EmpowerHer: Hybrid Digital Intervention for Breast Cancer Survivors

EmpowerHer: Protocol for a Multicentre Randomized Controlled Trial Evaluating a Hybrid Digital Exercise and Education Intervention for Breast Cancer Survivors Across Five European Countries

The goal of this clinical trial is to learn if a 12-week hybrid exercise and education program (EmpowerHer) works to improve health-related quality of life in breast cancer survivors aged 35 to 65.

The main questions it aims to answer are:

• Does the EmpowerHer program improve the everyday quality of life of participants?
• Does the program lower fatigue, anxiety, and depression while raising physical fitness?

Researchers will compare the EmpowerHer program to usual medical care to see if the program works better to help survivors recover.

Participants will:

• Use a mobile application at home at least twice a week for structured exercise.
• Read short educational modules on the mobile application about health after cancer.
• Attend weekly in-person motivational group sessions with a program facilitator.
• Complete health and physical tests at the start, at 12 weeks, and 3 months later.

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.

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.