Originally, a proof of concept of the Bone@BC app was developed (2015-2018) by a team of clinicians with specialist experience from the Healthy Living After Breast Cancer research group. The proof-of-concept app was published in 2 languages, Danish and English. The proof-of-concept version provides (1) advice on treatment elements (eg, blood samples and prevention); (2) daily questions about daily living; and (3) private notes. However, the proof-of-concept version of the app did not follow a systematic selection of symptoms to include, and no patients were involved in the design or content of the app (Figure 2).

The proof-of-concept version of the app yielded several noteworthy patient feedback examples, which are as follows:

This study seeks to develop a pilot version of the Bone@BC app based on the above feedback from the patients who used the proof-of-concept version of the Bone@BC app. The pilot version of the Bone@BC app will increase patient friendliness by implementing functionalities developed systematically in collaboration with patients and clinicians to solve patients’ specific needs using this symptom management tool (Table 1).

A systematic review will be undertaken to appraise the current literature and provide an overview of AI-related symptoms reported by postmenopausal women with nonmetastatic ER+ BC. The systematic literature review will be reported according to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols) 2015 statement [27]. A comprehensive search will be undertaken on the following databases: PubMed, MEDLINE, CINAHL, Embase, Cochrane, Web of Science, PsycINFO, and Scopus. The Mixed Methods Appraisal Tool version 2018 [28] will be used for assessing the included studies’ methodological quality.

Stage 2 will be an explorative multimethod stage relying on patient involvement. Moreover, symptoms and concerns identified by the European Organization for Research and Treatment of Cancer (EORTC) Library Item [29] will be selected to be included in the Bone@BC app.

Multimethod data collection will be carried out to explore the symptoms reported by the patients with postmenopausal nonmetastatic ER+ BC in maintenance therapy with AI (letrozole, anastrozole, and exemestane; Figure 3).

In this stage, an electronic Patient Concerns Inventory list (PCI) will be adapted from the English version of the PCI developed by Kanatas et al [40] for patients with BC. The adapted PCI will be modified to fit the app. A PCI is a structured list of frequently asked questions and concerns. It is designed to support and encourage patients to acquire information during their communication with HCPs. The development of the electronic PCI relies on the following steps: (1) translation and linguistic validation according to the Professional Society for Health Economics and Outcomes Research [41]; (2) focus group interview with the patient advisory board; (3) development of a minimum variable product (MVP) app only to test the electronic PCI list; (4) the patient advisory board testing the MVP app and evaluating it in a focus group interview; (5) pilot-test patients (n=15) using the MVP app will be interviewed by semistructured face-to-face interviews; and (6) harmonization meeting in the multidisciplinary research team.

The identified items from the EORTC Library [39] and the PCI will be implemented in the pilot version of the Bone@BC app.

Stage 4 is a convergent, nonrandomized, single-arm mixed methods feasibility study [21] (Figure 4 [20,21,42-49]) investigating the feasibility of the pilot version of the Bone@BC app.

The purpose of this stage will be to explore the patients’ perspectives on feasibility, acceptability, and usability while being offered the pilot version of the Bone@BC app, which will be provided to them as a tool for symptom identification over a period of 12 weeks. Moreover, the consent rate, attrition rate, adherence rate, and retention rate will be explored. Furthermore, the potential changes in self-efficacy, HRQoL, and patient empowerment over time will be measured. The findings from the quantitative data (PRO questionnaires and data in the Bone@BC app) and the qualitative data (patient interviews) will be compared and merged. The intent is to obtain a more comprehensive understanding of the feasibility, usability, barriers, and subgroup of patients who may benefit from using the app.

The feasibility of the study will be assessed by the rate of recruitment and retention over the study duration (12 weeks). The feasibility parameters include adherence rate, acceptability, response rate, representativeness, recruitment rate, technical difficulties, and satisfaction [51].

The acceptability of the pilot version of the Bone@BC app will also be explored by semistructured interviews with a subgroup of the 40-50 invited participants in the study.

The satisfaction survey will be the System Usability Scale–Danish version (SUS-DK) [42] and will be explored in semistructured patient interviews after the intervention. The System Usability Scale is a 10-item questionnaire with 5 responses ranging from “strongly disagree” to “strongly agree” [42]. The final question allows respondents to provide further comments in an open-ended format. The criteria for being satisfied will be a system usability score of ≥68% [42].

The open-source web analytic platform Matomo Analytics [43] will be used to investigate user statistics and traffic in the app. In-app user analytics will be collected to track user behavior such as the number of app sessions, length of app sessions, frequency of use, date the app was first opened, the number of pages, time spent on the pages, and bounce rate.

Health-related outcomes will be collected at baseline upon registration for the pilot version of the Bone@BC app and then at 3 different time points (Table 2).

The health-related ePROs being assessed before and after the study will be the HRQoL by the 30-item EORTC Quality of Life C30 (QLQ-C30) [44]. The HRQoL domains are divided into multi-item subscales: functional (physical, role, cognitive, emotional, and social), symptom (fatigue, pain, nausea/vomiting, and dyspnea), financial adversity, and global health status [44]. The EORTC-QLQ-C30 has proven to be reliable and valid in a range of patient populations and a variety of treatment settings [52].

Self-efficacy will be measured by the Self-Efficacy for Managing Chronic Disease 6-Item Scale (SES6G) [45]. SES6G is a self-administered questionnaire with 6 items on the patient’s perceived self-efficacy on a 10-point Likert scale ranging from “not at all confident” to “totally confident” [45]. Ritter and Lorig [53] conducted 2 new studies and reviewed 8 independent studies to investigate the psychometric properties of the scale. Cronbach α was a minimum of .88 across all studies; minimal floor and ceiling effects were observed; the measure was sensitive to change; and moderate and significant correlations provide convergent validity evidence when measured against selected health indicators [53].

Physical activity will be measured by the Saltin-Grimby Physical Activity Level Scale (SGPALS) [46]. SGPALS is a 4-level scale. The questionnaire measures the level of physical activity as 3 months before the patients were diagnosed with BC and how the level of physical activity is today [46]. The SGPALS is found to be reliable, with a high level of validity and consistency [54].

Anxiety and depressive symptoms will be measured by the Hospital Anxiety and Depression Scale (HADS) [47]. HADS is a validated screening tool and includes 14 questions addressing anxiety and depressive symptoms with 7 items each in the previous 7 days [47]. In an updated literature review, the HADS was found to be reliable with a Cronbach α between .70 and .90 [55].

Patient empowerment will be measured by the Health Education Impact Questionnaire (heiQ) [48]. heiQ is an outcome and evaluation measure for patient education and self-management interventions for people with chronic conditions. heiQ is a validated screening tool and includes 42 questions with the following 4 options for the answer: “strongly disagree,” “disagree, agree,” or “completely agree” [48]. The heiQ is a valid, reliable measure of key dimensions of generic health-related empowerment [56].

Feasibility will be explored by looking at the success threshold, attrition rate, and adherence. The success threshold of ≥60% will be defined as the proportion of informed patients giving consent. The attrition rate will be calculated as the proportion of participants withdrawing from the intervention, leaving no data on outcomes available. The retention rate of ≥85% will be the number of individuals who remained in the study and responded to the daily PRO in 12 weeks. The retention rate and success threshold are based on a recent systematic review of internet-based supportive care for patients with lung disease [57]. Patient adherence will be the proportion of patients completing self-reports for each time point adjusted for withdrawals. The adherence rate is the proportion of patients replying to ≥80% of the daily PRO questions. Adherence to daily completion will be analyzed according to, for example, material status and educational level using the Fisher exact test.

Acceptability will be assessed based on the following predetermined criteria: (1) system usability score ≥68% [42]; (2) patients’ experience identified in follow-up interviews; and (3) HRQoL must be at least at the same level before and after the intervention as measured by the EORTC QLQ-C30 [44].

The quantitative data will be exported to R software (version 4.1.2; R Foundation for Statistical Computing) [58]. All questionnaires will be scored according to the specific manuals. The analysis of the obtained data will be based on CIs and will focus on exploring the longitudinal changes over time. The daily self-report of symptoms will be analyzed using multiple linear regression after the variables have been checked by diagnostic plots to see if they meet the following 5 main assumptions: (1) linearity, (2) homoskedasticity, (3) independence of errors, (4) normality, and (5) independence of independent variables. Descriptive statistics will be performed to describe the sociographic and clinical characteristics. The categorical variables will be reported as frequencies and percentages. Continuous variables will be tested for normality before we decide to report them as mean and SD or median and IQR. In addition, an open-source digital analysis platform (Matomo) [43] will be used to track traffic and user behavior on the app.

The qualitative data will be collected through individual interviews. All interviews will be recorded and transcribed verbatim. The transcripts will be handled systematically in NVivo (QSR International Pty Ltd) [59] to create an audit trail and facilitate transparency [60]. The observational data and interviews will be analyzed based on the 6 steps of thematic analysis outlined by Braun and Clarke [61,62]. Using inductive coding, transcripts will be interpreted, and themes will be generated. Furthermore, researcher triangulation will strengthen the credibility of the results [60].

Due to improvements in diagnostics and treatments, the 5-year survival rate for patients with BC is 90% after the initial diagnosis [70]. During treatments, patients typically have consultations weekly and then gradually reduce to annual visits [71]. During this transition from hospital-based care to health self-management, the patients with BC are encouraged to exercise because of accumulating evidence for the efficacy of exercise training in cancer survivorship [6,71] and, in the majority of cases, adherence to endocrine treatments to reduce the risk of BC recurrence [9]. There is accumulating evidence that many patients with BC (and other patients with cancer) find this transition physically and mentally difficult due to reduced interaction with psychological support from HCP [5-8]. Additionally, ongoing late side effects, for example, pain, fatigue, and loss of appetite [9], and less support from surroundings, given that their surroundings consider them to be healthy [9], are important factors. The late side effects may develop months or even years afterward, and the patients with BC are therefore, in their everyday lives, troubled with being alone with their burdens. A systematic review [72] included 42 studies of self-management education for patients with cancer. Hereof, 16 studies concerning BC suggest that self-management interventions may reduce symptoms of fatigue, pain, depression, anxiety, and emotional distress and increase HRQoL [72].

By equipping patients with the necessary skills, confidence, and knowledge to self-manage their health, they gain increased autonomy and control over their well-being. This empowerment fosters healthy behaviors and encourages proactive measures to prevent long-term illnesses. In many cases, individuals are capable of managing minor illnesses on their own, leading to a decreased reliance on professional assistance. This enables HCPs to allocate their resources and attention toward providing care for patients at higher risk, particularly those with coexisting medical conditions or comorbidities. Around 1 in 5 visits to the general practitioners are made for social needs such as isolation, management, low mood, and anxiety [73]. A systematic review from 2019 [18] found that mHealth apps with interventions focusing on BC survivorship showed a positive effect. By promoting weight loss, improving HRQoL, and decreasing stress. They find that future research is needed to explore the impact of mHealth apps on patients with BC undergoing maintenance therapy [18]. The knowledge of the use of mobile apps for monitoring patients with BC during maintenance therapy is still limited.

The study will be conducted over a duration of 3 years, encompassing well-defined stages. The planning of the study appears to be realistic and feasible within the specified timeline. Stage 4 is deemed feasible, and the deliverables are realistic given that the Bone@BC app has already been implemented in a proof-of-concept version.