Rationale of the BREAst cancer e-healTH [BREATH] multicentre randomised controlled trial: An Internet-based self-management intervention to foster adjustment after curative breast cancer by decreasing distress and increasing empowerment

After the end of primary curative breast cancer treatment, patients go through the transition from ‘patient’ to ‘survivor’ [6, 7]. This transition or re-entry phase [8] is characterized by multiple adaptive tasks on emotional, physical and social domain and sets stage for adaptive long-term survivorship [9]. Topics encountered during the re-entry phase are in principle universal for all BCS and include among others: physical recovery, emotional processing, fear of recurrence, decreasing social support (losing the “safety net” of treatment), resuming professional activities, but also positive life changes (e.g. valuing life more) [6, 7, 10‐12]. Although the majority of BCS eventually adjusts well [13, 14], there is a high information need concerning these topics [15]. However, despite the high information need and universality of re-entry topics, standardized and easy-accessible care to facilitate the transition towards breast cancer survivorship is lacking.

Research on the effectiveness of psychosocial interventions to improve psychological well-being after completion of curative breast cancer treatment is still scarce and inconclusive [10, 16]. With regard to the type of intervention it is suggested that interventions based on cognitive behavioural therapy (CBT) produce larger effect sizes than interventions lacking CBT components [17], and can be effective in reducing distress [18] and improving quality of life in BCS [16]. Also, a central role in survivorship care has been proposed for self-management [5], which is defined as “the individual’s ability to manage the symptoms, treatment, physical and psychosocial consequences and life style changes inherent in living with a chronic condition” [19]. First evidence suggests that self-management interventions in the re-entry phase can facilitate the transition into breast cancer survivorship. For example, pilot testing of a self-management intervention with face-to-face and telephone contact (the Taking Charge intervention [20]) showed beneficial effects on dealing with post-treatment concerns. The Moving Beyond Cancer randomised controlled trial [21] demonstrated beneficial effects of psychoeducational print material and peer modeling videos for BCS on regaining energy in the re-entry phase.

Evidence is growing that Internet interventions can improve psychological well-being in cancer patients [22]. Compared to other methods of delivery, the Internet provides an easily accessible opportunity to reach the large group of cancer survivors. Also, Internet interventions can contain more channels of media to tailor information, and can provide more anonymity compared to face-to-face interventions. Other advantages include avoiding waiting lists, providing consistency of care, and a 24-hour availability [23]. Pilot evidence suggests that an Internet intervention specially designed for posttreatment survivors (Project Onward [24]) can have high utilization rates and reduce depressive symptoms. However, despite the large number of women turning to the Internet for breast cancer-related information [25‐27], evidence-based Internet interventions specifically designed for BCS in the re-entry phase are lacking.

The BREAst cancer e-healTH [BREATH] intervention (‘Catching your breath after breast cancer’) is a non-guided Internet-based self-management website for BCS aiming to foster adjustment after completion of primary curative treatment. Self-management interventions are multi-component and “usually designed to increase the repertoire of participants’ self-management skills within the realities of living with a chronic condition” [28]. The BREATH intervention is a self-management program based on CBT containing components such as psychoeducation, cognitive reframing, goal planning and process evaluation. By using the intervention, BCS will learn how to use these CBT techniques as self-management skills in their daily lives. The BREATH intervention has a fixed content and structure, because it is assumed that “effective self-managers will feel confident in selecting the techniques(s) that they believe will meet their specific needs at a given point of time and in a given environment or situation” [28]. Peer-support is not included in the BREATH intervention, since in the Netherlands support-groups are already widely accessible on the Internet. Also, scientifically the use of Internet-based support groups in cancer patients still needs to confirm long-lasting psychological effects [29]. The BREATH intervention is designed to facilitate and promote adjustment for all BCS, both distressed and non-distressed. In concordance with the stress-coping model of Leventhal (1984), emotional well-being after cancer is defined as the balance between stress and resources [30]. Therefore, in order to target these two aspects of emotional well-being, the aim of the BREATH intervention is twofold: decreasing psychological distress and increasing psychological empowerment, which reflects the individual outcome measure of a patients’ intrapersonal and interpersonal strengths [31].

The primary objective of this randomised controlled trial (RCT) is whether the BREATH intervention is effective compared to usual care in fostering adjustment after curative breast cancer treatment by reducing psychological distress and improving empowerment in BCS. Because BSC with and without elevated levels of psychological distress are included it is hypothesized that through using the BREATH intervention:

This study is designed as a non-blinded, multicentre randomised controlled, parallel-group trial evaluating the superiority of the BREATH intervention compared to usual care after primary curative breast cancer treatment. A consecutive sample of 170 BCS from 6 hospitals will be evaluated in this RCT. Baseline measure (T0) and randomization take place 3 months after completion of primary curative breast cancer treatment. This starting point was chosen because this is in accordance with the standard first follow-up visit after completion of primary treatment as described in the Dutch national breast cancer guideline. Moreover, these 3 months allow for the natural recovery of emotional well-being and adjustment to take place. After completion of baseline measure, participants will be randomised to either intervention or control group. Follow-up measures are respectively 4 months (T1; post-intervention), 6 months (T2), and 10 months (T3) after baseline. The overall study design is captured in Figure 1.

Inclusion criteria are: Women with a histologically proven malignancy of the breast; breast cancer is treated with curative intent surgery and adjuvant chemotherapy and/or radiotherapy; last chemo- or radiotherapy is received ≥2 and ≤4 months; direct access to a computer with Internet connection; basic Internet skills (e.g. in possession of email address); and a good command of the Dutch language. Exclusion criteria are: Men; breast cancer treated only with surgery; metastatic breast carcinoma; previous malignancy except adequately treated cervix carcinoma in situ and treated basal cell carcinoma of the skin; current treatment in psychiatric outpatient clinic.

Participants will be recruited from the oncology and radiotherapy outpatient clinic of a university hospital (Radboud University Medical Centre, Nijmegen), and oncology outpatient clinics of five regional hospital sites (Rijnstate hospital, Arnhem and Zevenaar; Slingeland hospital, Doetinchem; hospital Gelderse Vallei, Ede; Canisius Wilhelmina hospital, Nijmegen; Jeroen Bosch hospital; Den Bosch). All hospitals involved in this multicentre RCT are situated in the southeastern part of the Netherlands.

Recruitment will take place at the end of curative treatment. During the last chemotherapy, or first follow-up visit (3 months after completion of primary treatment) eligible BCS are informed about the BREATH study by a member of their treatment team (oncologist, radiotherapist, or nurse). When BCS are interested in participating in the study, the researcher will have a onetime telephone contact (15–30 minutes) to provide additional information, address questions and second check of the eligibility criteria. Participants will complete informed consent during the next visit at their local hospital, or by mail (depending on the local informed consent procedure of the hospital setting).

The unit of randomization in this study is the individual breast cancer survivor. For each hospital setting, stratified randomization will be based on hormonal therapy. Adjuvant primary curative breast cancer treatment involves hormonal therapy in about 75% of all BCS. During hormonal therapy patients report mood swings and increased fatigue, which can be expected to influence the relationship between the intervention and the outcome variable. After stratification for the use of hormonal therapy, for each hospital a randomised block design will be used using variable block sizes of 4, 6 and 8 to ensure blinded allocation concealment. With an online computerized random number generator, participants will be randomly allocated to receive either usual care or usual care plus access to the online BREATH intervention with an allocation ratio of 1:1. Both the participants, their health care providers, and the researcher are blind to the allocation sequence, but the participant and the researcher are not blind for the randomization outcome.

The intervention is developed by the department of Medical Psychology of the Radboud University Medical Centre Nijmegen in the Netherlands, with technical assistance for ICT applications from Innovatie Psychologische en Psychiatrische Zorg (IPPZ), Utrecht in the Netherlands. The intellectual ownership of the intervention lies with the department of Medical Psychology. During the development of the intervention, patient participation was secured by (filmed) interviews with patients, content feedback by a multidisciplinary reading committee, including BCS and oncology professionals, and usability testing of the final website.

The control group of this RCT has access to usual care. The control condition reflects the natural course of recovery after curative breast cancer treatment. In the Netherlands, standard follow-up of breast cancer involves appointments every three months with a medical professional. The control group may freely use information about breast cancer on the Internet, but does not have access to the protected website with the BREATH intervention.

Demographic characteristics will be gathered by self-report using questionnaires. Information on diagnosis will be obtained from the patient’s physician and medical record. Questionnaires are filled out online with RadQuest software (developed by the department of Medical Psychology, Radboud University Medical Centre, Nijmegen). Participants will receive an invitational email with a link to complete the questionnaires. For an elaborate overview of primary and secondary outcome measures, see Table 2.

Based on the two primary outcomes of the BREATH study, effect on patient level is defined as a decrease in psychological distress (as measured with the SCL-90) or an increase in empowerment (as measured with the CEQ). Therefore, effectiveness of the BREATH intervention is demonstrated when one of the two effects is significant. Sample size calculation is based on the SCL-90, since the SCL-90 has proven sensitive to change through psychological face-to-face intervention in fatigued cancer survivors [36] and information on sensitivity to change of the CEQ is unknown. Significance level of the sample size calculation was adjusted to p ≤ 0.25 to keep the overall chance for type-I errors on 5%. To detect a significant difference (0.25) with 80% power between intervention and control group on the SCL-90, a sample size of 128 BCS (64 in each group) is needed. This sample size calculation is based on a medium effect size of 0.50 of the BREATH intervention, which has proven to be a high effect size for non-guided psychological interventions [74]. Based on a systematic review on attrition in randomised controlled trials of Internet interventions for anxiety and depression [75], we take into account a 25% study drop-out rate. This results in a maximal sample size of 170 BCS that need to be included in the BREATH trial in case of considerable drop-out.

A general linear model for repeated measurements (by the method of mixed linear model) will be used to analyze the effect of the BREATH intervention on the two primary outcome variables (distress and empowerment). Chi square (categorical variables), ANOVA (normally distributed continuous variables), and Kruskall-Wallis (non-parametric variables) will be used to asses baseline characteristics between groups. Analysis will be done according to intention-to-treat methodology.

Recruitment of participants began in 2010. Primary end-points (baseline T0 and post-intervention T1) and all follow-up measures (T2-T3) are expected to be completed in January 2013.

The BREATH study has been approved by the Medical Ethics Committee (CMO) of the Radboud University Medical Centre, Nijmegen in the Netherlands (CMO protocol number 2009/144) [see additional file 1]. The study has also been approved an registered by the local ethical committees of each hospital setting. Registration number of the Netherlands Trial Register is NTR2935.