Exercise for breast cancer patients undergoing neoadjuvant chemotherapy: the BENEFIT study

Although major progress in breast cancer treatment has been achieved, there is
still a need to further improve prognosis. A novel hypothesis is that exercise
during chemotherapy may have a beneficial effect on prognosis through boosting
the anti-tumoral effect of the cytostatics or enhancing therapy compliance. The
neoadjuvant chemotherapy is an excellent setting to investigate the benefits of
exercise with regard to chemotherapy efficacy and prognosis, as the effects on
the tumor can be immediately explored by effects on the tumor size,
pathological complete response (pCR) and the clinical-pathologic stage (CPS-EG)
score, which have been shown to be good surrogate endpoints for prognosis.
Exercise effects on prognosis might be direct (e.g. via angiogenic effects) or
indirect (e.g. by improving therapy compliance). To investigate these
hypotheses, we aim to conduct a randomized exercise intervention trial (BENEFIT
study).

The major objectives of BENEFIT are (1) to explore the effect of exercise
during neoadjuvant chemotherapy on the anti-tumoral chemotherapy effect,
tolerability and compliance to chemotherapy, patient-reported outcomes
including fatigue, sleep problems, cognitive function, and quality of life;
physical fitness, and biomarkers, and (2) to compare the effects of resistance
exercise vs. aerobic exercise on the above-mentioned endpoints.

The BENEFIT study will be a multicenter randomized controlled trial with 3 arms
comparing resistance exercise (Resistance group) vs. aerobic exercise (Aerobic
group) vs. a *usual care* control (Control group). The exercise interventions
start in parallel with the neoadjuvant chemotherapy (which typically lasts 18
to 24 weeks) and continue until the week before breast surgery (see Figure 1).
The control group will be offered an 18-week exercise program 6 weeks after
surgery. Measurement time points will be before the start of chemotherapy and
before the intervention (T0, baseline), mid-intervention (T1, week 9), at week
19 of intervention or after end of chemotherapy, if later (T2), 6 months after
surgery (T3), and 1 year after surgery (T4). Assessments during chemotherapy
should be performed in the last third of a cycle to reach better comparability.

Patients in the resistance and aerobic exercise groups start the training in
parallel to neoadjuvant chemotherapy and continue until breast surgery.
Patients in the control group receive no training during neoadjuvant
chemotherapy, however, will perform 18 weeks training (resistance training)
after surgery.

Burden:
- Study participation takes time. Patients will visit the UMC Utrecht for
measurements three times. Each visit will take 2 hours.
Patients in the intervention groups are invited to participate in an exercise
program during the course of neoadjuvant chemotherapy. Patients in the control
group are offered a 18-week exercise programme after surgery. Burden of
travelling to the training facilities will be reduced by offering the exercise
program at physiotherapist centers nearby the patients* home.
- Injuries due to exercise can occur, to minimize the risk the intensity of the
exercise program will be gradually increased during the study and supervised by
a trained physiotherapist or fitness instructor
- During the blood draws, a haematoma can occur after blood sampling.
- Incidental findings can arise with maximal exercise testing, which will be
reported to participants.

Benefit:
- We expect that the exercise program will have a beneficial effect on the
patients* health status.