campbell AM, Stuiver MM, Pinto BM, Schwartz AL, Morris GS, et al. Exercise is medicine in oncology: engaging clinicians to help patients move through cancer. CA Cancer J Clin. 2019;69(6):468-484. [FREE Full text] [CrossRef] [Medline]
- Cormie P, Pumpa K, Galvão DA, Turner E, Spry N, Saunders C, et al. Is it safe and efficacious for women with lymphedema secondary to breast cancer to lift heavy weights during exercise: a randomised controlled trial. J Cancer Surviv. 2013;7(3):413-424. [CrossRef] [Medline]
- Watt FE. Musculoskeletal pain and menopause. Post Reprod Health. 2018;24(1):34-43. [CrossRef] [Medline]
- [Sample size calculator]. QuestionPro. URL: https://www.questionpro.com/es/calculadora-de-muestra.html [accessed 2024-09-30]
- [Hospital morbidity rates per 100,000 inhabitants according to main diagnosis, province, autonomous community and autonomous city of hospitalization]. Instituto Nacional de Estadística. URL: https://www.ine.es/jaxiT3/Datos.htm?tpx=66370 [accessed 2024-09-30]
- Guillaumes S, O'Callaghan CA. [Spanish version of the free OxMaR software for minimization and randomization of clinical studies]. Gac Sanit. 2019;33(4):395-397. [FREE Full text] [CrossRef] [Medline]
- Hudak PL, Amadio PC, Bombardier C, Beaton D, Cole D, Davis A, et al. Development of an upper extremity outcome measure: the DASH (disabilities of the arm, shoulder, and head). Am. J. Ind. Med. 1996;29(6):602-608. [CrossRef]
- Hervás MT, Navarro Collado MJN, Peiró S, Rodrigo Pérez JLR, López Matéu PL, Martínez Tello IM. [Spanish version of the DASH questionnaire. cross-cultural adaptation, reliability, validity and responsiveness]. Med Clin. 2006;127(12):441-447. [CrossRef] [Medline]
- Melzack R. The McGill Pain Questionnaire: Major properties and scoring methods. Pain. 1975:277-299. [CrossRef]
- Badia X, Muriel C, Gracia A, Núñez-Olarte JM, Perulero N, Gálvez R, et al. [Validation of the Spanish version of the brief pain inventory in patients with oncological pain]. Med Clin. 2003;120(2):52-59. [CrossRef] [Medline]
- Hasenoehrl T, Palma S, Ramazanova D, Kölbl H, Dorner TE, Keilani M, et al. Resistance exercise and breast cancer-related lymphedema—a systematic review update and meta-analysis. Support Care Cancer. 2020;28(8):3593-3603. [FREE Full text] [CrossRef] [Medline]
- Baechle TR, Earle RW. Essentials of Strength Training and Conditioning. Champaign, IL. Human Kinetics; 2008.
- Brown JC, Schmitz KH. Weight lifting and physical function among survivors of breast cancer: a post hoc analysis of a randomized controlled trial. J Clin Oncol. 2015;33(19):2184-2189. [FREE Full text] [CrossRef] [Medline]
- Hagstrom AD, Marshall PWM, Lonsdale C, Cheema BS, Fiatarone Singh MA, Green S. Resistance training improves fatigue and quality of life in previously sedentary breast cancer survivors: a randomised controlled trial. Eur J Cancer Care. 2016;25(5):784-794. [CrossRef] [Medline]
- Scott N, Fayers P, Aaronson N, Bottomley A, de GA, Groenvold M, et al. EORTC QLQ-C30 reference values. European Organisation for Research and Treatment of Cancer. 2008. URL: https://www.eortc.org/app/uploads/sites/2/2018/02/reference_values_manual2008.pdf [accessed 2024-09-30]
- Garrido LE, Pruja E, Marcos M, Tejedor M, Arias F. The EORTC Quality of Life Questionnaire QLQ-C30 (Version 2.0). Psychometric study with breast cancer patients. Clinical and Health Official College of Psychologists of Madrid. 2000;11(3):349. [CrossRef]
- World Medical Association. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194. [CrossRef] [Medline]
- Royal Decree 1591/2009, of October 16, 2009, which regulates medical devices. Agencia Estatal Boletín Oficial del Estado. 2009. URL: https://www.boe.es/buscar/act.php?id=BOE-A-2009-17606 [accessed 2025-03-04]
- Purtova N. The law of everything. Broad concept of personal data and future of EU data protection law. Law Innov Technol. 2018;10(1):40-81. [CrossRef]
- Montaño-Rojas LS, Romero-Pérez EM, Medina-Pérez C, Reguera-García MM, de Paz JA. Resistance training in breast cancer survivors: a systematic review of exercise programs. Int J Environ Res Public Health. 2020;17(18):6511. [FREE Full text] [CrossRef] [Medline]
- Cuthbert C, Twomey R, Bansal M, Rana B, Dhruva T, Livingston V, et al. The role of exercise for pain management in adults living with and beyond cancer: a systematic review and meta-analysis. Support Care Cancer. 2023;31(5):254. [FREE Full text] [CrossRef] [Medline]
- Omar MTA, Gwada RFM, Omar GSM, El-Sabagh RM, Mersal AAE. Low-intensity resistance training and compression garment in the management of breast cancer-related lymphedema: single-blinded randomized controlled trial. J Cancer Educ. 2020;35(6):1101-1110. [CrossRef] [Medline]
- Kong L, Gao R. Aerobic exercise combined with resistance exercise training improves cardiopulmonary function and blood lipid of patients with breast cancer: a systematic review and meta-analysis. Medicine. 2022;101(51):e32391. [FREE Full text] [CrossRef] [Medline]
- IBM SPSS statistics (version 28.0). IBM Corp. URL: https://www.ibm.com/support/pages/downloading-ibm-spss-statistics-28 [accessed 2021-05-25]
- Pallás JMA, Villa JJ. Clinical and epidemiological research methods. Hoboken, NJ. Wiley; 2019.
- Shen Q, Yang H. Impact of post-radiotherapy exercise on women with breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Rehabil Med. 2020;52(10):jrm00112. [FREE Full text] [CrossRef] [Medline]
- Zengin Alpozgen A, Razak Ozdincler A, Karanlik H, Yaman Agaoglu F, Narin AN. Effectiveness of pilates-based exercises on upper extremity disorders related with breast cancer treatment. Eur J Cancer Care. 2017;26(6):e12532. [CrossRef] [Medline]
- Loudon A, Barnett T, Piller N, Immink MA, Williams AD. Yoga management of breast cancer–related lymphoedema: a randomised controlled pilot-trial. BMC Complement Altern Med. 2014;14:214. [FREE Full text] [CrossRef] [Medline]
- Aydin M, Kose E, Odabas I, Meric Bingul B, Demirci D, Aydin Z. The effect of exercise on life quality and depression levels of breast cancer patients. Asian Pac J Cancer Prev. 2021;22(3):725-732. [CrossRef]
- Koevoets EW, Schagen SB, de Ruiter MB, Geerlings MI, Witlox L, van der Wall E, et al. Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study). Breast Cancer Res. 2022;24(1):36. [FREE Full text] [CrossRef] [Medline]
- Bruce J, Mazuquin B, Canaway A, Hossain A, Williamson E, Mistry P, et al. Exercise versus usual care after non-reconstructive breast cancer surgery (UK PROSPER): multicentre randomised controlled trial and economic evaluation. BMJ. 2021;375:e066542. [FREE Full text] [CrossRef] [Medline]
- Carayol M, Ninot G, Senesse P, Bleuse JP, Gourgou S, Sancho-Garnier H, et al. Short- and long-term impact of adapted physical activity and diet counseling during adjuvant breast cancer therapy: the "APAD1" randomized controlled trial. BMC Cancer. 2019;19(1):737. [FREE Full text] [CrossRef] [Medline]
- Vincent F, Deluche E, Bonis J, Leobon S, Antonini M, Laval C, et al. Home-based physical activity in patients with breast cancer: During and/or after chemotherapy? Impact on cardiorespiratory fitness. A 3-arm randomized controlled trial (APAC). Integr Cancer Ther. 2020;19:1534735420969818. [FREE Full text] [CrossRef] [Medline]
- Coletta AM, Agha NH, Baker FL, Niemiro GM, Mylabathula PL, Brewster AM, et al. The impact of high-intensity interval exercise training on NK-cell function and circulating myokines for breast cancer prevention among women at high risk for breast cancer. Breast Cancer Res Treat. 2021;187(2):407-416. [FREE Full text] [CrossRef] [Medline]
- Khosravi N, Eskandari Z, Farajivafa V, Hanson ED, Agha-Alinejad H, Abdollah-Pour A, et al. Effect of 6 months of aerobic training on adipokines as breast cancer risk factors in postmenopausal women: a randomized controlled trial. J Cancer Res Ther. 2018;14(6):1336-1340. [FREE Full text] [CrossRef] [Medline]
Abbreviations
| COSA: Clinical Oncology Society of Australia |
| EORTC: European Organization for Research and Treatment of Cancer |
| MR: maximum repetition |
| WHO: World Health Organization |
Edited by A Schwartz; submitted 05.07.24; peer-reviewed by C Fox-Harding; comments to author 27.08.24; revised version received 30.09.24; accepted 10.01.25; published 12.03.25.
Copyright©Jennifer García-Molina, Olalla Saiz-Vázquez, Montserrat Santamaría-Vázquez, Juan Hilario Ortiz-Huerta. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.03.2025.
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