Abstract
Women with breast cancer (BC) experience multiple symptoms related to neoadjuvant chemotherapy (NAC) treatment that impair their functioning and quality of life (QoL). This study aimed to explore the effect of high-intensity aerobic interval training (HIIT) on quality of life and NAC side effects in women with BC. Methods: 56 patients (48.56 (7.84) years, range 35-64 years) diagnosed locally advanced (stage II-III) ER + BC receiving doxorubicin/cyclophosphamide-based NAC were randomly assigned to the HIIT group and a control group (CG) for 6 months. The HIIT group performed 2 to 3 HIIT sessions per week according to the study protocol (4 × 4 minutes at 85%-95% peak heart rate (HR)). The CG followed the standard of care instructions by the oncologists. To assess the QoL participants completed the EORTC QLQ-C30 with the additional BC module of QLQ BR-23. Weekly self-reports on NAC side effects were collected through online survey. Results: Study data were analyzed for 37 participants (nHIIT = 17, nCON = 20) who reported at least 14 (60%) weeks. HIIT was effective to reduce BC symptom scale outcomes (ES = 0.113, P = .048), and alleviate systemic therapy side effects (ES = 0.154, P = .020) and cancer related symptoms (ES = 0.124, P = .038). The most common side effect participants experienced at least 1 to 4 days/week was pain (average 50.9% and 56.8% for HIIT and CG, respectively), followed by sleep disturbances (average 50.9% and 49.9%, respectively). About 31% in both groups experienced sleep disturbances 5 to 7 days/week. The NAC induced physical, social and fatigue side effects had significantly lower incidence in HIIT group, while psychological side effects were significantly more common in training group. Conclusions: HIIT is an effective physical exercise program to maintain higher quality of life and help to reduce some of NAC induced side effects for women with BC.
Introduction
Chemotherapy constitutes a fundamental component in the treatment for breast cancer (BC). However, it is associated with multiple adverse effects that encompass physical, emotional and social aspects of patients’ quality of life. 1 Along with the detrimental effects of cancer therapies, other patient-related factors, including sedentary lifestyle behaviors and aging constitute additional aspects affecting both physical and mental well-being. 2 The prolonged periods of inactivity can lead to physical deconditioning, resulting in fatigue, muscle atrophy, and diminished physical capabilities, thereby provoke the decline in quality of life. Moreover, the cancer treatment toxicity symptoms (eg, dyspnea, fatigue, pain) can last for months and years after the treatment completed. 3
For patients with locally advanced BC the treatment includes neoadjuvant chemotherapy (NACT) to reduce the extent of surgical resection and facilitate breast-conserving surgery. 4 The modifiable risk factors such as cardiorespiratory fitness, body weight, and health behaviors should be addressed during early phase of BC treatment to reduce severity of the NACT side effects. Currently it is common for international and national oncology organizations to promote physical activity guidelines for cancer patients, incorporating aerobic and resistance exercise into standard care protocols during and post-treatment. 5 Physical activity among cancer patients has demonstrated effectiveness in enhancing quality of life, functional capacity, cardiorespiratory fitness, and mitigating symptom burden, such as fatigue, while also reducing systemic inflammation.6 -8
Despite the increasing evidence of the significance of physical activities during cancer treatment, researchers report difficulties in retaining cancer patients within physical activity interventions due to time restrictions (work, family duties), financial difficulties, adverse treatment effects, and transportation problems. 9 Notably, with recent developments in mobile technology and its widespread accessibility, there is potential for more frequent monitoring and guidance of individuals engaging in exercise. 10 This could provide affordable methods to encourage patients to maintain the intended adherence level by managing the intervention process on their own. Importantly, smartphone applications and related alerts can boost compliance with self-directed exercise routines. Therefore, these apps might improve the outcomes of self-managed home-based exercise and serve as a practical substitute for supervised exercise that requires significant time and resources. 11 Nevertheless, current findings on the effectiveness of exercise rehabilitation guided by apps remain inconclusive. However, it remains elusive whether high intensity aerobic interval training could improve quality of life (QoL) during NACT for BC patients.
Over the preceding 2 decades, the growing body of research studies have demonstrated physiological benefits of high intensity interval training (HIIT) programs as a recognized and feasible interventions for BC patients during and following the cancer treatment.6,12 However, knowing the complex impact of cancer and its treatment on patients’ physical, social and emotional health, oncologists and healthcare practitioners are concerned about prescribing high-intensity exercise for BC patients. For example, a recent umbrella review of the 7 systematic reviews with meta-analyses demonstrated that, when used alongside standard cancer therapies, HIIT is an effective intervention for mitigating cancer-related fatigue and enhancing quality of life. Additionally, HIIT exhibits a high adherence rate among participants. The application of HIIT in individuals with cancer or cancer survivors has been shown to be safe, with minimal or no adverse effects reported. 12 Only one review has been found on BC treatment with 18 articles from 10 studies reporting that HIIT was more effective than standard care to improve VO2 peak and muscle strength outcomes, mitigate fatigue and emotional disturbances in BC patients. The HIIT intervention duration in studies ranged from 6 to 16 weeks, with an average frequency of 2.7 HIIT sessions per week. Authors noted that further research is needed to elucidate the effect of HIIT on therapy induced adverse symptoms in women in BC. 6 Nonetheless, the optimal dosage, length and intensity of exercise program during treatment remains unclear. This study investigated the effect of HIIT intervention on QoL and incidence of side effects during prolonged NACT cancer treatment (6 months). In addition, the weekly patients’ self-reports of NACT side effects were obtained to monitor incidence and prevalence of NACT induced adverse symptoms. It was hypothesized that HIIT intervention will have a significant effect on quality of life and that the intervention group will present lower incidence rate of NACT related side effect compared to the standard of care group (CG).
Methods
Fifty-six patients (48.56 years, SD = 7.84) with newly diagnosed locally advanced (stage II-III) BC who required neoadjuvant chemotherapy (NACT) were recruited from the Breast Cancer Clinic, Riga East University Hospital (Latvia), by medical oncologists, with following inclusion criteria: age from 36 to 65 years; BMI > 18, ≤30; BC stage II to III; familiar with the use of smartphone apps; able to travel to the research facilities for testing. The patients received NACT according to the European Society for Medical Oncology and the National Comprehensive Cancer Network guidelines (doxorubicin, cyclophosphamide—docetaxel and/ or doxorubicin, cyclophosphamide—paclitaxel regime and/or trastuzumab/pertuzumab “Phesgo”). Patients were excluded if they participated in other research providing physical activity, or had musculoskeletal, neurological, cardiovascular, endocrine, and respiratory conditions that contraindicated submaximal aerobic loads. Also, the following discontinuation criteria were applied: change of planned treatment during NCT; loss of follow-up; failed to perform any physical assessments.
From 56 initially recruited and randomized participants, 37 were included in final data analyses (Figure 1). The most frequent reasons for participants’ withdrawal from the study were unexplained personal reasons (eg, did not respond to phone calls or email messages) and due to severe NACT side effects. There were no significant differences at baseline between both groups regarding participant characteristic data (Table 1). Also, the participant characteristics between those who withdrew and those who completed the study did not present significant differences.
Study diagram.
Participant Characteristics.
Data were collected between January 2022 and December, 2023. Patient written and informed consent was obtained during the first meeting with the research staff. The study ethical approval was obtained from the LASE ethical committee (Nr. 1/2021/28/05) and the Scientific Department of Riga East University Hospital (REUH) (reg. nr. ZD/08-06/01-21/179), and study was registered at ClinicalTrials.gov. (NCT06522971).
The recruited patients were randomly allocated to either HIIT or the control group (CG) at a ration 1:1 before the first assessment that was scheduled before the first NACT session. To ensure impartiality in allocation, the Breast Cancer Clinic at the REUH performed the randomization by using the table of random numbers. Allocation concealment was done by using sequentially numbered, opaque, and sealed envelopes that were opened by independent research staff member not involved in this study. Research personnel who applied the assessment and monitored HIIT intervention were not blinded. On other hand, other co-investigators involved in data analyses (blood and tumor samples) were blinded to the intervention allocation. This publication addressed the part of the study data related to assessment of quality of life and incidence rate of NACT related side effects.
Quality of Life Assessment
Quality of life (QoL) was measured by the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30), a 30-item questionnaire (version 3.0), and an additional Breast cancer module (QLQ-BR23). The EORTC QLQ-C30 is the commonly used questionnaire for assessing QoL specific for cancer patients. 13 This questionnaire includes thirty items covering 5e functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning), 3 symptom scales, a global health status/QoL scale, and 6 single items. Each multi-item scale contains a distinct set of items, with no overlap between scales. Additionally, the QLQ-BR23 module includes 23 questions addressing disease symptoms, treatment side effects (surgery, chemotherapy, radiotherapy, and hormonal treatment), body image, sexual functioning, and future perspectives. All scales and single-item measures yield scores ranging from 0 to 100. A high score on a functional scale indicates superior or healthy functioning and a high score on the global health status/QoL scale indicates a high quality of life. Conversely, a high score on a symptom scale or item indicates a heightened level of health complaints and/or presence of treatment side effects. 13 Both questionnaires have undergone validation and cross-cultural testing across diverse cancer populations, including Latvia.14 -16 Participants completed questionnaires online. Participants completed surveys independently in a quiet environment with no restriction in time. Also, participants were assigned codes to maintain anonymity throughout the study.
All participants of the intervention group were prescribed 6 months HIIT walking program including 2 to 3 sessions per week (64 sessions in total). The intervention was implemented during NACT period (overall, 8 NACT during the 6 months). Because of the broad geographical range of participants’ home locations, they had free choice where to do intervention sessions (eg, on treadmills in the fitness centers, on trails, or in the stadium outside). Each participant received one to three 30 minutes individual training sessions on the treadmill at the beginning of the intervention. Training sessions were supervised by the functional specialist/ researcher of this study (physiotherapist with more than 10 years of professional experience). During the first training session (organized before the first NACT) a participant received the equipment (Polar H10 heart rate monitor) and was instructed on how to use it with Polar Flow application (https://flow.polar.com/) during the HIIT activity on the treadmill. If patients expressed need for more supervised sessions, they could sign up for the 2 more training sessions. The second training session was scheduled after the first NACT (within 2-5 days). Each participant received assistance on preparing the Polar HR device, phone application, and was partially assisted during the HIIT session. The third training session was similar to the second, while assistance was provided only by request of the participant. Every HIIT session started with a 6-minute warm-up at a self-selected walking speed on the treadmill (incline ≥ 2%) and progressing to moderate intensity (approximately 60%-70% HRmax) corresponding to 4 on Modified Borg’s scale (moderate self-perceived exertion) by the end of the warm-up phase. After the warm-up the main part of 4 min × 4 min walking intervals at 85% to 95% HRmax (7-8 on Modified Borg’s scale) was implemented. Each 4-minute interval was combined with a 3 minute period of active recovery at 55% to 70% of HRmax. In total the session lasted 34 minutes. The participant sent the physiotherapist screenshots of the training output from Polar Flow app after each session. The adherence measures were calculated as the percentage of 64 sessions (100%) completed by each participant. Adherence level was acceptable if completed 30 (62%) training sessions, as described in previous studies.17,18 The individual patient’s training charts and attendance were tallied as number of attended HIIT sessions over number of scheduled HIIT sessions. During the NACT treatment period the HIIT group patients were encouraged to continue training. If the patient indicated severe NACT related side effects in weekly health symptom reports, she was contacted by the functional specialist to discuss the need for modifications in training protocol, for example, reducing intensity to 80%-75% of HRmax. The initial training regime was resumed as side-effects decreased.
Weekly Health Monitoring
Patients were asked to answer 7 questions weekly through electronic survey form on phone or computer for a total of 24 weeks (6 months). The 6 questions included common chemotherapy side effects selected as meaningful from the patient perspective18,19: (1) physical functioning (difficulty performing any daily physical activities—standing for more than 30 minutes, lifting and carrying an object etc.); (2) psychological functioning (feel emotional exhaustion—sadness, depressed mood, nervousness etc.,); (3) pain (pain in legs, stomach, neck, bone pain, muscle pain etc.); (4) fatigue (feeling tired at rest, difficult to concentrate, difficult to make a decision etc.); (5) social functioning (do not want to communicate with family members, meet friends, participate in social activities etc.); and (6) sleep quality (difficulty falling asleep, restless sleep, inability to go back to sleep after waking up at night etc.). For all side effects, the duration of symptom experience was indicated (every day, 5-6 days, 3-4 days, 1-2 days, none of the days). Additionally, the 5 specific side effects (eg, nausea, vomiting, constipation, feeling of numbness in legs or arms, rash/ulcers on the skin) were listed at the end of the survey. Participants were asked to report any specific side effect experienced at least once during the last 7 days. A reminder was sent if the participant did not submit a report for the previous 7 days. The questionnaire was developed through a comprehensive review of the literature and consultation with clinical staff at the Breast Cancer Clinic, REUH, to identify NACT-related side effects. Development involved pilot testing with 5 women after NACT, followed by refinement. As minimal adjustments were needed after pilot testing, re-piloting was deemed unnecessary. Completing the questionnaire typically took participants 3 to 5 minutes.
Analyses
Baseline participant characteristics were summarized using descriptive statistics. Quality of life outcome data were presented as mean (SD). For group comparisons of baseline participant characteristics, independent sample t-tests were used. To compare the means of pre and post-intervention within groups the paired t-test was used, with significance set at P < .05 A repeated measures ANCOVA model was conducted with the intervention group and time (baseline/post-intervention) as factors. The effect size (ES) was quantified using partial eta squared (ηp 2 ). The overall frequency of side effects was determined by calculation the number and proportion of participants’ weeks when the side effect was reported during the intervention period. Prevalence was calculated as the proportion of days per week in which each side effect was reported. The incidence rate of self-reported side effects was calculated by dividing the number of individuals who experienced the specified side effect by the total person-weeks during the intervention. This approach aligns with the standard practice of reporting side effects in the clinical trial literature. The partial eta squared (ηp 2 ) measures were used to measure the effect size (ES). According to Cohen 20 the effects were defined as small (ηp 2 = 0.01), medium (ηp 2 = 0.06), and large (ηp 2 = 0.14). The 2-tailed P < .05 was considered significant.
Results
The HIIT presented 79 ± 14% adherence rate during intervention (51/64 sessions). No adverse events were reported during assessments or intervention sessions. Of 56 patients initially included in the study, 37 complied with the requirements to be included in data analyses of this study. Table 2 presents within and between group results of QoL before and after the study. Both groups, HIIT and CG, after intervention demonstrated significant reduction in average scores of EORTC-30 Physical Functioning (P = .041, P = .033, respectively) and Social Scale scores (P = .013, P = .025, respectively). The CG significantly decreased average score of Role Functioning scale (P = .021). Symptom Scale scores did not present significant change from pre to post intervention within both groups, while according to the analyses of covariance there was significantly less BC symptomatology reported after the study for HIIT group compared to CG (P = .048, ES = 0.113).
Changes in Quality-of-Life Domains of HIIT and CG Groups.
The data in bold are to present those that are significant.
Abbreviations: CG, control group; HIIT, high intensity interval training.
P < .05 indicates significant changes between groups.
Indicates significant effect size.
P < .05 compared to baseline.
Regarding EORTC -QLQ-BR23 both groups, HIIT and CG, after intervention reported significant reduction in average scores of Body Image (P = .002, P = .003, respectively), while significant increase in Symptom Scale (BR23) (P = .049, P = .022, respectively). Also, the average scores of the Symptom Scale (BR23) showed significant differences between both study groups (P = .038, ES = 0.124). After intervention the HIIT group demonstrated significantly higher average scores of Sexual Functioning (P = .040), while significant increase in average Systemic therapy side effects (P = .006) and decrease in Breast
Symptom Scale scores (P = .048) scores comparing to the pre-intervention. The average scores of Systemic therapy side effects showed significant differences between HIIT and CG after intervention (P = .020, ES = 0.154).
Table 3 presents the frequency and incidence rate of each side effect during the data collection. All participants reported that they at least once experienced the side effects listed in the survey during the study period. For HIIT group the sleep disturbances were most frequently indicated side effects (21.3%), while for CG it was tiredness (43.0%). The self-reports on pain and sleep disturbances were not statistically different between participants of both study groups. The physical symptoms, tiredness and social function problems were significantly more frequently indicated in CG (P = .016, P = .015, and P = .043, respectively), while psychological complaints were more frequent in the HIIT group (P = .023). The incidence rates for sleep disturbances and pain were highest in both groups. In the HIIT group the sleep problems had the overall highest incidence (0.84 per person per week), followed by pain (0.82 per person per week). In CG the reports of pain had the overall highest incidence (0.85 per person per week), followed by sleep disturbances (0.80 per person per week).
Frequency and Incidence Rate of Self-Reported Side Effects.
The data in bold are to present those that are significant.
P < .05 indicates significant changes between groups.
As part of weekly health monitoring, all participants were asked to report on 5 additional specific side effects experienced during the NACT period (Table 4). For both groups, HIIT and CG, constipation was the most common side effect (26.4% and 24.8%, respectively). The feeling of numbness in legs and arms was the next most frequently reported side effect (26.7% and 19.7%, respectively). Interestingly there was a larger proportion of participants in CG who did not experience any of the specific side effects (21.4%) compared to the HIIT group (14.8%).
Frequency and Incidence Rate of Specific Self-Reported Side Effects.
The prevalence of side effects was calculated as the proportion of patients reporting number of days per week they experienced the side effects. In addition, the data on proportion of weeks when none of side effects was presented also was calculated. In HIIT and CG sleep disturbances overall were the most prevalent side effects (5-7 weekdays 31.7% and 31.3%, respectively and 1-4 weekdays 50.9% and 49.4%, respectively). The pain-related side effects had overall highest prevalence reported by participants at least once per week (1-4 weekdays) in HIIT group and CG (53.7%, 58.0%, respectively). More than 50% of HIIT group participants did not experience any physical and social functioning side effects (56.9%, 57.8%, respectively). See Table 5 for details.
Prevalence (Proportion) of Self-Reported Side Effects.
Discussion
The aim of this study was to examine the impact of HIIT on the quality of life and the occurrence, frequency, and prevalence of self-reported non-adherence-related adverse effects during a 6-month treatment period in 37 women diagnosed with BC. This research represents a pioneering effort in Latvia, employing an online weekly monitoring tool to collect data of self-reported NACT induced side effects, thereby highlighting the effects of HIIT programs during the prolonged period of chemotherapy. The results of this investigation have the potential to contribute deeper understanding of the impact of physical activity on different parameters of quality of life in the context of BC treatment process. In line with previous studies using HIIT during BC treatment, all participants were women with stage I-III BC, without metastases, recurrence, or secondary cancers at the time of enrollment. 6
In this study the EORTC-QLQ-C30 data outcomes demonstrated that HIIT had beneficial effects on reducing BC related symptoms (Symptom Scale). It should be noted that at the first QoL assessment that was within a week after diagnosis some participants of the CG indicated multiple disease related symptoms, creating large variability in the data compared to the HIIT group (SD = 34.87 and SD = 13.57, respectively). Previous studies showed that cancer patients, including BC patients, face uncertain prognoses, and existential threats linked to mortality during early post-diagnostic period, which can be highly distressing and adversely impact quality of life. Psychological issues, such as anxiety and depressive symptoms were related to perceptions of illness ambiguity and to an intolerance of uncertainty.21,22 Furthermore, the EORTC-QLQ-BC23 outcomes demonstrated significant effect of the HIIT on Systemic Therapy and Symptom Scale results. There are a limited number of studies published reporting outcomes of HIIT effects on multiple factors of QoL. Moreover, the use of different survey instruments across studies makes challenging to compare outcomes from this study with others. For example, Mijwel et al 17 compared the effect of resistance HIIT (RT-HIIT) and aerobic HIIT (AT-HIIT) and usual care (UC) on health-related quality of life in BC patients during chemotherapy. Our study findings were in line with Mijwel et al in reporting that the level of negative changes in physical function and pain scores was lower in both training groups compared to the UC. Also, consistent with our results, Mijwel et al found that significant decline was observed in Role Functioning for the UC/control group. The present study did not observe significant changes in Emotional Functioning for both groups, however, the aerobic HIIT interventions have been proved superior to other training modes (eg, resistance, moderate intensity aerobic training) in improving Emotional Functioning of BC patients23,24 and other patient groups, for example, in the elderly.24,25 Also, the previous findings suggest that HIIT can improve emotional well-being with supervised exercise interventions in BC patients during and after the treatment.26,27 In our study results might differ because patients independently from each other participated in the HIIT program in their home environment with remote monitoring of training sessions through the Polar Flow app. Also, the reduced effect sizes in this study compared to other studies (ES from 0.113 to 0.154) might be explained by different data analyses methods across studies and the free-living training program methodology. The EORTC-QLQ-BR23 Body Image scores significantly decreased for both groups with no significant effect after the intervention. These findings align with prior research, demonstrating that patients with BC undergoing chemotherapy exhibit heightened sensitivity toward their body image, potentially leading to significant alterations in their perception of self-image.28,29 In addition, pre-habilitation has been suggested between cancer diagnosis and the initiation of acute treatment aiming to enhance the patient’s health and mitigate the incidence and severity of present and future impairments. Implementing pre-habilitation prior to initiating systemic therapies has contributed to management of treatment-associated body changes (eg, weight gain) while enhancing both objective and patient-reported outcomes (eg, sexual health). 30 Interestingly, that HIIT group presented significantly higher Sexual Functioning scores after intervention compared to CG, which is opposite to other study outcomes reporting problems with sexual interest or activity throughout chemotherapy.27,31 Some studies reported beneficial effects of sexual education and/or counseling interventions during BC therapy in patients with BC.32,33 In current study we did not collect information on whether participants were attending activities or counseling with health professionals on sexual health. Nonetheless, this topic often remains unaddressed by both healthcare providers and patients, owing to a variety of subjective and socio-cultural factors.
To our knowledge no studies have reported weekly data outcomes on NACT related side effects in BC patients (stage II-III) during longitudinal HIIT intervention (6 months). Previous studies have described incidence of common chemotherapy side effects collected on monthly bases in different types of cancer patients (BC, colorectal cancer, lung cancer, gastric, periampullary) using interviews with patients.19,34 A recent review described data outcomes of 20 studies on the effect of participating in an exercise intervention on the duration and frequency of hospital admission during cancer treatment. 35 Therefore, it was challenging to compare the effect of the individually prescribed HIIT intervention program on frequency and incidence rates of NACT side effects obtained during current study with other published studies in the literature.
In the current study all participants experienced at least one side effect during NACT with sleep disturbances being the most prevalent in both groups (>30% 5-7 days/week, >0.8 per total person-weeks). In the literature sleep difficulties are reported by 30%-60% of cancer patients undergoing chemotherapy. This might subsequently have significant impact on QOL7,8 and negatively affect the treatment. 36 Previous research studies reported that the increase of sleep disturbances and concurrent symptom presentation are predisposed by multiple factors, for example, hormonal changes, treatment modalities, environmental factors, lifestyle habits, and cytokine changes are interrelated with the diagnosis and treatment. 37 Sleep problems during chemotherapy often are explored in relation to other specific side effects which have been reported to closely associate with reduced sleep quality. For example, fatigue has been listed as the most common cancer treatment related side effect 2 demonstrating high frequency and incidence rates (≥78%).19,34 While the current study reported overall lower incidence rates of fatigue compared to previously published data, the CG reported significantly higher average rates than HIIT group. These findings were in line with outcomes from other studies implementing physical exercise interventions showing that fatigue significantly decreased in the intervention group relative to the control group, for example, after the 18-week aerobic and resistance exercise program, 38 8-week HIIT intervention, 26 and 16 weeks of resistance and aerobic HIIT. 17 However, in comparison to our investigation, previous studies implemented supervised training sessions, shorter intervention periods, different durations of HIIT, various chemotherapy protocols, and diverse exercise methodologies. As hypothesized by authors, longer exercise interventions might provide multiple significant benefits in patient reported outcomes during BC chemotherapy treatment. 26
The present study showed significantly lower incidence rates for the HIIT group compared to the CG on social, physical, and fatigue side effects, while psychological health problems were more common for HIIT group, presenting high daily (5-7 days/week) prevalence. Patients undergoing chemotherapy often experience physical discomfort, for example, peripheral neuropathy characterized by numbness, paresthesia, and pain. 39 These changes not only cause discomfort but also have detrimental effects on their quality of life, particularly impacting their psychological well-being. 40 In this study the HIIT group more frequently reported symptoms of numbness in legs and arms, which might be associated with lower psychological wellbeing. In addition, as the intervention was implemented independently where participants were free to choose the environmental and social contexts for training sessions (eg, in the fitness gym, or in nature, with family members, or alone), we can relate observed differences in social function scores to the familiar environment for patients where other people (eg, family members, friends, colleagues) could play meaningful roles in providing social support and encouragement throughout the treatment period. Anecdotal notes from the study confirmed that participants often were accompanied by a close friend/colleague or family member to the assessment sessions and shared the positive experience of feeling supported and being motivated by people around in home or work environment.
The strength of this study includes randomized control design, comprehensive measures of the QoL and weekly self-reports on NACT-related side effects during prolonged (6 months) treatment. The HIIT protocol was prescribed to each patient with individualized intensity (heart rate zones) for 4 min × 4 min walking intervals. The Polar application used for reporting on each training session and communicating with the research team helped to achieve compliance with the prescribed HIIT intervention. Compared to previous similar studies implementing HIIT during BC treatment, this study differed in the timing (before the start of NACT) and methodology of the intervention (free-living training program). In previous studies the HIIT was mainly provided at the hospital during17,18 or after chemotherapy.24,41 Mostly interventions were supervised by health care professionals ensuring the high adherence. The present study is, to our knowledge, the first to explore the effect of the 6 months free-living HIIT intervention program on the QoL and incidence rate of NACT related side effects.
Limitations and Future Implications
The study sample was limited since there was large variability in social and economic situation of participants in both groups. Also, this study did not differentiate between participants attending or not participating in additional educational and counseling programs (eg, psychological therapy groups) that might affect the QoL and the incidence level of weekly self-reported NACT relate side effects. For example, some symptoms of psychological and social characteristics may have been mistaken for side effects of chemotherapy. In addition, results should be viewed with caution because the dropout rate was high in both study groups. However, in line with previous studies, 6 better treatment outcomes and fewer NACT-related side effects were found to be associated with study retention. Per-protocol analysis (evaluating the effect of treatment) was used in this study, including only data from patients who followed the HIIT intervention protocol. In future studies intention-to-treat analysis, which is the most frequently used approach in randomized clinical trials, should be used parallel to the per-protocol strategy.
Another limitation lies in the uncertainty regarding clinical treatment of some of the reported side effects. For example, some patients received immunotherapy or were prescribed additional medicaments during NACT. The information on additional treatment to mitigate NACT side effects could have led to more detailed analyses of data outcomes.
Additional limitations were the different levels of patient proficiency with the Polar Flow app and technical challenges in reporting the visual training data. This impeded the accurate evaluation of exercise intensity solely via self-reported ratings of perceived exertion (RPE). Incorporating additional social incentives or regular group interactions could have potentially strengthened adherence to training protocols and facilitated peer support, fostering social support and reducing isolation from other participants during treatment. This, in turn, might improve adherence and contribute to emotional wellbeing.
Conclusions
This study contributes to the existing literature by providing an estimation of the effect of HIIT intervention on the quality of life and incidence of side effects experienced by BC patients during NACT. The 6 months HIIT was effective in maintaining higher QoL in Physical Functioning, reducing BC symptoms and mitigating systemic therapy-related side effects. The HIIT significantly reduced physical, social health-related and fatigue side effects. Findings from this study provide significant evidence on the advantages of HIIT intervention for health outcomes in BC patients undergoing NACT. This allows healthcare professionals in oncology to recommend integrating HIIT into targeted treatment for patients with BC.
Footnotes
Authors’ Contributions
AK, KE, AL, AIL designed research, GFJ, MČ, and RC performed research and participated in the analysis and interpretation of the results, AK performed data analysis and statistical analyses. AK, RC, and MC wrote the manuscript, AL, GFJ, and ALl edited the manuscript. KE organized the recruitment of patients. All authors have read and approved the manuscript.
Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by EEA and Norway Grants under project Nr. EEZ/BPP/VIAA/2021/2 (CancerBeat).
