Trial Information

Effect of Combined Training Post-treatment Intervention in Lean Body Mass Recovery in Breast Cancer Survival. A Randomised Controlled Trial.

This study will be a 3-month, two arms, randomized controlled exercise intervention trial,
will be developed. After baseline measurements, participants will be randomized into the
treatment and control groups by using a blocked randomization procedure.

This study will be developed through a collaboration between Technical University of Madrid
(UPM) and Cancer Patients Spanish Group (GEPAC). This project will be carried out at the
facilities of the Physical Activity and Sport Science (FCCAFD-INEF) and it was approved by
the Ethical Committee of the UPM.

Women will be recruited from hospitals through posters and oncologist information and the
diffusion of the project that GEPAC will do between their members. Women who present
interest to be contacted will be phoned or mailed a study flyer and will be asked to fill in
an initial questionnaire The intervention will be performed in a social framework. It will
try to provide different skills to women, in order to improve self-trust and self-knowledge.
Other important goal will be to give to women a space where they shared all their
experiences and help women were going through the same situation.

The exercise program will be designed and conducted by qualified in Physical Activity and
Sport Sciences. The exercise program will consist in a combined two days per week of
supervised training program and one day per week of briskly walking by themselves, following
a document, designed by the specialist trainer, which will be given at the beginning of the
program. The intervention will have a duration of 12 consecutive weeks. The intensity will
be increasing progressively from 65% to 85% of heart rate. The intensity will be controlled
by heart rate monitor trademark POLAR FT7. Prescription intensity will be done using
Karvonen equation, recommended method to work with risk population.

Every supervised session will have the same structure and will have a duration of 60
minutes. American College Sport Medicine (ACSM) Guidelines for Cancer Patients will be
followed for the session design. Participants will be divided in groups of 15 per class to
provide more individual attendance.

The first 10 minutes will be the warm up which will include joint mobilizations, different
kinds of movements, briskly walking and running.

Next part will consist in aerobic exercise where the principal goal will be practice
activities what will increase cardiopulmonary fitness and the functional capacity of the
participants. Practiced activities will be "impact activities" which are the activities that
weight is supported by the legs. They activate the bone regeneration and prevent
osteoporosis. Interval training will be performed in this part, with 30 seconds of high
intensity and 3 minutes of active recovery. Then, strength exercises with elastic band and
activities where the women support the own weight will be developed to improve general
strength and increase lean mass. The intensity will be quantified with the number of
repetitions (from 8 to 15) and sets (from 2 to 3).

The last part will be stretching exercises dedicated to improve the joint mobility and the
muscle flexibility of upper body limbs and the general muscles relax after training.

Women will be contacted 3 months after the project to know the real effect in adherence of
the participant and in the global strength.

All adverse events that could occur during the intervention time will be register for the
project coordinator contacting by phone with the patients.

These outcomes were assessed baseline and they were repeated after 12 weeks again.

Lean body mass and fat body mass Percentage of fat mass and percentage of muscle mas will be
assessed by bio impedance, using TANITA BC-601F machine.

Demographics and clinical data Age, marital status, profession, quantity of physical
activity before and after the disease, subtype of tumor, type of resection and type of
endocrine medication will be recorded at baseline measurements.

Anthropometric assessments Weight, high, hip and waist circumferences and waist-hips ratio.
Arm volumetries will be done to check that arm swelling did not increase.

Strength It will be assessed using two types of assessments. First type will be grip
strength in hands, legs and back. Global strength will be assessed by Strength Index, which
will be obtained adding all grip strength values and dividing de result by the participant
weight. Grip Strength dynamomyter T.K.K.5401 to arms strength and T.K.K.5402 to legs and
back strength will be used. Other studies will have used this method in order to obtain
strength levels in breast cancer women demonstrating that is a feasible and safe method in
this population. Second type of strength test will be 8 RM protocol to predict 1 Repetition
Maximum (RM), following National Strength and Conditioning Association guidelines (NCSA
2008) and Mayhew formulae will be used to predict 1 RM. Test will be developed in PANATA
machines.

Cardiovascular Capacity. It will be assessed by a submaximal cardiopulmonary exercise test
following Prior to the start, women will have to complete the PAR-Q test to determine
whether they are able to perform a graded exercise test.

Cardio-respiratory exercise responses will be assessed in each participant using a graded
exercise test (GXT) on a treadmill. The test will be a modification of the Bruce GXT which
was designed for use in clinical and older populations since the submaximal portion of the
test can be done with walking and because it begins at a reduced intensity.

The ACSM guidelines to performance Cardio Pulmonary Exercise Test (CPET) will be followed to
develop or to stop it, if it will be necessary.

Patient Report Outcomes

Quality of Life It is a very important outcome with a large definition related different
concepts such as physical and psychological health, individual independence and social
relationships. It was assessed by FACT-B questionnaire suggested in a review to be used in
this population. The questionnaire presents 38 items and patients have to choose between 5
options (0 totally disagree and 4 totally agree) to describe their grade of accordance with
the specific item

Depression Grade of depression was assessed by Center of Epidemiology Studies - Depression
(CES.D). It was used in previous studies in order to determine the same outcome in breast
cancer population. This test is a Likert scale, which presents 20 items. Patient has to
identify how many times felt in that way during the previous week (from 0 never to 3
always). A score equal to 16 will be regarded as a mild depressive disorder

Health Survey Short Form -36 of Health Survey (SF-36) test will be used to assess Health
Survey. Health status scores are abstractions, which obtain meaning through knowledge of how
the scores are related to other variables and have been already used in cancer patients
population. It presents 36 items and they are divided in 7 dimensions that will be
interpreted together and separately.

Physical Activity Adherence and physical activity that women practice out of the program was
collected by the validate questionnaire Godin Leisure-Time Test which registers times per
week and intensity of the activities that women usually do in a typical week.

All statistical analyses will be done using SPSS Statistics 20.0 program. Confidential
interval will be of 95% and the significance value will be 0.05 to determine the
significance of the results.

Baseline characteristics of participants across the intervention and control groups were
compared using Student t-test for continuous outcomes.

Between women comparisons of those randomized to treatment versus control for changes in
FACT-B, FACT-F, SF-36 and CES-D, scores across months 0-3 will be made using Student t-test,
after determining that adjustment for potential confounders do not alter the results.

Confounders examined included postmenopausal status, BMI status, baseline levels of sport
and leisure-time physical activity.

Pearson correlation coefficients were used to evaluate associations between changes in body
composition and strength and cardio-pulmonary status and changes in PROs scores. All
probability values will be tested with the 2-tailed test.

Follow up 4 months after intervention will be compared with baseline and post intervention
measures using ANOVA test.