Effectiveness of Remote High-Intensity Aerobic Interval Training on Quality of Life and Physical Health in Breast Cancer Survivors: Two Years Follow-Up

Abstract

This study aimed to evaluate the long-term effects of a remotely supervised HIIT program implemented during six months NACT on quality of life (QoL) and physical health outcomes in women with breast cancer, assessed 18–24 months post-intervention. The HIIT intervention study was two arm randomized control trial implementing remotely supervised 4x4 min training at an intensity of 85-95% of peak heart rate for 6 months during NACT. Physical health was assessed by treadmill VO_2peak, 6MWT and sit-to-stand test, and QoL by the EORTC QoL30. Participants were 24 BC survivors who agreed to participate in follow-up 18-24 months after the intervention (HIIT= 13, CG = 11). Results: At follow-up, the HIIT group demonstrated significant difference in change of VO_2peak (p = .046, ES = .169) and time to exhaustion (p = .024, ES= .211). Both groups presented significantly higher 6MWT and sit to stand test results at follow-up compared to pre-NACT (p < .05), while the magnitude of change was not significant. HIIT group results demonstrated moderate associations between 6MWT and Physical Functioning (r = −.674, p = .012) and Emotional Functioning (− .567, p = .043). A remotely supervised 6-months HIIT during NACT showed positive effects on submaximal cardiorespiratory fitness, absolute VO_2peak and muscle strength at 18-24 months follow-up. Moderate negative association between 6MWT and perceived physical and emotional functioning highlighted the complex relationship between physiological outcomes and self-reported QoL. The HIIT can be recommended during NACT to maintain prolonged effects on physical health of BC survivors.

Keywords

breast cancer survivors high intensity interval training quality of life physical health post-intervention effects

Introduction

Breast cancer (BC) is the most common type of cancer among women in Latvia with 1102 first time diagnoses in 2021,¹ and in the world, with >2.26 million new cases in 2020.² BC treatment has different approaches in response to tumor type, stage and progression including endocrine therapy and/or chemotherapy frequently employed together with adjuvant and neoadjuvant systemic therapies. BC survival rates have significantly improved in recent years. For instance, the 5-year survival rate for non-invasive breast cancer is 99%, while the overall 5-year survival rate for invasive breast cancer is 85%.^3,4 Despite significant advancements in BC treatment that have contributed to improved survival rates, the systemic therapies are associated with significant adverse effects, leading to a decline in functional capacity and health-related quality of life (QoL). Moreover, symptoms of BC treatment-related declines in physical, emotional, social and cognitive performance can persist for months or even years following the completion of treatment.⁵

Exercise interventions during neoadjuvant chemotherapy treatment (NACT) for patients with BC have been studied extensively during last decade demonstrating beneficial effects related to reducing treatment-associated side effects.^6,7 A systematic review highlighted the effect of high intensity interval training during different stages of BC treatment.⁸ For example, strength performance significantly increased in the HIIT group compared to the usual care (UC) group.⁹ Furthermore, HIIT demonstrated significant effect in improving cardiorespiratory fitness, physical function, and quality of life in BC patients undergoing neoadjuvant chemotherapy¹⁰ and adjuvant therapy.¹¹ A recent study found that a free-living HIIT program implemented 2 to 3 times per week during 6 months of neoadjuvant chemotherapy was effective in maintaining higher QoL in physical functioning, reducing BC symptoms and systemic therapy-related side effects, for example, physical, social, psychological symptoms and pain.¹²

Current evidence suggests that HIIT induces clinically meaningful benefits for physical health and quality of life in BC patients in a relatively short time during therapy, while long-term effects remain unclear. For example, the long-term effects of HIIT interventions during treatment have only been studied in combination with strength training and moderate-intensity aerobic training.^13,14 In this study the 60 minute training sessions were supervised and provided in the exercise clinic for 16 weeks. The 1- and 2-year follow-up studies demonstrated that both HIIT related interventions had beneficial effects, reducing cancer-related fatigue, symptom burden, and increased muscle strength compared to usual care. The findings provided novel evidence that being involved in an exercise program during chemotherapy can have long-term benefits for women after BC treatment.¹⁴ A recent 8-year follow-up study did not demonstrate long-term, positive effects of 2 comparable exercise programs, (1) home-based physical activity program and (2) a moderate- to high-intensity, combined supervised resistance and aerobic exercise program, implemented during adjuvant chemotherapy treatment compared to the UC.¹⁵

Although these studies enhance understanding of the long-term effect of supervised HIIT interventions, the long-term benefits of independently performed physical exercise programs are still unclear.

This study aimed to explore whether a remotely supervised HIIT program implemented during 6 months of NACT has long-term effects on quality of life and physical health up to 24 months post-intervention.

Methods

Study Design

The randomized controlled trial of the CancerBeat study (clinicaltrials.gov, NCT06522971) including HIIT intervention during NACT has been previously published.¹² Patients with locally advanced non-metastatic BC who were scheduled to receive NACT were enrolled in the study from the Latvian Oncology Center, Riga East University Hospital (REUH) (Latvia) during 2022 to 2023. Eligibility criteria included: (1) age 30 to 65 years; (2) previously untreated primary breast cancer; stage IIA-B, IIIA-C (TNM: T1-4, N0-3, M0) at diagnosis; (3) diagnosis established by core needle biopsy; (4) prescribed doxorubicin/cyclophosphamide-based NACT. The recruited patients were randomly allocated to either HIIT or the control group (CG) at a ratio of 1:1 before the first NACT session. Of 56 enrolled and randomized participants, 37 were included in data analyses. Details regarding the randomization process and blinding have been explained previously.¹² The intervention group (N_HIIT = 17) participated in a remotely supervised HIIT walking program including 2-3 sessions (about 34 minutes) per week for 6 months. The HIIT session started with a 6-minute warm-up period at about 65% to 70% HR_max followed by 4 × 4-minute high-intensity intervals (85%-95% of HR_max) combined with 3 minutes periods of active recovery (55-70% of HR_max). The CG (N_CG = 20) were advised to maintain their habitual lifestyle and follow the standard of care treatment during NACT. The detailed HIIT intervention program and remote supervision has been described previously.¹² The study ethical approval was obtained from the ethical committee of the Latvian Academy of Sport Education (Nr. 1/2021/28/05) and the Scientific Department of REUH (reg. nr. ZD/08-06/01-21/179)

All 37 participants from the CancerBeat study were eligible to be invited for a follow-up assessment between 18 and 24 months after completing NACT. This study was approved by the Medical Ethics Committee of the Riga Stradins University (Nr. 2-PĒK-4/426/2024). In total, 24 (64%) agreed to participate of which 13 were from HIIT group and 11 from CG (see Table 1). Withdrawal reasons were recurrence of BC (1), deceased (3), travel distance (2) did not respond (3), and were not interested (4).

Table 1.

Participant Characteristics.

Variables	HIIT (n = 13)	CG (n = 11)	P
Age, mean (SD)	47.46 (8.41)	52.45 (9.73)	.096
Stage at diagnosis (n)
Stage IIA	5	4
Stage IIB	3	4
Stage IIIA	2	2
Stage IIIC	1	1
Breast cancer subtype
TNBC	3	3
Luminal A	3	2
HER +	2	1
Luminal B, HER −	3	1
Luminal B, HER +	1	4
Time since end of NACT (average in months)	20.53 (3.38)	19.54 (3.11)	.423
Radiotherapy
Yes	10	8
No	3	3

Abbreviations: BMI, body mass index; TNBC, triple negative breast cancer; NACT, neoadjuvant chemotherapy.

Participants

To assess and compare the post-intervention effects of HIIT program across the 3 time points (pre-NACT, post-NACT, and 18-24 months after NACT), the present study included data from 24 participants agreeing to participate in follow-up assessment. Due to the prolonged baseline data collection period and the individualized timing of the intervention, post-intervention assessments were conducted at varying follow-up times. Of all participants, 14 were assessed between 18 and 20 months, and 10 between 21 and 24 months after the NACT. Despite this difference, an analysis comparing the change in primary and secondary outcomes between the 2 subgroups revealed no statistically significant differences. Therefore, the data from both groups were pooled for analysis. This approach is justified by the consistency in the direction and magnitude of changes observed across subgroups, as well as the absence of time-related interaction effects, indicating that the intervention effects were stable across the follow-up.¹⁶ The participant characteristics of HIIT and CG group are presented in Table 1. No clear difference was found between the intervention and control group regarding age (P = .096) and time from the end of NACT and follow-up (P = .423). Of 24 participants involved in this study, 18 received radiotherapy after surgery. Follow-up data were collected during September to December 2024. Participants provided written and informed consent before the assessment session.

Outcome Measures

Quality of Life Assessment

The European Organization for Research and Treatment of Cancer a 30-item questionnaire (EORTC QLQ-C30) version 3.0 was used to assess the quality of life.¹⁷ This instrument includes both multi-item scales and single items consisting of 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items. The range of scores is from 0 to 100, with high scale score representing a higher response level for some items. Thus, a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.¹⁷ In this study, the 5 functioning scales (Physical Functioning, Functional Limitations, Cognitive Functioning, Emotional Functioning, Social Functioning) and Global Health Status were selected for assessment across the 3 time points. Participants completed questionnaires online independently at the end of the assessment session with no time restrictions imposed. Each participant used a unique identification code throughout the study to ensure anonymity.

Physical Health Outcomes

Physical health was assessed using the incremental exercise test, the 30-second sit-to-stand test, 5 × sit-to-stand test and 6 minutes walking test (6MWT).

Incremental Exercise Test

The University of Northern Colorado Cancer Rehabilitation Institute (UNCCRI) Treadmill Protocol was used to assess aerobic capacity parameters of participants.¹⁸ The UNCCRI protocol consisted of 21-one-minute-stages. Treadmill speed and/or incline were progressively increased at the end of each stage. The test was performed on the treadmill (LifeSpan TR2000i) with speed and/or grade increased at each stage of the protocol. The V̇O_2peak, and ventilatory parameters (minute ventilation, VE; respiratory exchange ratio, RER) were measured directly with a Vyaire Vyntus CPX (Germany). Heart rate (HR) was measured continuously throughout the test with Polar H10 sensor. Participants were instructed to maximize their effort, while also they were informed that they could terminate the test at any time. The mean of the 3 highest oxygen uptake measurements over 30 seconds was used to determine V̇O_2peak, VE, and RER. HR_peak was determined from the highest measured heart rate. Objective criteria for exhaustion were: (1) peak heart rate of >95% to the age-predicted maximal; (2) the value on the modified Borg scale of perceived exertion (RPE 9/10); (3) maximal respiratory exchange ratio (RER) > 1.05; (4) a plateau in oxygen uptake measurements with increasing treadmill workload).^19,20 Time to exhaustion (TTE) was recorded at the end of the test.

6MWT

The 6MWT was performed to measure functional capacity associated with endurance levels.²¹ The testing course was 30 m in length in sport gym and the turnaround points marked with orange color cones. Participants were instructed to walk back and forth at their fastest pace, covering as much distance as possible for 6 minutes. Standardized encouragements were given, and remaining time was called out every minute. After 6 minutes, participants were asked to stop, and the completed distance was measured in meters. Directly after the test participants rated their perceived exertion using the modified Borg-Scale.²¹ The Polar H10 sensor was used to monitor HR during the test and the peak HR recorded.

30 Seconds Sit-to-Stand Test and 5-Repetition Sit-to-Stand

Leg muscle strength was assessed by the sit-to-stand (measures taken at 5 seconds (5×STS) and 30 seconds (30STS)) tests.^22,23 The test was performed with a stable chair. Participants were instructed to take standing position, arms crossed with hands on opposite shoulders. On “Start” the participants were asked to perform sitting- to-standing action as many times as possible in 30 seconds. A demonstration was performed beforehand by the evaluator.²⁴ The number of full sit-to-stand actions completed in 30 seconds was recorded. In addition, the 5×STS test was done during the 30STS test performance by assessing the time required to complete 5 repetitions.

Statistical Analysis

All data were analyzed using IBM SPSS Statistics for Windows, version 28 (IBM Corp., Armonk, NY, USA). Participant characteristics were summarized using descriptive statistics, and outcome data were presented as mean ± standard deviation (SD). To assess whether follow-up timing affected the assessment outcomes, the Mann–Whitney U test comparing the change scores (Δ = follow-up − pre-NACT) between the 2 groups was performed. Between-group differences with 95% confidence intervals (CI) were calculated. Delta scores (change from pre-NACT to follow-up) were also computed to quantify the magnitude of change over time. To evaluate longitudinal effects, a general linear model (GLM) with repeated measures was used to test for within-group (time) effects, between-group (group) effects, and Time × Group interactions across the 3 time points (pre-NACT, post-NACT, and 18-24 months follow-up). When significant interaction effects were found, Bonferroni-adjusted pairwise comparisons were performed to explore differences within each group over time, and between groups at each time point, as recommended for repeated-measures analysis. The effect size (ES) was quantified using partial eta squared (n₂^p). The effects were defined as small (n₂^p = 0.01), medium (n₂^p = 0.06), and large (n₂^p = 0.14).²⁵ Spearman’s coefficient of correlation (r) was used to evaluate the association between changes in physical health outcomes and changes in functioning scale scores of EORT-QLQ-C30. A 2-tailed significance level of P < .05 was considered statistically significant.

Results

Physical Fitness

For physical fitness outcomes the HIIT group demonstrated favorable effects for relative VO_2peak (P = .045, ES = 0.186), 6MWT (P = .012, ES = 0.276), sit-to-stand 5×/second (P = .023, ES = 0.233) and TTE (P = .012, ES = 0.257) compared to CG (Table 2). These findings indicate that the HIIT intervention resulted in group-specific fitness gains over time. However, the score changes at follow-up showed greater magnitude for the HIIT group only in the absolute VO_2peak (P = .046, ES = 0.169) and time to exhaustion (P = .024, ES = 0.211). The change in other physical health scores between the groups at follow-up did not present any significant difference (Table 3).

Table 2.

Changes in Physical Health and Quality-of-Life Domains Pre, Post-Treatment and at Follow-Up.

Variable	Within-group differences pre-NACT to 18 to 24 mo after NACT			Between group differences from pre-NACT to 18 to 24 mo after NACT
Variable	Pre-NACT, mean (SD)(a)	Post-NACT, mean (SD)(b)	18-24 mo follow-up, mean (SD) (c)	Mean change (95% CI)	P	Effect size
BMI, mean
HIIT	26.51 (4.40)	24.95 (3.90)	26.00 (3.04)	0.121 (−3.05, 3.29)	.937	0.000
CG	25.10 (2.82)	26.32 (3.28)	25.44 (3.90)	0.121 (−3.05, 3.29)	.937	0.000
EORTC- QLQ-C30
Global health status
HIIT	66.66 (18.32)	62.14 (18.03)	71.79* (19.54)	−12.14 (−24.65, 0.362)	.056	0.170
CG	81.48 (14.30)	72.22 (19.54)	83.33 (10.02)	−12.14 (−24.65, 0.362)	.056	0.170
Cognitive functioning
HIIT	85.90 (20.32)	88.64 (16.57)	74.35 (19.97)	−2.80 (−16.47, 10.86)	.674	0.009
CG	92.59^b,c (8.78)	79.49^a (21.68)	75.92^a (14.69)	−2.80 (−16.47, 10.86)	.674	0.009
Role functioning
HIIT	88.46 (14.24)	80.77 (21.35)	88.46 (18.48)	−5.46 (−14.82, 3.90)	.238	0.069
CG	96.30 (7.34)	81.48 (19.44)	96.29 (7.35)	−5.46 (−14.82, 3.90)	.238	0.069
Emotional functioning
HIIT	68.59 (19.88)	66.03 (26.67)	63.46 (17.85)	−5.57 (−21.64, 10.48)	.477	0.026
CG	67.59 (19.29)	73.15 (21.15)	74.07 (17.89)	−5.57 (−21.64, 10.48)	.477	0.026
Social functioning
HIIT	85.90 (17.80)	76.92 (19.88)	74.35 (23.18)	0.665 (−15.50, 16.83)	.933	0.000
CG	79.63 (27.35)	68.52 (26.93)	87.03 (16.19)	0.665 (−15.50, 16.83)	.933	0.000
Physical functioning
HIIT	88.72b (12.87)	81.03 (17.18)	89.23b (11.06)	3.60 (− 4.83, 12.05)	.383	0.038
CG	86.67 (8.81)	77.04 (16.70)	84.44 (10.54)	3.60 (− 4.83, 12.05)	.383	0.038
Physical fitness outcomes
6MWT
HIIT	618.46^b,c,* (49.14)	609.91^a,c,*(49.34)	669.15^a,b,* (40.98)	48.76 (11.93, 85.60)	.012*	0.276^†
CG	597.56 c (49.78)	579.89 (60.56)	633.56^a,b (39.87)	48.76 (11.93, 85.60)	.012*	0.276^†
Sit-to-stand (30 s) (x)
HIIT	21.31^b,c (4.31)	24.85^a,* (3.21)	24.92^a (3.73)	3.39 (−0.03, 6.82)	.052	0.176
CG	19.11 (4.91)	19.56 (5.72)	22.22 (5.40)	3.39 (−0.03, 6.82)	.052	0.176
Sit-to-stand (5×) s
HIIT	7.31^b,c (1.41)	5.86^a,*(0.84)	5.88^a (0.99)	−1.40 (−2.58, −0.21)	.023*	0.233^†
CG	8.14^c (2.20)	8.34c (2.04)	6.79^a,b (2.21)	−1.40 (−2.58, −0.21)	.023*	0.233^†
VO_2peak test
Value (mL/kg/min)
HIIT	30.74 (3.81)	31.00 (6.95)	30.89 (5.96)	4.29 (0.099, 8.49)	.045*	0.186^†
CG	28.03 (3.92)	24.58 (4.42)	27.13 (4.28)	4.29 (0.099, 8.49)	.045*	0.186^†
VO_2peak test (L/min)
HIIT	2.16 (0.27)	2.06 (0.32)	2.21 (0.31)	0.20 (−0.054, 0.471)	.113	0.121
CG	2.03 (.35)	1.81 (0.39)	1.95 (0.27)	0.20 (−0.054, 0.471)	.113	0.121
V_E (L/min)
HIIT	67.90^c (9.34)	73.85^c (10.95)	84.61^a,b (18.09)	7.08 (−4.25, 18.42)	.207	0.078
CG	66.66 (16.31)	64.00 (15.04)	73.44 (13.31)	7.08 (−4.25, 18.42)	.207	0.078
HR_peak (bpm)
HIIT	170.85 (12.35)	168.92 (13.37)	173.92 (14.53)	−3.01 (−10.48, 4.45)	.417	0.020
CG	172.22 (14.33)	161.00 (18.09)	169.78 (14.73)	−3.01 (−10.48, 4.45)	.417	0.020
RER
HIIT	1.08 (0.13)	1.13 (0.11)	1.16 (0.07)	3.56 (−8.00, 15.12)	.528	0.020
CG	1.05 (0.04)	1.05 (0.05)	1.14 (0.08)	3.56 (−8.00, 15.12)	.528	0.020
TTE (min)
HIIT	16.39 (1.32)	17.2 (1.86)	17.20 (1.62)	1.42 (0.262, 2.59)	.012*	0.257^†
CG	16.27 (1.88)	14.88 (1.90)	15.44 (1.47)	1.42 (0.262, 2.59)	.012*	0.257^†

Abbreviations: CG, control group; HIIT, high intensity interval training; 6MWT, 6 minutes walking test; bpm, beats per minute; RER, respiratory exchange ratio; V_E, minute ventilation; TTE, time to exhaustion.

Significantly different (P < .05) from the respective value within group comparisons: ^apre-treatment, ^bpost-treatment, ^c12-18 months post-treatment. Superscripts indicate within-group differences (Bonferroni-corrected).

P < .05 indicates significant changes between groups.

†

Indicates significant effect size.

Table 3.

Delta Values (Change in the Scores From Pre-Treatment) at 18 to 24 Months for HIIT and CG.

Variable	HIIT	CG	Mean difference (95% CI)	P	Effect size
EORTC- QLQ-C30 ∆General health	5.13 (12.51)	1.85 (15.46)	3.27 (−9.18, 15.73)	.589	0.015
∆Cognitive Functioning	−11.53 (22.95)	− 16.66 (16.66)	5.12 (−13.57, 23.82)	.574	0.016
∆Role Functioning	0.00 (19.24)	−0.00 (11.78)	0.001 (−15.07, 15.07)	1.00	0.000
∆Emotional Functioning	−5.12 (23.45)	6.48 (14.29)	−11.60 (−29.96, 6.74)	.202	0.080
∆Social Functioning	−11.53 (24.89)	7.40 (18.84)	−18.94 (−39.44, 1.55)	.068	0.157
∆Physical Functioning	−3.11 (10.59)	−5.74 (19.11)	7.62 (−12.33, 7.06)	.292	0.005
Physical Fitness outcomes ∆6MWT	50.69 (30.87)	32.00 (28.29)	18.69 (−6.57, 43.95)	.139	0.097
∆HR max during 6MWT	8.15 (10.87)	7.27 (16.32)	0.881 (−10.69, 12.45)	.876	0.001
∆Sit-to-stand (30 s) (×)	3.61 (3.50)	3.72 (4.51)	−0.112 (−3.50, 3.28)	.946	0.000
∆Sit-to-stand (5×) s	−1.45 (1.18)	−1.49 (2.09)	0.043 (−1.37, 1.45)	.951	0.000
VO_2peak test ∆VO₂ at AT (mL/kg/min)	0.145 (3.63)	−1.23 (2.31)	1.385 (−1.255, 4.025)	.288	0.051
∆VO₂ (L/min)	0.051 (0.18)	−0.106 (0.17)	0.158 (0.003, 0.313)	.046^*	0.169^†
∆V_E (L/min)	15.70 (14.30)	5.90 (10.15)	5.15 (−0.88, 20.50)	.070	0.141
∆HR_peak (bpm)	3.07 (10.68)	−3.09 (10.15)	6.16 (−2.70, 15.04)	.164	0.086
∆RER	0.073 (0.13)	0.058 (0.12)	0.01 (−0.09, 0.12)	.780	0.004
∆TTE (min)	0.80 (1.78)	−0.82 (1.46)	1.63 (0.239, 3.03)	.024^*	0.211

P < .05 indicates significant changes between groups.

†

Indicates significant effect size.

Within-group analyses demonstrated that both groups, HIIT and CG, on average completed significantly longer distance in 6MWT at follow-up compared to pre- and post-NACT (P < .05). Significant improvements in both Sit-to-stand test items (30STS and 5×STS) were presented by the HIIT group at follow-up compared to pre-NACT (P < .05). The CG presented significant improvements in 5×STS results at follow-up compared to pre- and post-NACT (P < .05). Significant gains for HIIT group at 18 to 24 months post-NACT were found in average values of V_E (minute ventilation) outcomes compared to pre-and post-NACT (P < .05; Table 2).

Quality of Life (QoL)

In this study outcomes, the Global Health Status and the 5 functional scales of the EORTC QLQ-30 were analyzed. The HIIT group did not present favorable effects at follow-up. Between-group analyses presented significantly higher average General Health Status scores in CG at the 18 to 24 month post-NACT compared to the HIIT group. Furthermore, the CG demonstrated a significant decline in Cognitive Function (Table 2). The change in QoL outcomes between the groups at follow-up showed no significant difference (Table 3).

Association Between Changes in Physical Fitness and Quality of Life Outcomes

Significant moderate negative associations on changes were found only in HIIT group between 6MWT and Physical Functioning (r = −.674, P = .012) and Emotional Functioning (−.567, P = .043).

Discussion

This study aimed to assess whether remotely supervised HIIT program during NACT produced long-term benefits in physical health outcomes in BC survivors up to 24 months after completion of the intervention. This is the first study in Latvia to explore if the exercise induced health benefits are maintained up to 2 years after the intervention. Scientific reports presenting long-term effects of HIIT interventions for BC survivors are very limited. Therefore, these findings contribute the existing literature with evidence-based information for BC survivorship and long-term clinical effects.

Physical Health Outcomes

The present study highlighted several novel findings related to long-term benefits in physical health outcomes of BC survivors participating in HIIT during 6 months of NACT. Notably, over the 18 to 24 month follow-up period, HIIT group presented significant improvements in absolute VO_2peak and time to exhaustion (TTE) compared to the CG. In contrast, relative VO_2peak remained unchanged, consistent with previous studies reporting stable relative values due to unaltered body mass despite enhanced cardiorespiratory fitness.²⁶ While no significant differences in average body mass were observed between groups across assessments, substantial individual weight variations from pretreatment to follow up (15-20 kg) were noted. These findings align with earlier evidence,²⁷ which attributed improved absolute VO2_peak to enhanced oxygen delivery and cardiac efficiency, with minimal changes in relative VO_2peak due to weight variability. Furthermore, a 12-month structured exercise intervention in early-stage BC survivors similarly demonstrated increased absolute VO_2peak, primarily caused by improved cardiac output rather than peripheral adaptations, as indicated by only modest changes in arteriovenous oxygen difference.²⁸

This study results showed significant differences in average 6MWT scores between the HIIT group and the CG both before NACT and at follow-up (P < .05). However, the average differences were 21 and 36 m in the 2 respective assessments. There is no minimal clinically significant difference reported for the BC patients or BC survivors, unlike the 25 m has been established in patients with coronary artery disease.²⁹ Although not statistically significant, participants in the HIIT group were slightly younger than those in the CG, which could have influenced the 6MWT results. For example, Ying et al³⁰ reported that age had a significant negative impact on 6MWT distance, with a decrease of 2.6 m per additional year of age. Furthermore, separate analyses of both groups, HIIT and CG, demonstrated significant improvements in average scores of in sit-to-stand 5 times performance test outcomes at follow-up. Travier et al³¹ implemented supervised 18-week aerobic and strength exercise program which demonstrated beneficial effects on submaximal cardiorespiratory fitness and muscle strength 9 months after intervention. The improvements in the CG scores at follow-up may be attributed to natural post-treatment recovery, as previous studies have shown that common side effects of breast cancer treatment (eg, muscle weakness, neuropathy, and fatigue) tend to diminish within 1 to 2 years, potentially leading to enhanced physical performance outcomes.^6,23

Overall, the greater improvements observed in multiple physical health outcomes in the HIIT group may be attributed to the combined effects of enhanced leg muscle strength and increased aerobic fitness. These findings were similar to other interventions implemented at different periods of BC treatment. For example, Dong et al³² found significant effect of 12-week internet-based remote resistance and aerobic training on muscular strength and cardiopulmonary endurance in BC patients directly after chemotherapy/postoperative radiotherapy. The follow-up study after 1 year showed beneficial effects in muscle strength but not in VO2_peak.³³ The interventions combining resistance exercise and aerobic exercise training for the duration of chemotherapy may result in some longer-term and late effects for physical health outcomes.^31,34 While authors concluded that presented effects could be caused by increased physical activity levels during follow-up, it might be challenging to draw conclusions from results of this study without monitoring the lifestyle habits during follow up time period. During follow-up assessment session participants were asked about their physical activity levels in previous 6 months. The anecdotal notes revealed that some participants from both groups reported engaging in low intensity physical activities 1 to 2 times per week, for approximately 50 to 60 minutes per day (eg, walking to the bus stop/ train station or to the work office, gardening, cleaning etc.).

A moderate negative association was found in HIIT group between changes in 6MWT results and Physical Functioning (r = −.647) and Emotional Functioning (−0.567) QOL scores, indicating that participants who exhibited greater improvements in 6MWT distance, tended to report smaller improvements, or even potential declines in perceived physical and emotional functioning. These findings emphasize the complexity of the relationship between physiological and self-perceived health in BC survivors. Although HIIT intervention demonstrated significant effects in objective measures of physical health (absolute VO2_peak, TTE), the subjective experience of these changes appears to be more nuanced up to 2 years after the intervention. Similar outcomes were demonstrated in previous studies concluding that physical improvements following exercise interventions did not always correspond with equivalent improvements in QoL measures.^34,35

Quality of Life: Functional Scales of EORTC-QLQ-C30

The study outcomes demonstrated that there was no significant change in self-reported scores of EORTC QLQ-30 scales from pre-NACT to 18 to 24 months follow-up stage. In this study, participants reported slightly above average levels across all functioning scales, with the highest score observed in Role Functioning in both groups (Table 2). These findings were somewhat similar to Mijwel et al¹³ and Bolam et al¹⁴ demonstrating long-term effects of 16-week HIIT combined with resistance or moderate intensity aerobic training outcomes on health-related variables of BC patients in 4 time points, from baseline to 2 years. In their study the average self-reported scores in functioning scales were >50 with the highest mean scores in Physical Functioning. In this study within-group analyses demonstrated that HIIT group reported significantly higher level of Physical Functioning before NACT and at 18 to 24 months follow-up compared to post-NACT phase (P < .05). In both groups subscale scores returned close to baseline at follow-up. Similarly, previous studies did not find significant effect of exercise during chemotherapy on Physical Functioning and overall health related QoL score change in BC survivors at the follow-up stage.^13,14 However, different outcomes were reported by Binyam et al¹⁵ showing that the exercise group tended to decline in Global Health related QoL at 6 to 9 months post-intervention, while there were no differences between groups after 8 years.

The elevated General Health outcomes in pre-treatment and in follow-up reported by the CG may be influenced by the variability in how oncology specialists communicated the diagnosis to patients, as each practitioner may adopt a distinct approach. Given that the pre-treatment assessment was conducted within 1 week of diagnosis and prior to the initiation of NACT, participants may have subjectively interpreted the information regarding their BC diagnosis, potentially impacting their responses. Previous studies have demonstrated that improved illness acceptance among patients contributes to better health-related QoL by mitigating negative disease-related perceptions and fostering a greater sense of well-being.³⁶

The current study demonstrated that Cognitive functioning tend to decline in both groups from pre-NACT to 18 to 24 months follow-up with significant decrease of average scores for CG. For example, anecdotal notes taken during the visit confirmed that participants had subjective memory complaints that negatively impact their work and personal life. According to previous studies, multiple factors might affect cognitive function of BC survivors for several years after systemic therapies, for example, fear and uncertainty on risks of recurrent cancer,³⁷ association with menopausal symptoms,³⁸ psychological factors (stress, anxiety).¹⁵

Limitations and Future Implications

This study has a small sample size since participants were recruited from a previous project involving only 37 women with BC,¹² of which 65% (24 women) agreed to participate in follow-up assessment. Previous longitudinal studies have reported large variability in drop-out rates after one to five years post-intervention, from about 20% (Bolam et al¹⁴) to 35%-45%.^39,40 The variability in the timing of the conclusion of the HIIT intervention among participants, approximately 6 months, represents another potential limitation of this study. The variations in both aspects, time-based and drop-outs, could impact the study outcomes assessing the intervention effects in follow-up assessment. While participants from both groups reported involvement in light physical activities at least 1 to 2 times per week during past 6 months, the more extended objective (eg, using accelerometers) data collection on daily physical activities would benefit analyses of data during follow-up period.

The strength of this study is assessment of long-term (18-24 months) effects of remote 6 months HIIT intervention during NACT on physical health of BC survivors. From this perspective, this study is important as it demonstrates evidence-based practice for designing and implementing rehabilitation protocols during NACT for BC patients.

Future studies should emphasize the benefits of physical activity in long-term health maintenance by exploring individualized exercise prescriptions that align with the specific needs and post-treatment goals of each BC survivor. Additionally, research should investigate practical strategies to integrate remotely monitored exercise into daily life based on individual’s personal and environmental options.

Conclusions

Participants in the HIIT group 18 to 24 months after intervention were generally still experiencing favorable differences in aerobic endurance outcomes compared to CG. Both groups presented declining trend in cognitive functioning reporting subjective complaints on memory skills. The high intensity interval training during the 6 months of NACT may lead to long-term benefits of cardiovascular health related outcomes.

Footnotes

Acknowledgements

We thank all participants for their participation.

ORCID iDs

Aija Klavina

Edgars Bernans

Ethical Considerations

The current study was approved separately by the Medical Ethics Committee of Riga Stradins University (Nr. 2-PĒK-4/426/2024).

Consent to Participate

All participants provided written informed consent prior to involvement in the study.

Author Contributions

Author AK and SL designed the study and wrote the manuscript. SL contacted and recruited participants. Authors SL, EB and MV collected and analyzed the data. EB edited the manuscript. All authors reviewed and approved the final manuscript.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study has been funded by the project “RSU internal and RSU with LSPA external consolidation” No. 5.2.1.1.i.0/2/24/I/CFLA/005. Researcher Grant “Physical activity for prevention of breast cancer recurrence: a longitudinal study of molecular mechanisms” (Cancerbeat-2), No. RSU/LSPA-ZG-2024/1-0001

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.

Data Availability Statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

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