EmpowerHer: Hybrid Digital Intervention for Breast Cancer Survivors

METHODOLOGICAL DESIGN AND STANDARDIZATION This study is a multicentre, parallel-group, randomized controlled trial (RCT) with a 1:1 allocation ratio conducted across five European countries: Spain, Poland, Ireland, the Netherlands, and Greece. The protocol follows the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. To ensure consistency across all five clinical sites, all physical activity facilitators and researchers will undergo standardized training regarding the delivery of the hybrid program, data collection procedures, and participant safety monitoring prior to study initiation.

RANDOMIZATION AND BLINDING Following baseline assessments, eligible participants will be randomly assigned to either the hybrid digital-facilitator intervention group or the usual care control group. Randomization will be performed using a centralized web-based computerized system to ensure allocation concealment. Due to the nature of the exercise and lifestyle intervention, participants and exercise facilitators cannot be blinded to group assignment. However, outcome assessors responsible for performing the physical and functional tests, as well as the data analysts, will remain strictly blinded to the allocation groups throughout the study.

SAMPLE SIZE CALCULATION The total sample size was determined based on the primary outcome measure (health-related quality of life). To detect a statistically significant and clinically meaningful difference between the intervention and control groups, assuming a statistical power of 80% (1 - beta = 0.80) and a significance level of 5% (alpha = 0.05), a minimum sample size of 118 participants is required. Accounting for an anticipated dropout and attrition rate of approximately 20% over the 12-week intervention and the subsequent 3-month follow-up period, the final recruitment target was established at 147 participants (approximately 29 to 30 participants per country site).

STATISTICAL ANALYSIS PLAN Data will be analyzed using an intention-to-treat (ITT) approach, ensuring that all randomized participants are included in their originally assigned groups regardless of compliance or dropouts. Missing data will be handled using appropriate imputation techniques (e.g., multiple imputation). Descriptive statistics will characterize the sample's baseline demographics and clinical variables. To evaluate the effectiveness of the intervention over time (baseline, 12 weeks, and 3-month follow-up) and between groups, linear mixed-effects models will be utilized. These models will account for the multicentre nature of the trial by treating the study site as a random or fixed effect as appropriate. Statistical significance will be set a priori at p < 0.05.

• EmpowerHer Hybrid Program (Behavioral): A 12-week hybrid physical exercise and health education program. It consists of home-based structured exercise sessions delivered via a dedicated mobile application (minimum of 2 sessions per week) combined with weekly, in-person group motivational and educational sessions led by a trained local facilitator in community settings.

Primary outcomes

• Health-Related Quality of Life (HRQoL) [Baseline (Week 0), Post-intervention (Week 12), and Follow-up (Week 24)]: Evaluated using the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and its breast cancer-specific module (EORTC QLQ-BR23). The EORTC QLQ-C30 incorporates a Global Health Status/QoL scale, functional scales, and symptom scales. The QLQ-BR23 incorporates functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and symptom scales (systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss). All scores are linearly transformed to a 0-100 scale. For the Global Health Status and functional scales, a higher score represents a higher/better level of functioning and quality of life. For the symptom scales, a higher score represents a higher/worse level of symptomatology or problems.

Secondary outcomes

• Physical Activity Levels [Baseline (Week 0), Post-intervention (Week 12), and Follow-up (Week 24)]: Measured using the International Physical Activity Questionnaire (IPAQ). The primary metric will be weekly minutes of moderate-to-vigorous physical activity (MVPA). Total MET-minutes/week will also be calculated. Higher values indicate greater physical activity engagement.
• Lower-Body Muscular Strength (30-second Sit-to-Stand Test) [Baseline (Week 0), Post-intervention (Week 12), and Follow-up (Week 24)]: Assessed using the 30-second Sit-to-Stand test. This test measures the number of times a participant can fully stand up from a seated position on a standard chair (44 cm seat height) and sit down again within a 30-second time limit, keeping their arms folded across their chest. Higher repetitions indicate greater lower-body muscular strength and functional mobility.
• Upper-Body Muscular Strength (30-second Arm Curl Test) [Baseline (Week 0), Post-intervention (Week 12), and Follow-up (Week 24)]: Assessed using the 30-second Arm Curl test. Participants are required to perform as many biceps curls as possible in 30 seconds while sitting on a chair, using a 2 kg dumbbell in their dominant hand (with the arm moving through a full range of motion from complete extension to complete flexion). Higher repetitions indicate greater upper-body muscular strength and muscular endurance.
• Transitional Mobility and Core Strength (30-second Lie-to-Sit Test) [Baseline (Week 0), Post-intervention (Week 12), and Follow-up (Week 24)]: Assessed using the 30-second Lie-to-Sit test, a functional assessment task designed to evaluate transitional mobility. The test measures the maximum number of repetitions a participant can complete within 30 seconds moving from a fully supine position (lying on a flat treatment table or mat) to a fully upright seated position. Higher repetitions reflect better transitional mobility, trunk control, and core strength.
• Intervention Feasibility 1 (Exercise Session Adherence) [Post-intervention (Week 12)]: Measures the feasibility of the intervention, defined as the percentage of prescribed exercise sessions completed by the participants over the 12-week intervention period. This will be calculated as the number of completed sessions divided by the total number of prescribed sessions (24 sessions in total, 2 sessions per week), multiplied by 100. Higher percentages indicate greater feasibility and adherence.
• Intervention Feasibility 2 (Motivational Session Adherence) [Post-intervention (Week 12)]: Measures the feasibility of the face-to-face component of the intervention, defined as the percentage of weekly facilitator-led, in-person motivational and educational sessions attended by the participants in community settings over the 12-week intervention period. This will be calculated as the number of attended in-person sessions divided by the total number of scheduled sessions (12 sessions in total, 1 session per week), multiplied by 100. Higher percentages indicate greater feasibility and adherence to the face-to-face community component.
• Intervention Adoption (Active Mobile Application Engagement) [Post-intervention (Week 12)]: Adoption will be operationalized as active engagement with the intervention through the mobile application. This will include participant-reported interaction with key app features, such as completion of daily wellbeing check-ins (e.g., sleep, energy). Additional indicators such as session-rated perceived exertion (sRPE) and self-reported enjoyment of activities will also be recorded as complementary measures of engagement.
• Intervention Acceptability (System Usability Scale) [Post-intervention (Week 12)]: Assesses the acceptability of the digital health platform using the System Usability Scale (SUS). The SUS is a 10-item questionnaire with five response options ranging from "strongly disagree" (0) to "strongly agree" (4). The overall score is calculated, normalized, and converted to a final scale ranging from 0 to 100. Higher scores indicate greater usability, friendliness, and acceptability of the mobile application (with scores above 68 considered acceptable).

Sex: Female, ages: 18 Years to 65 Years

Inclusion Criteria:

* Women aged 18-65 years.
* History of breast cancer.
* Completed primary treatment (surgery, chemotherapy, and/or radiotherapy; adjuvant hormone therapy is permitted).
* No evidence of active or metastatic disease at enrolment.
* Able to provide informed consent and communicate in the local language.
* Own and are able to use a smartphone.
* Willing to engage in the exercise program.

Exclusion Criteria:

* Cognitive impairment preventing safe participation or questionnaire completion.
* Uncontrolled medical conditions that contraindicate exercise (e.g., unstable cardiac disease).
* Concurrently enrolled in another structured exercise or survivorship study.
* Pregnant or breastfeeding.

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