# Exercise as it relates to Disease/High-intensity exercise through chemotherapy for breast cancer, is it worth it?

This Wikibooks page critiques “High-intensity exercise during chemotherapy induces beneficial effects 12 months into breast cancer survivorship” by Mijwel et al. (2019)

## What is the background to this research?

The primary measures of this study is the effects on high intensity interval exercise on cancer related fatigue. The study also included secondary measures which were the quality of life (QoL), symptom burden, muscle strength, body mass, cardiorespiratory fitness and return to work.
Female breast cancer is the most prevalent cancer in the world. One of the most detrimental side effects of cancer is Cancer Related Fatigue (CFR). In Australia 70-100% of the cancer population suffers from CFR. CFR impairs emotional, cognitive, and physical functions which significantly impacts day-to-day life. A way to combat CRF is through exercise both during and after treatment.

## Where is the research from?

All the authors of this paper are associated with the Karolinska Institutet in Stockholm Sweden. The Karolinska Instiutet is ranked 36th in world for universities and is renowned for its cancer research. The authors have a wide range of knowledge in the relationship between exercise and cancer including molecular responses to exercise.
The paper was published in the Journal of Cancer Survivorship, it has an impact rating of 3.671 in 2019 which ranks it in the top 22.97% of all journal articles.
The funding of the research was provided by four Swedish foundations, Radiumhemmets Research Funds, The Swedish Society for Medical research, Cancerfonden and CancerRehabFonden.

## What kind of research was this?

This paper is a perspective study as it is a randomised control trial (RCT). RCT’s are the gold standard for proving cause and effect relationships. As this study is a follow on from a 16-week intervention, the duration of this research is different from other research conducted in the same field.

## What did the research involve?
### Measures

The tests stated below were conducted at baseline, 16 weeks and 12 months
| Measure | Test conducted |
| Self-assessed cancer related fatigue | 22-item Piper Fatigue Scale (PFS) |
| Quality of life | European Organization for Research and Cancer Treatment of Quality-of-Life Questionnaire (EORTC-QLQ-C30) |
| Symptom burden | Memorial Symptom Assessment Scale |
| Return to work | A percentage of how much sick leave the participants took (0%,25%,50%,75%,100%) |
| Level of physical activity | Single item question of whether the participant was meeting the 150 minutes of physical activity or not |
| Cardiorespiratory fitness | Astrand-Rhyming submaximal cycle test |
| Muscular strength | Isometric mid-thigh pull and handgrip |

### Exercise Interventions

Three different categories, resistance training group (RT-HIIT), moderate-intensity aerobic group (AT-HIIT) and the usual care (UC).
Exercise session durations were 60 minutes, supervised by either an exercise physiologist or oncology nurse. The table below highlights the exercise sessions. Borg’s rate of perceived exertion (RPE) was used to determine intensity of exercise.
| | Warm-up | Specific activity of group | Aerobic portion | Cool down |
| RT-HIIT | 5-minute cycle ergometer or treadmill warm Intensity: RPE of 11-12. | Sets: 2-3 Repetitions: 8-12 Intensity: 70% of calculated 1 repetition maximum, progressed to 80% | 3x3minute cycling ergometer Intensity: RPE of 16-18 1 minute active recovery between | 10 minutes dynamic stretching |
| AT-HIIT | 5-minute cycle ergometer or treadmill warm Intensity: RPE of 11-12. | 20 minutes of continuous moderate intensity exercise Intensity: RPE 13-15 Mode: treadmill, elliptical or cycle ergometer | 3x3minute cycling ergometer Intensity: RPE of 16-18 1 minute active recovery between | 10 minutes dynamic stretching |
UC participants of this group were given a written copy of American College of Sports Medicines recommendation of the types of exercises they should complete.

### Strengths and limitations of methodology

Strengths of the methodology were allowing the AT-HIIT intervention group to choose their mode of exercise and having set targets of intensity to ensure continuity. The use of RPE may be a limitation when comparing to other studies as most report percent intensity for exercises.
Multiple measures were used which were all valid for the population. However, they were self-reported which may increase the likelihood of response bias. The main measure, PFS, is suitable for the Swedish population but is limited in its ability for international comparison of the results to other populations.
Other limitations were that physical activity was not measured objectively, nor did the questions ask about types and intensities of activities. Selection bias may have occurred at the 12 month follow up assessment as participants could choose to attend.

## What were the basic results?

The table below describes the significant positive outcomes of both the RT-HIIT and AT-HIIT interventions in comparison to the UC group. The CRF and symptom burden decreased while lower limb and grip strength increased. In the AT-HIIT the effect size for total CRF is small which questions the benefit on CRF. In other sections of the PFS questionnaire the RT-HIIT intervention had a larger effect size in comparison to AT-HIIT. This indicates RT-HIIT could be more beneficial to reduce CRF. Conversely, throughout the paper the authors suggest that the cognitive aspect of CRF in the AT-HIIT group was influential as it may have assisted in the high proportion of participants returning to work, 91% to 69% (p=0.02) when compared to the UC group. This cannot be a causal relationship only a correlation.
| | | RT-HIIT Effect Size | AT-HIIT Effect size |
| Cancer related fatigue | Total | -0.34 | -0.1 |
| Cancer related fatigue | Daily | -0.76 | -0.5 |
| Cancer related fatigue | Affective | -0.60 | -0.39 |
| Cancer related fatigue | Cognitive | NA | -0.13 |
| Symptom burden | Symptom burden | -0.46 | -0.46 |
| Lower limb strength | Lower limb strength | 0.73 | 1.03 |
| Grip strength | Surgery side | 0.7 | 0.71 |
| Grip strength | Non-surgery side | 0.57 | 0.59 |

### Health related quality of life and AT-HIIT

The authors suggest throughout the paper that the AT-HIIT intervention is more beneficial than the RT-HIIT shown through the results in the EORTC-QLQ-C30. This indicates AT-HIIT group may be more effective in increasing QoL.
| | | AT-HIIT effect size |
| Health related quality of life | Constipation | -0.28 |
| Health related quality of life | Appetite loss | -0.66 |
| Health related quality of life | Fatigue | -0.40 |
| Health related quality of life | Emotional functioning | 0.40 |
| Health related quality of life | Role functioning | 0.33 |

### Cancer related fatigue outcomes

The PFS found that CRF was significantly negatively correlated with both lower limb muscle strength (r=-0.20, p=0.035) as well as cardiovascular fitness (r=-0.25, p=0.005). While the EORTC-QLQ-C30 results for CRF came to the same conclusions for lower limb muscle strength (r=-0.25, p=0.008). This data is not specific to an intervention. Thus, the results are that lower limb muscle strength and cardiovascular fitness can be beneficial for reducing CRF.

## What conclusions can we take from this research?

This study concluded that any supervised exercise is more beneficial to QoL as well as CRF in breast cancer patients undergoing chemotherapy in comparison to the usual advice in the long term.
The RT-HIIT group had more significant results in lowering CRF in the PFS, but this may not be comparable outside of the Swedish population. The AT-HIIT intervention results for lowering both body mass and increasing QoL were like many other studies in the field. Further, resistance training may be more beneficial for reducing CRF when combined with either aerobic or high intensity aerobic exercise. Thus, it should be investigated whether a combination of both interventions would be more beneficial in reducing CRF and increasing QoL.

## Practical advice

* Supervised exercise is beneficial while undergoing chemotherapy for breast cancer.
* Consultations of a health professional to understand risks and benefits associated with exercising.
* High intensity aerobic training as well as resistance training might be the most effective plan for reducing CRF and increasing QoL.

## Further information/resources

American College of Sports Medicine
Cancer council (Australia) exercise booklet
EX-MED a not-for-profit organisation for safe exercise prescription for people with cancer

## References

* 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Mijwel S, Jervaeus A, Bolam KA et al. High-intensity exercise during chemotherapy induces beneficial effects 12 months into breast cancer survivorship. J of Cancer Surviv. 2019 Mar 25;13;244-56
* ↑ Breast Cancer [Internet]. [location unknown]: World Health Organization; 2021 Mar 26 [cited 2021 Sep 3]. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer
* 1 2 3 4 Velthuis MJ, Agasi-Idenburg SC, Aufdemkampe G et al. The effect of physical exercise on cancer-related fatigue during cancer treatment: a meta-analysis of randomized controlled trials. Clin Oncol. 2010 Apr;22(3):208-221.
* 1 2 3 Exercise: Cancer fatigue [Internet]. Australia: Royal Australian College of General Practitioners; 2016 Apr [cited 2021 Sep 3]. Available from: https://www.racgp.org.au/getattachment/82956f35-b81b-4b9d-b054-68bb6ccfa2ec/Exercise-for-cancer-fatigue.aspx#:~:text=Exercise%20during%20(and%20after)%20cancer,of%20exercise%20are%20less%20clear.
* 1 2 3 4 Meneses-Echávez JF, González-Jiménez E, Ramírez-Vélez R. Effects of supervised exercise on cancer-related fatigue in breast cancer survivors: a systemic review and meta-analysis. BMC Cancer [Internet]. 2015 Feb 21 [cited 2021 Sep 3];15:77. Available from: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-1069-4
* 1 2 3 4 Falcetta FS, de Araújo Vianna Träsel H, de Almeida FK et al. Effects of physical activity after treatment of early breast cancer: systematic review and meta-analysis. Breast Cancer Res and Treat [Internet]. 2018 Apr 13 [cited 2021 Sep 3];170:455-476. Available from: https://link.springer.com/article/10.1007/s10549-018-4786-y
* ↑ Karolinska Institute [Internet]. [location unknown]: Study Portals; 2021 [cited 2021 Sep 3]. Available from: https://www.mastersportal.com/universities/3/karolinska-institute.html
* ↑ Sara Mijwel [Internet]. [location unknown]: Google Scholar; [date unknown] [cited 2021 Aug 26]. Available from: https://scholar.google.com/citations?user=ryr8L10AAAAJ&hl=en
* ↑ Anna Jervaeus [Internet]. Stockholm: Karolinska Institutet; [date unknown] [cited 2021 Sep 3]. Available from: https://staff.ki.se/people/anna-jervaeus
* ↑ Jessica Norrbom [Internet]. Stockholm: Karolinska Institutet; [date unknown] [cited 2021 Sep 3]. Available from: https://staff.ki.se/people/jessica-norrbom
* ↑ Katherine Bolam [Internet]. Stockholm: Karolinska Institutet; [date unknown] [cited 2021 Sep 3]. Available from: https://staff.ki.se/people/kate-bolam
* ↑ Journal of Cancer Survivorship [Internet]. [location unknown]: SCI Journal; 2020 [cited 2021 Aug 29]. Available from: https://www.scijournal.org/impact-factor-of-j-cancer-surviv.shtml
* ↑ What’s a good impact factor and why it matters [Internet]. [location unknown]: SCI Journal; [date unknown] [cited 2021 Aug 29]. Available from: https://www.scijournal.org/articles/good-impact-factor
* ↑ Hariton E, Locascio JJ. Randomised controlled trails – the gold standard for effectiveness research. BJOG [Internet]. 2018 Dec [cited 2021 Aug 29];125(13): 1716. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235704/
* ↑ Wengström Y, Bolam KA, Mijwel S et al. Optitrain: a randomized controlled exercise trial for women with breast cancer undergoing chemotherapy. BMC Cancer [Internet]. 2017 Feb 6 [cited 20201 Aug 29];17:100. Available from: https://link.springer.com/article/10.1186/s12885-017-3079-x#citeas
* 1 2 3 Mijwel S, Backman M, Bolam KA et al. Adding high-intensity interval training to conventional training modalities: optimizing health-related outcomes during chemotherapy for breast cancer: the OptiTrain randomized controlled trial. Breast Cancer Res and Treat [Internet]. 2017 Nov 14 [cited 2021 Aug 27];168:79-93. Available from: https://link.springer.com/article/10.1007/s10549-017-4571-3
* ↑ Meneses-Echávez JF, González-Jiménez E, Ramírex-Vélez R. Supervised exercise reduces cancer-related fatigue: a systematic review. J of Physiother. 2015 Jan;61(1):3-9.
* ↑ Jakobsson S, Taft C, Östlund U et al. Performance of the Swedish version of the revised piper fatigue scale. Eur J of Oncol Nurs. 2013 Dec;17(6):808-813.