High-intensity interval training in combination with aerobic or resistance training for patients with breast cancer : a HIIT to counteract detrimental effects of chemotherapy

With the increasing number of individuals that enter cancer survivorship there is a growing need for interventions that can alleviate treatment-related adverse effects such as fatigue, and that can improve and restore physical functioning and health-related quality of life during and after treatment. After a breast cancer diagnosis, patients with breast cancer show significantly reduced physical activity levels, especially during the adjuvant treatment phase. Today, there is evidence supporting the efficacy of exercise, particularly combined resistance and aerobic training, to improve physiological and health-related outcomes in patients with breast cancer. However, most evidence is based on findings from studies conducted after chemotherapy. The training modality high-intensity interval training (HIIT) has been proven time effective and beneficial for various physiological outcomes. Despite this, data on the effects of HIIT during chemotherapy is limited. Moreover, few of the trials that have assessed exercise training during chemotherapy have included longer follow-ups, especially on objectively measured physiological outcomes, and no trials for patients with breast cancer during chemotherapy have evaluated the effects of exercise on objectively measured pain sensitivity or molecular outcomes in skeletal muscle. To meet the needs that follow the increasingly aggressive treatments for patients with breast cancer, equally progressive countermeasures are needed. Therefore, assessment of the influence of HIIT is highly justified. In this thesis, the aim was to examine and compare the effects of two different supervised exercise programs that included the training modality HIIT with focus on objectively measured physiological and self-reported health-related outcomes over the course of chemotherapy, and 12 months into survivorship. Two hundred and forty women with early stage breast cancer were randomized to 16 weeks of twice weekly supervised resistance combined with high-intensity interval training (RT-HIIT), moderate-intensity continuous aerobic training (AT-HIIT), or usual care (UC).

The results of this thesis showed that compared to the deteriorations found in the UC group over the 16-week intervention, RT-HIIT was effective to counteract fatigue and pain sensitivity and showed improvements in muscle strength, while both exercise groups were effective to prevent declines in cardiorespiratory fitness, gains in body mass, and were effective to alleviate symptom burden. Moreover, exercise-induced specific morphological and functional improvements were found in skeletal muscle. At 12 months, both exercise groups were effective to counteract fatigue, and displayed improved muscle strength compared to deteriorations in the UC group. Additionally, AT-HIIT was effective to maintain body mass, and displayed lower symptom burden, as well as lower sick leave rates compared to the UC group.

Taken together, this thesis shows that adding high-intensity interval training to resistance or aerobic training during chemotherapy in women with breast cancer was feasible, and was shown to be a powerful strategy to manage or prevent many of the short-and long-term adverse effects of treatment and inactivity, as well as to potentially minimize significant societal costs associated with high sick leave rates.

List of scientific papers

I. Mijwel S, Backman M, Bolam KA, Olofsson E, Norrbom J, Bergh J, Sundberg CJ, Wengström Y, Rundqvist H. Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial. Breast Cancer Res Treat. 2018;169(1):93-103.
https://doi.org/10.1007/s10549-018-4663-8

II. Mijwel S, Cardinale D, Ekblom-Bak E, Sundberg CJ, Wengström Y, Rundqvist H. Validation of 2 Submaximal Cardiorespiratory Fitness Tests in Patients With Breast Cancer Undergoing Chemotherapy. Rehabil Onc. 2016;34(4):137- 43.
https://doi.org/10.1097/01.REO.0000000000000030

III. Mijwel S, Cardinale DA, Norrbom J, Chapman M, Ivarsson N, Wengström Y, Sundberg CJ, Rundqvist H. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer. Faseb J. 2018:fj201700968R.
https://doi.org/10.1096/fj.201700968R

IV. Mijwel S, Jervaeus A, Bolam KA, Norrbom J, Bergh J, Rundqvist H, Wengström Y. High-intensity exercise during chemotherapy induces beneficial effects on fatigue, muscle strength, and return to work 12 months into breast cancer survivorship. [Submitted]