A Physical Activity Program to Improve Quality of Life and Reduce Fatigue in Metastatic Breast Cancer

Period from the date of randomization to the date of event defined as death from any cause

Period from the date of randomization to the date of event defined as progression of the disease or death from any cause

Health-Related Quality of Life (HRQoL) and fatigue will be measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality Of Life Questionnaire (QLQ-C30). QLQ-C30 questionnaire consists of 30 items to evaluate 5 functioning domains (physical, role, emotional, cognitive, and social), a global HRQoL domain, 3 symptom domains (pain, fatigue and nausea) and 6 single items (dyspnea, insomnia, anorexia, diarrhea, constipation and financial impact). Participants will answer to a Likert scale ranging from "not at all" to "very much" and from "very bad" to "excellent" only for the global HRQoL questions. All scores will be standardized to a 0 to 100 scale according to the EORTC scoring manual. Higher scores represent better functioning, better global HRQoL and greater symptom burden.

All of the secondary health-related quality of life dimensions except the global score and fatigue are evaluated.

Multidimensional aspects of fatigue will be assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-FA12 cancer related fatigue module. EORTC QLQ-FA12 consists of 12 items to evaluated physical, cognitive and emotional domains of cancer-related fatigue. Participants will answer to a 4-points Likert scale ranging from "not at all" to "very much". All scores will be transformed to a 0 to 100 scale and higher scores will indicate greater degree of fatigue.

6-min walking distance

Sit-to-stand

Handgrip strength

Body weight (kg)

Waist circumference (cm)

Hip circumference (cm)

PA level will be measured by the Godin Leisure-Time Exercise Questionnaire (GSLTPAQ). The GSLTPAQ is a short validated self-administrated physical activity (PA) questionnaire which includes three main questions about frequency of low (e.g., easy walking), moderate (e.g., brisk walking), and strenuous (e.g., jogging) leisure-time PA of at least 15 minutes duration in a typical week. The total score is obtained by multiplying frequencies from mild, moderate and strenuous PA by three, five and nine metabolic equivalents respectively and adding these together. Finally this score is divided into three categories (≥ 24 units is equivalent to mild active; between 14 and 23 units is equivalent to moderately active and < 14 units is equivalent to insufficiently active).

Perceived sleep quality will be measured with the Pittsburgh Sleep Quality Index (PSQI) evaluating seven sleep components: (1) sleep quality, (2) sleep latency, (3) sleep duration, (4) habitual sleep efficiency, (5) sleep disturbance, (6) use of sleeping medication, and (7) daytime dysfunction. Each of the seven components is rated on a Likert scale from "Not during last month" (0) to "3 or 4 times per week" (3). The total score resulting from the sum of the seven components ranges from 0 to 21, and a cut off 5 has been found to reflect clinically significant sleep disturbances.

The quality of sleep will also be evaluated by the activity tracker based on automatic recognition of total duration of sleep, duration of deep and light sleep per night for the intervention arm only.

CT scans

Dietary patterns will be assessed using a qualitative food frequency questionnaire composed of 35 items. Participants will answer the question "how frequently do you consume this product" on a Likert-type scale ranging from "never or almost" to "once per day or more" (stating quantity only for the range "once per day or more"). The questionnaire will characterize the consumption of fruits, vegetables, cereals, milk, dairy products, bread, meat, fish, poultry, eggs, starches, plant fat, desserts, sweetened products, non-alcoholic beverages, cold cuts, fried food, fast foods, preprepared meals, crackers, and snacking.

Occurrence of severe toxicity (grade > 2) according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE)

Two 10mL blood samples will be collected before each physical assessment and before starting chemotherapy and at 1st progression.

The following assays will be performed on plasma for the assessment of inflammation and biomarker of sarcopenia: Myostatin, Activin, Cortisol, TNF-alpha, IFN-gamma, IL-1beta, IL-6, Follistatin, GDF5 (BMP14), IL-10, IL-15, NH3, Aminogram.

The levels of lymphocytes, monocytes, neutrophils will be extracted from the data of the routine blood test.

Two 10mL blood samples will be collected before each physical assessment and before starting chemotherapy and at 1st progression.

The following assays will be performed on plasma for the assessment of oxidative stress: Advanced oxidation protein products (AOPP), malondialdehyde (MDA), Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), Xanthine oxidase (XO), and Myeloperoxidase (MPO).

Based on the Five-Factor Model, personality traits will be assessed by the French Big Five Inventory questionnaire (BFI-Fr). The BFI-Fr contains 45 self-descriptive statements that assess the 5 personality traits: neuroticism (which refers to a propensity to experience negative emotions, distress, and anxiety), extraversion (a propensity to be energetic, sociable, and experience positive emotions); openness to experience (the tendency to be curious, imaginative, and to entertain new ideas, values, and experiences); conscientiousness (reflecting self-disciplined, planful, and organized); and agreeableness (which refers to cooperativeness and altruism). Each item was rated on a 5-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). All items will be recoded in the direction of the trait label, and the mean will be taken across items for each personality trait.

The process of change will be evaluated by a validated scale constructs from the transtheoretical model. The process of change scale is a 22-item self-administrated questionnaire to measure eight process of change: self-reevaluation (item 4,8 and 12), reinforcement management (items 7,15 and 12), self-liberation (items 8, 16 and 22), dramatic relief (items 2 and 10), environmental reevaluation (items 3 and 11), counterconditioning (items 5, 13 and 19), helping relationships (items 6, 14 and 20) and consciousness raising (items 1, 9 and 17). Participants will answer to a Likert scale ranging from 1 (never) to 5 (very often). Items in each process of change will be added and then an average score will be calculated. When the average is ≥ 3, the process of change is activated.

Acceptability questionnaire will be assessed by a 21-item questionnaire to evaluate satisfaction concerning the use of connected devices (application, website, quizz, activity tracker).

Performed 3 PA sessions per week

The cancer-related cognitive impairment will be measured by the Functional Assessment of Cancer Therapy-Cognition (FACT-Cog). The FACT-Cog is a validated self-administrated questionnaire in order to assess memory, attention, concentration, language, and thinking abilities. The questionnaire is composed of 37 items with four subscales: patients' perceived cognitive impairments, perceived cognitive abilities, deficits observed or commented on by others, and impact of cognitive changes on HRQoL. Participant will answer how often this situation occurred during the last 7 days on a Likert-type scale ranging from "never" to "several times a day". For both scales, higher scores indicated better perceived cognitive function.