A randomized controlled clinical trial will be carried out according to the Consolidated Standards of Reporting Trials (CONSORT) Statement (28). The Template for Intervention, Description and Replication Checklist (TIDieR) (29) will be used as a guide to provide transparency and make the intervention replicable. Also, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) was followed to develop this protocol. The protocol of this study has been registered on clinicaltrials.org with the registry number: NCT04965909.

Inclusion criteria: (1) Women aged between 18 and 65 years; (2) diagnosis of stage 0–III breast cancer; (3) primary treatment (surgery, radiotherapy and chemotherapy) completed at least 3 months ago but may still be receiving hormone therapy; (4) pain related to primary treatment in the last 6 months; (5) access to the Internet and an electronic device that allows the use of the applications used in this study and skills for their use or assistance from a close person who has them; (6) ability to communicate fluently verbally and in writing in the language of the research team (Spanish); and (7) approval to participate in the study by the coordinator of the health team that assisted during the course of cancer and its treatment.

Exclusion criteria: (1) another previous type of cancer or breast cancer recurrence in a period of less than 1 year; (2) medical diagnosis of a neurological or autoimmune disease that limits or prevents exercise; (3) some type of pathology that is associated with a contraindication to physical exercise; and (4) the diagnosis of serious psychiatric or neurologic disorders that do not allow the participant to follow orders.

For sampling, non-probabilistic convenience and snowball methods will be used. The sample size was calculated based on the change in FACT-B score between the treatment and control groups at week 12. According to a previous study (30), it is estimated that patients in the intervention group would have a difference in FACT-B score of 10.11 points or more compared to the control group (F-value = 4.86). This difference is above the minimal important difference reported for this measure (7–8 points) (31) and results in an expected partial Eta2 effect size of 0.049. Considering 2 groups, 4 measurements, a type I risk or α 0.05, type II risk or β 0.20 (study power of 80%) and an estimated dropout rate of 15%, a total of 40 participants (20 per group) are needed to be enrolled. Sample size was calculated using the G*Power software, version 3.1.9.7 (Heinrich-Heine University, Düsseldorf, Germany). Figure 1 shows the flow chart of the study.

The sample for this study will be recruited through the dissemination of the project using social networks and with the collaboration of three Spanish breast cancer survivor support associations (Amama Sevilla, AGAMAMA and ASAMMA). Participation in the study will be voluntary. All participants will be facilitated by written informed consent that must be signed to be part of the clinical trial.

This study will have two groups (experimental and control). For assignment, a random method will be carried out using an online tool called ‘random allocation software’ (2.0 version). A stratified allocation will be applied according to the women’s age (≤45 years old or >45 years old). On each of the strata, a randomization will be carried out by blocks of constant size. The assignment sequence will be hidden from the evaluator and the study subjects through an automated assignment system. The preparation of the sequence, the inclusion of the individuals in each group and the assignment of the treatments will be carried out by different members of the research team. On the other hand, the evaluator and statistician will be blinded. Nonetheless, the therapist and subject will not be able to be blinded because of the type of intervention.

The main outcome of this trial is quality of life related to health, measured by the Functional Assessment of Cancer Therapy – Breast (FACT–B+4) (32); five secondary outcomes related to chronic pain experiences will be also measured: intensity of pain, catastrophising level, pain self-efficacy, kinesiophobia, and fear-avoidance behaviors.

An online focused-person therapeutic program, a more up-to-day modality for this type interventions (43), that combines PNE and GEM-Y will be implemented in the experimental group. The sessions will be applied in groups of 10–15 participants, with 3 months being the duration of the entire program. The program will have two parts: the first will involve 8 sessions of PNE during the first month (2 sessions each week, 1 h/session), while the second will involve the use of 16 sessions of GEM-Y during the following 2 months (2 sessions each week, 1 h/session). Figure 3 shows an overview of the experimental intervention.

PNE sessions are divided into two content blocks: Block 1. Knowing my painful process and Block 2. Pain self-management. The Block 1 is divided into three sessions with the following educational topics: sessions (1–3) the concept of pain, acute pain and chronic pain, respectively; session (4) the concept of self-management in relation to pain and healthy habits; sessions (5–8) sleep, stress, diet and exercise habits in relation to chronic pain, respectively. A brief theoretical introduction to the GEM will be also given in the last session. A more detailed description of the content of all PNE sessions and the educational strategies to be followed is presented in the Supplementary material. Figure 4 shows an overview of the PNE programme.

GEM-Y sessions will be organised into four phases: theoretical content of the session, ‘pranayama’ or breathing exercises, ‘dhyana’ or guided meditation, and ‘asanas’ or postures and movements. Moreover, each session will focus on a different part of the body. In this way, yoga is used as a method of therapeutic exercise together with movement representation techniques (44, 45). The program will be delivered by a trained therapist following the principles of progression, gradualness and individualisation proposed by “Twin Peaks” metaphor (22). Thus, at the beginning of the sessions each participant must identify their pain baseline in order to apply an optimal dose of exercise (principle of individualisation). Instructions are given to the participants so that they can always adapt the level of effort to their needs and their progression (more functionality with less associated pain). With regard to the principles of progression and gradualness, since each participant will have a different starting point at the beginning of the programme and will move to their own level, the rate of progression of each participant must also be different. The intensity of the proposed exercises will be progressively adapted to the needs of the group by varying the following parameters: complexity of the ‘asanas’, volume of work (number of exercise blocks and repetitions), control of the relationship work time - rest time ratio. To identify the needs and progress of the group we will use the feedback collected from the participants at the end of each session, and the weekly pain diaries. A more detailed description of the GEM-Y sessions can be found in the Supplementary material.

The whole intervention will be implemented online using the videoconference platform of the University of Seville. Furthermore, WhatsApp and e-mail will be used during the study to give information, provide material or answer queries. Participants’ attendance will be recorded, along with the reasons for non-attendance.

Participants in the control group will only receive traditional biomedical information (26, 36), i.e., explanations of perceived pain based on tissue issues, and general oncological recommendations for analgesia. They will not receive any additional educational or movement-based intervention during the study period. They will be offered the content of the program after the follow-up period for ethical reasons. An online educational booklet will be provide to both groups.

The statistical processing of the data will be conducted with the PASW Advanced Statistics, version 26.0 (IBM Corp, New York, NY, United States). Intention-to-treat principles will be considered for all analyses. The normal distribution of the variables will be assessed with the Shapiro–Wilk test. Descriptive data will be reported as mean (standard deviation), median (interquartile range Q₃–Q₁) or in percentages. Baseline homogeneity will be tested with Chi-square or Fisher’s exact tests; student’s t test or Mann–Whitney U-test.

In those variables in which the 4 measurements are adjusted to normality in both groups, a mixed-model analyses of variance ANOVA (2 × 4) will be used to differences in the outcomes after intervention, with group (PNE + GEM-Y or control) as a between-subject factor and time (the different measurements performed) as a within-subject factor. The hypothesis of interest will be the interaction group by time with an a priori alpha level of 0.05. Partial eta squared (η2) will be calculated to estimate the effect size. If any of the measurements do not adjust to normality, we will use the Friedman ANOVA test and the effect size will be calculated as Rosenthal’s r with the formula: r = Z/√N. All statistical tests will be performed considering a confidence interval of 95%.

This protocol has the approval of the Andalusian Research Ethics Committee (CEI) of the Virgen Macarena - Virgen del Rocío University Hospitals, Sevilla, Spain (protocol code: 2170-N-20; date of approval: 14th June 2021). This clinical trial will follow the recommendations of the Declaration of Helsinki (46) and Spanish legal regulation regarding clinical research in humans (Law 14/2007 on Biomedical Research) (47).

Participants will be verbally informed in a clear and precise way of all aspects of the study. Written information, informed consent and revocation sheet will be given to all participants. Informed consent will be signed before randomization process. All data will be managed in accordance with Spanish Law 3/2018 on the Protection of Personal Data and Guarantee of Digital Rights (48).