Abstract
Chemotherapy used to treat breast cancer (BC) in young women often results in significant side effects, among others myelotoxicity, nausea, neurotoxicity, ataxia, and fatigue. These negative effects can be offset by physical activity employed concurrently with the treatment. One of the training modalities – high-intensity interval training (HIIT) – has been the subject of many studies showing significant health benefits, with the advantage of being time-efficient. The aim of this study was to investigate whether HIIT can be successfully employed for young BC patients undergoing chemotherapy. Forty young (18–40 years old) BC patients scheduled for chemotherapy were randomized to undergo supervised HIIT concurrently with chemotherapy or instructed to perform World Health Organization-recommended volume of daily physical activity (control group). Measurements included retention, adherence to training, and body composition parameters (BMI, muscle mass, fat mass, handgrip strength on affected and unaffected side) measured before and after therapy. HIIT scheduled concurrently with chemotherapy was a feasible approach for young BC patients (retention: 94.74%, adherence: 100%). Employment of HIIT also resulted in higher handgrip strength compared to no supervised training (1.2 kg between-group difference). This study shows that HIIT introduced and conducted along the chemotherapy is feasible for young BC patients. This approach can offset the negative effects of chemotherapy on physical fitness.
Trial registration
The study was registered in the clinicaltrials.gov registry (#NCT06190600) on 05/01/2024, retrospectively registered.
Introduction
In 2020 as per the Global Cancer Observatory (GLOBOCAN) database, 779,931 new cancer cases were diagnosed in the population of young women aged 20–39, 32% of which were breast cancer cases1. Although breast cancer-specific survival has increased in recent years, new research consistently shows that women younger than 40 experience significantly worse outcomes2. This group is more likely to present with higher-grade tumours and more aggressive subtypes than older patients are, which calls for a different therapeutic approach.
Young patients are more often diagnosed with triple-negative breast cancer (TNBC) or HER2-positive breast cancer, both of which are associated with worse outcomes3. The standard treatment of choice for these subtypes comprises chemotherapy administered to shrink the tumour before surgical excision (neoadjuvant chemotherapy). The side effects of chemotherapy (doxorubicin, paclitaxel, docetaxel, all used in breast cancer treatment) include neurotoxicity, which can result in paraesthesia, ataxia, and paralysis4. Additionally, chemotherapy can impair the function of the cardiovascular-skeletal muscle axis5 and cause prolonged fatigue6. The often observed side effects of chemotherapy can severely lower a patient’s quality of life.
The significant increase in fatigue and muscle strength loss following chemotherapy7 underscore the need for early implementation of physical therapy. While health-related quality of life declines due to chemotherapy, physical exercise significantly mitigates this effect8. For this reason, the choice of exercise plan can be crucial, as the lack of time for exercise is one of the main reasons for its discontinuation. To ensure adherence to the protocol, training should be safe and feasible throughout the treatment. In recent years research, predominantly on cardiovascular diseases, has revealed the benefits of higher-intensity training conducted in shorter spurts – high-intensity interval training (HIIT). This approach yields results similar to those of continuous moderate-intensity training regarding cardiovascular health with the benefit of being more time-efficient9. Additionally, studies suggest a positive effect on body composition and muscle strength10 which is particularly desirable for patients suffering from chemotherapy-induced fatigue. The OptiTrain trial showed that HIIT combined with resistance training can significantly improve muscle strength in breast cancer patients undergoing chemotherapy11 and help preserve their cardiovascular health12. Other studies have demonstrated its safety and positive effects in breast cancer survivors13.
The aim of this study was to investigate whether HIIT can be successfully implemented for young BC patients undergoing chemotherapy. While HIIT is physically demanding and may pose a challenge for chemotherapy-fatigued patients, on the basis of the current state of knowledge, we hypothesize that its implementation is feasible and can improve physical fitness (body composition and handgrip strength) in patients undergoing chemotherapy. In this study, we evaluated the feasibility of HIIT for young breast cancer patients undergoing chemotherapy and as a secondary aim assessed its impact on body composition and handgrip strength.
Materials and methods
Trial design
This randomized trial was designed as an open-label, parallel, quantitative study to identify the superiority of the intervention. Patients receiving neoadjuvant chemotherapy were randomly allocated at a 1:1 ratio to two groups: high-intensity interval training (HIIT) and the control. The participants were assessed at two time points: baseline (within a week before starting treatment) and at the end of treatment (within a week after finishing treatment).
Recruitment of participants
First, at the medical consultation of the senior staff, the basic inclusion criteria of the study were evaluated (histopathological cancer type and patient age). Patients who met these criteria were referred to an oncologist (principal investigator) who approached the patients regarding the participation in the study, and conducted further eligibility assessment. As part of this assessment, the oncologist requested echocardiography and blood tests to be performed.
Participants
A total of 40 patients diagnosed with breast cancer were recruited for the study at the Greater Poland Cancer Centre, Poznan, Poland. Participants were recruited and randomised between 21st January 2019 and 23rd June 2020, and treated and assessed between January 2019 and December 2020. The study ended when the last participant underwent post-treatment assessment.
First, during the medical consultation of the senior staff, the histopathological cancer type and patient age were assessed, and only the patients who met these preliminary criteria were referred to the PI for the actual eligibility assessment. The inclusion criteria for enrolment were as follows: women, aged 18–40, with specific breast cancer diagnoses confirmed by histopathology, and with a performance status described on the Eastern Cooperative Oncology Group (ECOG) scale as 0–1. The ECOG scale 0 describes patients who are “Fully active, able to carry on all pre-disease performance without restriction”, and 1 describes patients “Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work”14. The study included patients with TNBC or HER2-positive breast cancer when the tumour size was ≥ 2 cm and/or with positive axillary lymph nodes or with luminal breast cancer > 3 cm in size and/or positive axillary lymph nodes. All the patients were eligible for neoadjuvant chemotherapy (doxorubicin, cyclophosphamide, followed by paclitaxel, in the case of HER-2 positive cancer trastuzumab, pertuzumab). The qualified participants had to have a > 50% left ventricular ejection fraction (LVEF) and positive blood results to estimate the function of the bone marrow, liver, and kidneys (leukocytes ≥ 3 × 109/l, neutrophils ≥ 1.5 × 109/l, haemoglobin ≥ 9 mg/dl (5.59 mmol/l), blood platelets ≥ 100 × 109/l, AST/ALT ≤ 3 x upper limit of normal (ULN), bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 ULN). The participants had to meet the European Society For Medical Oncology (ESMO) criteria for planned systemic treatment: doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, and pertuzumab15.
The exclusion criteria were a diagnosis of breast cancer with characteristics other than those listed in the inclusion criteria, a performance status described on the ECOG scale as ≥ 2, and a diagnosis of cancers other than cancer of the breast (excluding in situ melanoma, in situ ovarian cancer, basal cell carcinoma, and squamous cell carcinoma without metastases) within the previous 5 years. All the participants were required to use barrier contraceptives during treatment and six months after finishing treatment. Participants who were pregnant or were breastfeeding were excluded from the study. Patients with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection, after organ transplantation and those with autoimmune diseases requiring immunosuppressive treatment were also excluded. Additionally, the physician assessed whether each participant had any diseases impairing movement or other diseases that would prevent participants from undergoing treatment safely, and those participants were also excluded from the study.
Subject eligibility was determined by an oncologist who, at the time of the decision, was unaware of the group to which the subject would be allocated. Participants were randomized at a 1:1 ratio to the HIIT group and to the control group with stratification on the basis of TNM classification and the biological subtype of breast cancer. The eligible participants were randomly allocated by a physiotherapist via an Interactive Web Response Systems (IWRS) on the basis of Food and Drug Administration (FDA) guidelines (Title 21 CFR Part 11). Nineteen participants were allocated to the HIIT group, and 21 participants were allocated to the control group.
After randomisation, the participants were provided with the biological activity recording device Polar Activity Monitor A370 (Polar, Łódź, Poland) and were instructed to wear it throughout the study to measure daily activity. This device was chosen for its capability to measure the outcomes related to physical activity and sleep quality chosen for this study. The participants were given the activity devices and were not required to return them after finishing the training protocol; apart from that the participants did not receive monetary rewards for participation or completion of the study.
The study was performed in accordance with the principles set forth in the Helsinki Declaration, and was approved by the Institutional Review Board #991/18 - Bioethics Committee at The Poznan University of Medical Sciences, in Poznan, Poland. The study was retrospectively registered in the clinicaltrials.gov registry (#NCT06190600) on 05/01/2024. Written consent was provided by all participants in the study.
Interventions
High-intensity interval training
Participants allocated to this group received chemotherapy and underwent high-intensity interval training (HIIT) under the supervision of a trained physiotherapist, twice a week for 6 months, concomitantly with the chemotherapy course. The training sessions were supervised by one of two physiotherapists taking part in the study, with at least 5 years of experience working with oncological patients. Training took place in groups of up to 5 participants, and participants were allowed to reschedule a training session and attend another group while maintaining two supervised sessions per week. The training was performed at the following stations: mechanical treadmill (HUR Motion Sprint 600 Med, ASG Wellness & Innovation, Bangkok, Thailand), elliptical bike (HUR Motion Cross 600 Med, ASG Wellness & Innovation, Bangkok, Thailand), cycle ergometer (HUR Motion Cycle 600 Med, ASG Wellness & Innovation, Bangkok, Thailand), rowing machine (Coach M, Kettler, Ense, Germany), and endurance stepper (HUR Motion Stair 600 Med, ASG Wellness & Innovation, Bangkok, Thailand). Training was planned with increasing intensity over the 6-month period. While short-interval (≤ 30 s), low-volume (≤ 5 min work per session) HIIT provides significant benefits for cardiorespiratory fitness, we opted for a protocol with longer intervals and greater volume, which provides greater effectiveness16. Training intensity was measured as a percentage of the HR max calculated as 220 – the participant’s age. We used this method because, from our experience, it is difficult to measure a credible resting HR in patients before exercise in the hospital physiotherapy unit, likely because of stress or excitation. Literature suggests the use of this formula is most appropriate for estimating HR max in persons 30–40 years of age, which was appropriate for our study17. The time of exercise within the HR limits was measured after participants reached the target HR to exclude ramp-up after each break between the work bouts. The training protocol is presented in a diagram (Fig. 1).
The training macrocycle included two mesocycles:
Mesocycle 1 took place over the first month of training and included 4 sets of 1-minute 15 s of exercise at a maximal intensity of 75% HR max. The goal of this part of training was to teach participants to safely perform the required movements with proper technique and to decrease the risk of sustaining injuries during the second mesocycle.
Mesocycle 2 took place over 5 months following the first mesocycle, and included exercise at 80–90% of the HR max. The second mesocycle was subdivided into three periods:
The first period took place during the second month of chemotherapy, and the main training unit included exercises performed in 5 sets18, 1 min 30 s each19.
The second period took place during the third and fourth months of chemotherapy, and the main training unit included exercises performed in 5 sets, 1 min 45 s each.
The third period took place during the fifth and sixth months of chemotherapy and the main training unit included exercises performed in 5 sets, 2 min each18.
During the first mesocycle, the participants performed exercises on four stations in a circuit (rowing machine excluded), and during the second mesocycle, the participants performed all five exercises in a circuit. Within the training unit, between each set, patients performed active resting (walking) for 4 min, which should have normalize HR to 120; the aim was to achieve a 1:2 exercise-to-rest ratio at the final mesocycle19.
Every training unit included a 10-minute warm-up session, approximately a 25-minute main training session, followed by 5 min of stretching and relaxing exercises.
Additionally, throughout the whole macrocycle, the participants were instructed once a week to individually perform 45-minute aerobic training of marching or marching interspaced with running. This training performed without supervision served to reinforce the habit of exercising in patient’s own time for patients to take up exercising after finishing the intervention.
During every training unit the participant’s heart rate was monitored via an additional chest strap (Polar T34, Polar, Łódź, Poland) connected to the monitoring watch The chest strap was chosen to achieve more accurate HR measurement during training compared to optically based wrist devices20.
Control group
Participants allocated to the control group received chemotherapy, and were instructed to perform at least 150–300 min of moderate-intensity aerobic activity or 75–150 min of vigorous aerobic activity throughout the course of chemotherapy, in line with World Health Organisation guidelines on physical activity21. The control group did not perform training under the supervision of a researcher.
The participants in both groups received Polar Activity Monitor A370 watches and were instructed to wear them to monitor daily activity.
Schematic representation of the training protocols used in the study. HR – heart rate, WHO – World Health Organization.
Outcomes
Feasibility of HIIT. The feasibility of HIIT was assessed on the basis of adherence to and retention during the HIIT intervention22. For this study, attendance of at least 70% of the exercise sessions and an 80% retention rate were set as the thresholds of adherence23. Retention was calculated as the percentage of participants who completed the study. Attendance was tracked by the physiotherapist supervising the exercises. During each session adverse events were monitored by asking patients if they experienced symptoms such as nausea, dizziness, persisting muscle or joint pain. Additionally, at the beginning of each session, the participants were asked whether they experienced any adverse events after finishing the previous session. The supervising physiotherapist assessed whether the event was related to training.
Body composition. For all participants, body composition was measured within one week prior to chemotherapy and within one week after finishing the full course of chemotherapy. A Tanita MC-980 bioelectrical impedance analyser (Tanita, Tokyo, Japan) with 6 scanning frequencies (1 kHz, 5 kHz, 50 kHz, 250 kHz, 500 kHz, and 1000 kHz) and 8 electrodes was used to measure muscle mass and body fat mass, both of which are expressed in absolute values. This analyser was chosen to allow for the impedance measurement at 50 kHz, which allows for accurate body composition measurement24. The accuracy of bioimpedance measurements reported by the producer is 0.1 kg. In accordance with the producer’s protocol, one day prior to the measurement, the participants were instructed not to perform vigorous physical exercise, consume alcohol or caffeine, or eat or drink up to 3 h before the measurement. The measurement was conducted with participants standing bare feet on the device’s footpad. The subjects’ height was measured (without shoes) together with weight, and BMI was calculated by dividing weight by height squared.
Handgrip strength. Muscle strength was measured by recording grip strength in both hands. The participants performed this test in a seated position, with their arms at a 90-degree angle, without any prior fatigue. Three measurements were recorded for each hand and the highest value was used as the participant’s result. Grip strength was measured via a Charder mg 4800 dynamometer (Charder, Taichung City, Taiwan). Grip strength was measured at baseline (within a week before starting treatment) and at the end of the treatment (within a week after completing treatment).
Physical activity. Patients were instructed to wear Polar activity devices throughout the duration of the study. The following activities were recorded weekly: number of steps, number of calories burned, and sleep quality: mean daily sleep duration and mean daily duration of long (> 90 s) sleep interruption. The missing data were excluded from the analysis because they were the result of participants not using the activity monitor.
Sample size calculation
We used the between-group difference in continuous outcomes (muscle mass and handgrip strength) for the calculation of the necessary number of participants. A sample size of 40 was required for moderate effect size f = 0.25, statistical significance level = 0.05, and power = 0.8, using a repeated measures ANOVA (interaction between intervention group and time), and considering 1:1 allocation ratio and a 20% attrition rate. The sample size was calculated via G*Power 3.1.9.725.
Statistical analysis
The retention and adherence to the study protocol were assessed by measuring 95% confidence intervals for a proportion via the Wilson method. The normality of the distribution of the continuous variables was measured via the Shapiro-Wilk test, and accordingly to the results, the appropriate statistical test (parametric or non-parametric) was chosen for further comparisons26. For data following the normal distribution, we reported means with standard deviations, and for data not following the normal distribution, we reported medians and first and third quartiles. The baseline between-group differences in outcomes were assessed via the Student’s t-test (normal distribution) or the Mann-Whitney U test (nonnormal distribution) for continuous variables and the chi-square test for categorical variables. The pre-post differences in continuous variables were assessed via paired samples t-test (normal distribution) or Wilcoxon signed rank test (nonnormal distribution). The effect of treatment on a continuous variable was investigated via ANCOVA analysis of covariance, with baseline measurement as covariate, and intervention group as a factor. The outcomes were analysed on the intention-to-treat (ITT) basis.
For all analyses a p-value < 0.05 was considered statistically significant. GraphPad Prism (8.1.1 version) was used for statistical analysis.
Results
Forty participants were assessed for eligibility and 40 met the inclusion criteria and underwent baseline assessment – 19 participants were allocated to the HIIT group, and 21 participants were allocated to the control group. We were unable to recruit the planned 20 participants into the HIIT group due to the COVID restrictions limiting the ability of subjects to travel and for new subjects to participate in in-person sessions. Thirty-seven participants underwent the end-of-treatment assessment after receiving the intended treatment. One participant in the HIIT group resigned without giving a reason, one participant in the HIIT group did not attend the end-of-treatment assessment due to infection, and one participant in the control group was unable to undergo the end-of-treatment assessment due to COVID-19 pandemic restrictions. The flow of participants through the trial is presented in the CONSORT flowchart (Fig. 2).
Participant flowchart.
At baseline, the two groups did not differ in terms of age and body composition, breast cancer characteristics, or type of chemotherapy received. A comparison of the baseline measurements between the two groups is presented in Table 1.
The measurement of participants’ activity revealed a difference in the weekly number of steps (mean: CTR = 88541; HIIT = 71341; Student’s t test p = 0.0196). There was no difference between the two groups in terms of the number of calories burned per week (mean: CTR = 14898; HIIT = 14692; Student’s t test p = 0.8015), mean daily sleep duration (mean: CTR = 424.3 min; HIIT = 426.8 min; Student’s t test p = 0.8179), or mean daily duration of long (> 90 s) sleep interruption (mean: CTR = 32.05 min; HIIT = 33.95 min; Student’s t test p = 0.5086).
Feasibility
All 40 participants who met the inclusion criteria (100%) agreed to participate in the study. The participants were recruited at one site over a period of 17.61 months, resulting in a recruitment rate of 2.27 participants per month. Among the enrolled participants, 37 completed the study while receiving chemotherapy. One participant (in the control group) completed the treatment but was not able to attend the post-therapy evaluation of body composition and muscle strength due to COVID pandemic restrictions; one participant (in the HIIT group) discontinued the intervention without providing a reason; and one participant (in the HIIT group) attended all the training sessions; however, they did not attend the post-intervention assessment due to an ongoing infection. For the HIIT group, this resulted in a retention of 94.74% (18 out of 19 participants), with a 95% confidence interval (95% CI) of 99.07% — 75.36% (retention threshold of the study: 80%). The remaining 18 participants in the HIIT group attended all of the sessions resulting in 100% adherence, with a 95% CI of 100% — 82.41% (adherence threshold of the study: 70%). No adverse events related to physical training were observed in the HIIT group.
Body composition
Analysis of body composition indicated that before treatment, the participants in both groups did not differ in terms of BMI (median (first quartile — third quartile): control = 22.4 (19.3 — 27), HIIT = 23.1 (19.9 — 26.3); Mann-Whitney U test p = 0.8513), muscle mass (median (first quartile to third quartile): control = 44.5 kg (40.2 — 49.2), HIIT = 45.5 kg (43.1 — 48.3); Mann-Whitney U test p = 0.5329), and fat mass (median (first quartile to third quartile): control = 14.7 kg (10.8 — 23.9), HIIT = 19.5 kg (12.8 — 24.8); Mann-Whitney U test p = 0.4364) (Table 1).
There were no significant differences between the pre and post training body composition measurements in the control group. In the HIIT group we observed an increase in weight (p = 0.0271) and muscle mass (p = 0.0041), and a decrease in BMI (p = 0.0232) after treatment (Table 2). With baseline measurement values defined as covariates, there was no significant difference between the two groups in the post-intervention body composition measurements. Figure 3 presents the comparison of the change in body composition between the HIIT and CTR group.
Since the two groups differed in weekly number of steps, we performed an additional analysis including this variable as a covariate in ANCOVA analysis. This analysis also showed no significant differences between the two groups in the post-intervention body composition measurements, although the number of steps did impact the patient’s fat mass (ANCOVA mean number of steps effect p = 0.034). The results of this analysis are presented in Supplementary Table S1.
Effect of high-intensity interval training on body composition of breast cancer patients treated with chemotherapy. Participants undergoing chemotherapy for breast cancer were assigned to two groups: HIIT – performing high-intensity interval training protocol throughout chemotherapy; CTR, control group – instructed to perform physical activity at volume recommended by World Health Organisation guidelines21. Body composition was measured using bioelectrical impedance analysis before treatment and after finishing treatment. The effect of intervention on the change in body composition was assessed using two-way ANOVA test.
Single handgrip strength
Muscle strength analysis revealed that, before treatment, the two participant groups did not differ in grip strength in the arm on the affected side (mean: control = 29.1 kg, HIIT = 32.1 kg; Student’s t-test p = 0.0630) or in the arm on the unaffected side (median: control = 30.5 kg, HIIT = 33.1 kg; Mann-Whitney p = 0.0621) (Table 1). In the control group the handgrip strength on the affected side decreased significantly after treatment (p = 0.0109), with no change in handgrip strength on the unaffected side. In the HIIT group there was no significant change in handgrip strength after treatment (Table 2). With baseline measurement values defined as covariates, the decrease in handgrip strength on the affected side was significantly greater in the control group, compared to HIIT (ANCOVA group factor p = 0.025, between group difference 1.2 kg, 95% CI 0.2 — 2.2). There was no significant difference between the two groups in the handgrip strength on the unaffected side. Figure 4 presents the comparison of the change in muscle strength between the HIIT and CTR groups.
We also performed an additional analysis including this variable as a covariate in ANCOVA analysis. This analysis showed a greater post-intervention grip strength in HIIT compared to CTR group in both affected (ANCOVA group effect p = 0.01) and unaffected (ANCOVA group effect p = 0.028) sides. Additionally, the mean number of steps affected this difference on unaffected side (ANCOVA mean number of steps effect p = 0.005). The results of this analysis are presented in Supplementary Table S1.
Effect of high-intensity interval training on the handgrip strength of breast cancer patients treated with chemotherapy. The participants who underwent chemotherapy for breast cancer were assigned to two groups: the HIIT group, in which a high-intensity interval training protocol was performed throughout chemotherapy was performed; and the control (CTR) group, in which the participants were instructed to perform physical activity at the volume recommended by the World Health Organisation guidelines21.
Discussion
This study aimed to investigate whether HIIT can be successfully employed during chemotherapy in young breast cancer patients.
We assessed the effects of HIIT compared with no additional controlled physical training in a group of young women undergoing chemotherapy for breast cancer. We demonstrated that a six-month course of HIIT, carried out concurrently with chemotherapy, is a feasible training protocol and helps mitigate some of the negative effects of chemotherapy on physical health. Analysis of exploratory outcomes related to the effects of HIIT on physical fitness indicated that HIIT caused no change in body composition measurements. However, employment of HIIT resulted in preservation of handgrip strength on the affected side, compared to a decrease in control group.
In this study, 18 out of 19 participants completed the HIIT protocol while receiving chemotherapy, resulting in a 94.74% retention rate. All of the 18 remaining participants attended every training session (100% adherence). This indicates that the participants met the predetermined adherence threshold, which was completing at least 70% of the training sessions. Additionally, no HIIT-related adverse events were reported. The high feasibility observed in our study exceeded that reported in other similar studies. In the OptiTrain trial, which assigned breast cancer patients undergoing chemotherapy to HIIT coupled with aerobic or strength training, the authors reported a higher drop-out rate: in the resistance and HIIT groups, 65 out of 74 participants (87.84%) finished training, and in the moderate-intensity aerobic and HIIT groups, 60 out of 72 participants (83.33%) finished training12. Importantly, the OptiTrain trial included patients aged 18 to 70 years. Additionally the exercise protocol differed from our protocol – the resistance HIIT group performed resistance training with additional aerobic HIIT, and the moderate-intensity HIIT group performed continuous aerobic exercise followed by aerobic HIIT, whereas our study included warm-up with station HIIT. The high adherence observed in our study might have resulted from the exercise modality we used or from the younger age (18 to 40 years) of the participants. However, the effects of age or exercise modality on feasibility warrant further investigation in a dedicated study. Furthermore, we allowed participants to reschedule training sessions and join other training groups when needed, which may have further improved adherence. While our study included physically active patients between 18 and 40 years of age, HIIT may also be feasible for less active BC patients. A study by Lee et al. recruited sedentary women undergoing chemotherapy for BC to an 8-week HIIT programme, and the participants achieved 82.3% adherence and 100% retention23. Our study also demonstrated favourable adherence compared with supervised aerobic and resistance exercise in BC patients receiving adjuvant chemotherapy, with an exercise adherence of 70.2%28. Furthermore, other studies suggest that HIIT can be successfully utilized both during and after BC treatment, supporting its potential for broader application29. The feasibility of HIIT has also been assessed in patients with other cancer types. Piraux et al. reported a 100% retention rate with 92% session attendance in rectal cancer patients undergoing neoadjuvant chemoradiotherapy30. In a study conducted on esophagogastric cancer patients, a 5-week HIIT programme conducted after neoadjuvant chemo- or chemoradiotherapy also met the author’s feasibility criteria – 81.8% of patients attended at least 15 out of 25 sessions31. This study employed HIIT five times a week for one-hour sessions, which is a higher workload than in our study. Taken together, these findings indicate that, despite its intensity, HIIT can be a feasible and safe training strategy for breast cancer patients. To our knowledge, this study is the first to demonstrate that this applies specifically to young breast cancer patients undergoing chemotherapy.
Our study revealed that completion of HIIT results in positive changes in physical health. Compared with no training, a course of HIIT during chemotherapy resulted in an increase in patients’ muscle mass and weight, and a decrease in BMI, although the two groups did not differ significantly. Low skeletal muscle mass is an important factor in oncological patients and is associated with increased mortality, tumour progression, incidence of toxicity, and reduced quality of life32,33. A systematic review and meta-analysis of different cancer types (not including breast cancer) revealed that the skeletal muscle index significantly decreases over the course of chemotherapy, indicating sarcopenia34. Sarcopenia was also observed in breast cancer patients, where the area of the pectoralis muscle assessed via breast MRI significantly decreased during neoadjuvant chemotherapy, suggesting significant muscle loss35. Muscle loss in patients with breast cancer is a risk factor for poor prognosis36 and is associated with poorer disease-free survival37. Given the importance of muscle loss during treatment as a prognostic factor, offsetting this loss through exercise could be a viable strategy to improve treatment outcomes and enhance patient quality of life.
We also observed a significant decrease in grip strength in the arm on the affected side in participants receiving chemotherapy without physical training and no change in the group performing HIIT. Muscle dysfunction is a significant concern in cancer patients, as lower muscle strength is a predictor of longer hospital stays, fatigue, pain, and reduced quality of life38. Furthermore, breast cancer survivors often experience a significant decline in handgrip strength regardless of treatment type, and this decline is correlated with poorer health-related quality of life39 greater prevalence of depressive symptoms40 and increased cancer mortality41. Our results suggest that HIIT could offset the decrease in handgrip strength observed in patients undergoing chemotherapy. In the OptiTrain trial, the authors reported an improvement in handgrip strength in the HIIT group, likely due to the use of strength training in addition to HIIT11. Those findings suggest that HIIT can mitigate the chemotherapy-induced loss of strength, which could reduce the risk of associated negative symptoms.
The HIIT carried out in the training groups proposed in this study might also offer additional psychosocial benefits. Several studies have indicated that social support is a positive factor for the well-being of breast cancer patients. For example, workplace support is correlated with fewer sickness absences following breast cancer surgery42 whereas family support has been linked to improved self-esteem43. Additionally, higher perceived social support is correlated with reduced intensity of chemotherapy-related symptoms44. Browall et al. examined the effects of physical activity on the health of breast cancer patients, including their psychological health45. The authors demonstrated that participation in group physical training is an opportunity to talk and socialise with people in similar health situations. These relationships often persist after finishing the treatment, offering continuous support. Patients may feel uncomfortable joining public physical activity groups or gyms due to treatment-related reasons, such as alopecia or loss of the breast. A study utilizing focus groups of breast cancer patients demonstrated that patients show interest in participating in group exercise programme, and highlight it as an opportunity to socialize and facilitate exercising more consistently46. Some patients show preference towards more action-oriented group exercise sessions rather than attending support groups47. The patients’ impressions find confirmation in literature – female cancer patients exercising in pairs demonstrate improved emotional well-being, quality of life, and depressive and insomnia symptoms, which were are not observed in patients training individually48. Finally, HIIT might be beneficial for improving cognitive functions49 and a clinical trial predicted to be completed in 2026 aims to investigate the change in cognitive function after HIIT in chemotherapy-treated breast cancer patients50. Thus, the group-based HIIT training proposed in our study may provide both physical and psychological benefits for young breast cancer patients undergoing chemotherapy.
This study was performed on young breast cancer patients. Since the subject group was in relatively good physical health and capable to exercise at high intensity our results can also apply to groups with similar fitness level. This would include young persons with other types of cancer receiving chemotherapy.
The current study has several limitations. First, the main goal was to assess the feasibility of HIIT, which was based on session attendance. However, we did not measure adherence to the training intensity (target HR) throughout each session or work bout. The participants self-monitored the HR via activity devices, and the supervising physiotherapist monitored the work-load to maintain the HR within the required limits; however, we cannot confirm adherence to the training intensity for the entire duration of every work bout. Moreover, the activity differed between the participants in the two groups: the number of steps was measured throughout the treatment, and the weekly number of steps was greater in the control group than in the HIIT group. Including this variable in the analysis revealed a possible increase in grip strength also on the unaffected side in HIIT group, suggesting a more pronounced effect. The participants in the control group were instructed to perform at least 150–300 min of moderate-intensity aerobic activity or 75–150 min of vigorous aerobic activity throughout the course of chemotherapy; however, it is likely that, upon being assigned to a group with no supervised exercise, the participants undertook an additional form of activity. While the weekly number of steps suggests greater activity in the control group, it is important to note that both groups lived relatively active lifestyles. Importantly, daily activity was measured via Polar A370 devices. This model of the activity monitor has been validated in free-living conditions51. The authors of the validation study noted that, owing to high mean absolute percentage errors in most measurements, they recommend that the device be used in addition to established methods. Nevertheless, the authors suggest that the device may be used to measure changes in physical activity rather than to accurately measure physical activity. In our study, we used the device to measure whether the two study groups differed in daily physical activity throughout the intervention and not to report accurate physical activity parameters; however, it should be noted that the assessment of physical activity might be burdened with a significant error. Finally in this study we measured the effects of HIIT training directly after finishing the therapy. The observed effects may not translate into persisting, long-term effects, which is why it is crucial to conduct further research including measurements after months and even years after finishing treatment. Similarly, for the assessment of overall effects of the intervention, patient quality of life should be measured, especially at longer times after finishing therapy.
Conclusions
In conclusion, our study revealed that the use of HIIT throughout the course of chemotherapy in young breast cancer patients is a feasible and well-tolerated intervention and can positively impact patients’ handgrip strength. Further research is needed to assess whether the observed changes persist at long follow-up times and whether HIIT impacts treatment outcomes. The results of the present study show that the six-month course of HIIT used in this study could be a viable option for young breast cancer patients to offset some of the negative effects of chemotherapy.
Data availability
Data is provided within the manuscript or supplementary information files.
References
Ferlay, J. et al. Cancer statistics for the year 2020: an overview. Int. J. Cancer. https://doi.org/10.1002/ijc.33588 (2021).
Kim, H. J., Kim, S., Freedman, R. A. & Partridge, A. H. The impact of young age at diagnosis (age < 40 years) on prognosis varies by breast cancer subtype: A U.S. SEER database analysis. Breast 61, 77–83. https://doi.org/10.1016/j.breast.2021.12.006 (2022).
Tesch, M. E. & Partridge, A. H. Treatment of breast cancer in young adults. Am. Soc. Clin. Oncol. Educ. Book. 42, 1–12. https://doi.org/10.1200/EDBK_360970 (2022).
Schirrmacher, V. From chemotherapy to biological therapy: a review of novel concepts to reduce the side effects of systemic cancer treatment (Review). Int. J. Oncol. 54, 407–419. https://doi.org/10.3892/ijo.2018.4661 (2019).
Scott, J. M., Nilsen, T. S., Gupta, D. & Jones, L. W. Exercise therapy and cardiovascular toxicity in cancer. Circulation 137, 1176–1191. https://doi.org/10.1161/CIRCULATIONAHA.117.024671 (2018).
Sleight, A. G. et al. A new approach to Understanding Cancer-Related fatigue: leveraging the 3P model to facilitate risk prediction and clinical care. Cancers (Basel) 2022, 14. https://doi.org/10.3390/cancers14081982 (2022).
Klassen, O. et al. Muscle strength in breast cancer patients receiving different treatment regimes. J. Cachexia Sarcopenia Muscle. 8, 305–316. https://doi.org/10.1002/jcsm.12165 (2017).
Casla, S. et al. Supervised physical exercise improves VO2max, quality of life, and health in early stage breast cancer patients: a randomized controlled trial. Breast Cancer Res. Treat. 153, 371–382. https://doi.org/10.1007/s10549-015-3541-x (2015).
Mugele, H. et al. High-intensity interval training in the therapy and aftercare of cancer patients: a systematic review with meta-analysis. J. Cancer Surviv. 13, 205–223. https://doi.org/10.1007/s11764-019-00743-3 (2019).
Alzar-Teruel, M. et al. High-intensity interval training among middle-aged and older adults for body composition and muscle strength: A systematic review. Front. Public. Health. 10, 992706. https://doi.org/10.3389/fpubh.2022.992706 (2022).
Mijwel, S. et al. Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the optitrain breast cancer trial. Breast Cancer Res. Treat. 169, 93–103. https://doi.org/10.1007/s10549-018-4663-8 (2018).
Ansund, J. et al. High intensity exercise during breast cancer chemotherapy - effects on long-term myocardial damage and physical capacity - data from the optitrain RCT. Cardiooncology 7, 7. https://doi.org/10.1186/s40959-021-00091-1 (2021).
Toohey, K. et al. The impact of high-intensity interval training exercise on breast cancer survivors: a pilot study to explore fitness, cardiac regulation and biomarkers of the stress systems. BMC Cancer. 20, 787. https://doi.org/10.1186/s12885-020-07295-1 (2020).
Oken, M. M. et al. Toxicity and response criteria of the Eastern cooperative oncology group. Am. J. Clin. Oncol. 5, 649–655 (1982).
Cardoso, F. et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-updagger. Ann. Oncol. 30, 1194–1220. https://doi.org/10.1093/annonc/mdz173 (2019).
Wen, D. et al. Effects of different protocols of high intensity interval training for VO(2)max improvements in adults: A meta-analysis of randomised controlled trials. J. Sci. Med. Sport. 22, 941–947. https://doi.org/10.1016/j.jsams.2019.01.013 (2019).
Lach, J. et al. HR max prediction based on age, body composition, fitness level, testing modality and sex in physically active population. Front. Physiol. 12, 695950. https://doi.org/10.3389/fphys.2021.695950 (2021).
Graef, J. L. et al. The effects of four weeks of creatine supplementation and high-intensity interval training on cardiorespiratory fitness: a randomized controlled trial. J. Int. Soc. Sports Nutr. 6, 18. https://doi.org/10.1186/1550-2783-6-18 (2009).
Ziemann, E. et al. Aerobic and anaerobic changes with high-intensity interval training in active college-aged men. J. Strength. Cond Res. 25, 1104–1112. https://doi.org/10.1519/JSC.0b013e3181d09ec9 (2011).
Gillinov, S. et al. Variable accuracy of wearable heart rate monitors during aerobic exercise. Med. Sci. Sports Exerc. 49, 1697–1703. https://doi.org/10.1249/MSS.0000000000001284 (2017).
Bull, F. C. et al. World health organization 2020 guidelines on physical activity and sedentary behaviour. Br. J. Sports Med. 54, 1451–1462. https://doi.org/10.1136/bjsports-2020-102955 (2020).
Coletta, A. M. et al. High-Intensity interval training is feasible in women at high risk for breast cancer. Med. Sci. Sports Exerc. 51, 2193–2200. https://doi.org/10.1249/MSS.0000000000002048 (2019).
Lee, K. et al. Feasibility of high intensity interval training in patients with breast cancer undergoing anthracycline chemotherapy: a randomized pilot trial. BMC Cancer. 19, 653. https://doi.org/10.1186/s12885-019-5887-7 (2019).
Aldobali, M., Pal, K. & Chhabra, H. In Computational Intelligence in Healthcare Applications. 209–236 (eds Agrawal, R.) (Academic, 2022).
Faul, F., Erdfelder, E., Lang, A. G. & Buchner, A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav. Res. Methods. 39, 175–191. https://doi.org/10.3758/bf03193146 (2007).
Guzik, P. & Więckowska, B. Data distribution analysis – a preliminary approach to quantitative data in biomedical research. J. Med. Sci. 92, e869. https://doi.org/10.20883/medical.e869 (2023).
Brierley, J., Eycken, E., Rous, B. A., Giuliani, M. & O’Sullivan, B. TNM Classification of Malignant Tumours (Wiley, 2025).
Courneya, K. S. et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J. Clin. Oncol. 25, 4396–4404. https://doi.org/10.1200/JCO.2006.08.2024 (2007).
Schulz, S. V. W. et al. Feasibility and effects of a combined adjuvant high-intensity interval/strength training in breast cancer patients: a single-center pilot study. Disabil. Rehabil. 40, 1501–1508. https://doi.org/10.1080/09638288.2017.1300688 (2018).
Piraux, E. et al. High-intensity aerobic interval training and resistance training are feasible in rectal cancer patients undergoing chemoradiotherapy: a feasibility randomized controlled study. Rep. Pract. Oncol. Radiother. 27, 198–208. https://doi.org/10.5603/RPOR.a2022.0036 (2022).
Argudo, N. et al. Feasibility, tolerability, and effects of exercise-based prehabilitation after neoadjuvant therapy in esophagogastric cancer patients undergoing surgery: an interventional pilot study. Dis. Esophagus. 34, 896. https://doi.org/10.1093/dote/doaa086 (2021).
Caan, B. J. et al. Association of muscle and adiposity measured by computed tomography with survival in patients with nonmetastatic breast cancer. JAMA Oncol. 4, 798–804. https://doi.org/10.1001/jamaoncol.2018.0137 (2018).
Nipp, R. D. et al. Sarcopenia is associated with quality of life and depression in patients with advanced cancer. Oncologist 23, 97–104. https://doi.org/10.1634/theoncologist.2017-0255 (2018).
Jang, M. K. et al. Skeletal muscle mass change during chemotherapy: a systematic review and Meta-analysis. Anticancer Res. 40, 2409–2418. https://doi.org/10.21873/anticanres.14210 (2020).
Rossi, F. et al. Muscle mass loss after neoadjuvant chemotherapy in breast cancer: Estimation on breast magnetic resonance imaging using pectoralis muscle area. Eur. Radiol. 30, 4234–4241. https://doi.org/10.1007/s00330-020-06799-5 (2020).
Rossi, F. et al. Evaluation of body computed Tomography-determined sarcopenia in breast cancer patients and clinical outcomes: a systematic review. Cancer Treat. Res. Commun. 21, 100154. https://doi.org/10.1016/j.ctarc.2019.100154 (2019).
Amitani, M. et al. Skeletal muscle loss during neoadjuvant chemotherapy predicts poor prognosis in patients with breast cancer. BMC Cancer. 22, 327. https://doi.org/10.1186/s12885-022-09443-1 (2022).
Christensen, J. F. et al. Muscle dysfunction in cancer patients. Ann. Oncol. 25, 947–958. https://doi.org/10.1093/annonc/mdt551 (2014).
Campos, E. S. A. C. et al. Association of handgrip strength with quality of life in breast cancer survivors: a systematic review and Meta-Analysis. Asian Pac. J. Cancer Prev. 23, 3237–3245. https://doi.org/10.31557/APJCP.2022.23.10.3237 (2022).
Zhang, X. M., Zhang, Z. B., Chen, W. & Wu, X. The association between handgrip strength and depression in cancer survivors: a cross-sectional study. BMC Geriatr. 22, 111. https://doi.org/10.1186/s12877-022-02795-0 (2022).
Zhuang, C. L. et al. Associations of low handgrip strength with cancer mortality: a multicentre observational study. J. Cachexia Sarcopenia Muscle. 11, 1476–1486. https://doi.org/10.1002/jcsm.12614 (2020).
Nilsson, M. I. et al. Adjustment and social support at work early after breast cancer surgery and its associations with sickness absence. Psychooncology 22, 2755–2762. https://doi.org/10.1002/pon.3341 (2013).
Aprilianto, E., Lumadi, S. A. & Handian, F. I. Family social support and the self-esteem of breast cancer patients undergoing neoadjuvant chemotherapy. J. Public. Health Res. 10, 745. https://doi.org/10.4081/jphr.2021.2234 (2021).
Oh, G. H. et al. The effect of perceived social support on chemotherapy-related symptoms in patients with breast cancer: A prospective observational study. J. Psychosom. Res. 130, 109911. https://doi.org/10.1016/j.jpsychores.2019.109911 (2020).
Browall, M., Mijwel, S., Rundqvist, H. & Wengstrom, Y. Physical activity during and after adjuvant treatment for breast cancer: an integrative review of women’s experiences. Integr. Cancer Ther. 17, 16–30. https://doi.org/10.1177/1534735416683807 (2018).
Depenbusch, J. et al. PERSPECTIVEs on supervised exercise programs in people with metastatic breast cancer- a qualitative study in four European countries. Support Care Cancer. 31, 281. https://doi.org/10.1007/s00520-023-07739-x (2023).
Emslie, C. et al. I wouldn’t have been interested in just sitting round a table talking about cancer’; exploring the experiences of women with breast cancer in a group exercise trial. Health Educ. Res. 22, 827–838. https://doi.org/10.1093/her/cyl159 (2007).
Yamada, P. M., Teranishi-Hashimoto, C. & Bantum, E. O. Paired exercise has superior effects on psychosocial health compared to individual exercise in female cancer patients. Support Care Cancer. 29, 6305–6314. https://doi.org/10.1007/s00520-021-06209-6 (2021).
Mekari, S. et al. High-Intensity interval training improves cognitive flexibility in older adults. Brain Sci. 10, 5856. https://doi.org/10.3390/brainsci10110796 (2020).
Wilson, R. et al. Improving cognitive function through High-Intensity interval training in breast cancer patients undergoing chemotherapy: protocol for a randomized controlled trial. JMIR Res. Protoc. 12, e39740. https://doi.org/10.2196/39740 (2023).
Henriksen, A., Grimsgaard, S., Horsch, A., Hartvigsen, G. & Hopstock, L. Validity of the Polar M430 activity monitor in Free-Living conditions: validation study. JMIR Form. Res. 3, e14438. https://doi.org/10.2196/14438 (2019).
Acknowledgements
We would like to acknowledge prof. Przemysław Guzik for his help in editing and structuring the manuscript.
Funding
This research was funded by Greater Poland Cancer Centre, grant number 22/02/2019/F/WCO/0014.
Author information
Authors and Affiliations
Contributions
Conceptualization, M.G., J.K-G., and S.M.; methodology, M.G., J.K-G., and S.M.; validation, M.G., J.K-G.; formal analysis, M.G., I.P., and S.M.; investigation, M.G., J.K-G., M.D., and A.N.; resources, M.Li., A.B-R., E.S-M., J.D., A.M., P.N., M.Lem., W.S., and M.Les.; writing—original draft preparation, M.G., and I.P.; writing—review and editing, M.G., J.K-G., M.D., M.Li., A.N., A.B-R., E.S-M., J.D., A.M., P.N., M.Lem., W.S., M.Les., and S.M. ; visualization, M.G., and I.P.; supervision, M.Li., M.Les., and S.M.; project administration, J.K-G., and S.M.; funding acquisition, M.Li., and S.M. All authors have read and agreed to the published version of the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Górecki, M., Kufel-Grabowska, J., Dudek, M. et al. A randomized trial on the feasibility of high-intensity interval training during chemotherapy in young breast cancer patients. Sci Rep 15, 37591 (2025). https://doi.org/10.1038/s41598-025-18377-0
Received:
Accepted:
Published:
Version of record:
DOI: https://doi.org/10.1038/s41598-025-18377-0



