MENOS4 trial: a multicentre randomised controlled trial (RCT) of a breast care nurse delivered cognitive behavioural therapy (CBT) intervention to reduce the impact of hot flushes in women with breast cancer: Study Protocol

Hot flushes, also known as hot flashes, and night sweats (HFNS) are experienced by up to 70% of women after treatment for breast cancer [29]. HFNS are troublesome for many women, having a significant impact on daily life and sleep quality, with important social consequences affecting employment, personal relationships and quality of life [17]. With natural menopause, HFNS gradually decrease in number and intensity over the post-menopausal years. With breast cancer, HFNS can be more extreme and persistent: experienced by 34% of women more than five years after diagnosis and by 50% of women more than five years from menopause [16]. This is due in part to treatments for breast cancer, which reduce or interfere with the action of oestrogen in the body. Chemotherapy may precipitate an early menopause [30] and tamoxifen and other hormonal treatments cause or exacerbate HFNS [32]. Adjuvant hormone therapies may be used sequentially for a minimum of five years and now up to ten years post diagnosis. The majority of women do not complete the recommended five years of adjuvant hormone therapy, which may be partly due to adverse side effects, such as HFNS, resulting in a 30% increased breast cancer mortality [25, 28].

The most effective treatment for HFNS is hormone replacement therapy, which is contraindicated in ER+ breast cancer [31]. While there are other medications available, such as selective serotonin re-uptake inhibitors (SSRIs) and clonidine, they have unpleasant side effects, and non-medical alternatives tend to lack efficacy [7]. Furthermore, many women prefer not to take medication after cancer, but instead favour self-management of menopausal HFNS [34]. Surveys carried out by the National Cancer Research Institute (NCRI) breast symptoms working party showed that there are no consistent standard care pathways for people with HFNS and that very few women are offered anything in the way of care or management of this problem [15].

There is evidence that a structured cognitive behavioural therapy (CBT), focusing on key elements of the experience of hot flushes and night sweats, delivered in group format, is effective for the alleviation of HFNS in both women with and without breast cancer [1, 12, 26]. In line with the Medical Research Council’s guidance on developing and evaluating complex interventions [11] the theoretical basis and the role of moderators and mediators of the outcomes of CBT have been examined in previous studies. Hunter and Mann [22] developed a theoretical model of HFNS that draws upon symptom perception, self-regulation and cognitive behavioural theories to explain women’s cognitive appraisal and behavioural reactions to symptoms. The model was tested using structural equation modelling [21] and an examination of mediators in MENOS trials [10]. The results clearly suggest that problem rating of HFNS (i.e. the impact of HFNS on daily life) is mediated mainly by beliefs about HFNS, and that changes in beliefs, as well as improvements in mood and sleep, predict positive outcomes with CBT.

There may be a need to develop a variety of ways to deliver the CBT intervention, but group sessions, led by a health professional such as the breast care nurse (BCN), provide a cost effective solution, and were positively viewed in the previous MENOS trial [2]. There are also benefits with group CBT, such as improvements in mood and quality of life, which have not been demonstrated with self-help CBT [1]. Although CBT is known to be effective, it is rarely offered within the NHS for women with breast cancer. It is also not known whether this intervention can be effectively delivered by BCNs in the NHS context. Most women with breast cancer will see a BCN and there is evidence to suggest that it is possible to train BCNs to deliver psychological interventions to a satisfactory level and fidelity [24]. This study will therefore test whether breast care nurses can be trained to deliver CBT in an NHS context to effectively manage HFNS in women who have had breast cancer.

A further consideration is that practical barriers can prevent effective interventions from being delivered in practice, so we will conduct a process evaluation, drawing on May’s Normalisation Process Theory (NPT), [33], to explore potential barriers to implementation. The theory focuses on the dynamic processes that lead to innovations being implemented and integrated into work on an every-day basis. It is therefore a helpful way to assess what happens when multifaceted interventions are introduced into practice. This includes what people’s actions are, collectively and individually, and how and why the desired outcomes are met (or not). The processes that take place when people implement change are described by NPT as coherence, cognitive participation, collective action and reflexive monitoring. The intervention in this trial is an alternative care pathway that includes CBT. The purpose of the process evaluation is to understand the dynamics of the care pathway and identify factors that are important for embedding this intervention into practice. This evaluation will focus on identifying and explaining the extent to which the planned CBT is implemented into practice.

HFNS have been identified as a major physical symptom by the breast cancer research gap analysis [13], requiring research that identifies appropriate interventions to enable women to manage this problem. The research gap analysis also highlights an inadequate translation of research findings into clinical practice and specifically the need to consider how interventions such as CBT can be better integrated to widen access.

The study design is a randomised controlled trial (RCT), with a formal process evaluation. The RCT will be a multi-centre phase III individually randomised controlled trial of a BCN-delivered group CBT intervention versus treatment as usual (TAU).

There is a need for studies that enable effective interventions to be implemented in practice. There is good evidence that CBT is helpful for women with breast cancer [26], yet it is not widely available. It is not yet known whether the intervention can be effectively delivered by BCNs. This study will provide information on both whether the intervention can effectively help women with HFNS and whether and how it can be translated into routine clinical practice.

Despite the fact that CBT has been demonstrated to be effective in relieving the bother of HFNS in women who have had breast cancer, it is not widely available and is rarely offered to women who are suffering these symptoms. One reason for this could be the relatively small number of therapists available to offer this kind of intervention. Most women with breast cancer have access to a BCN and nurses can be effectively trained to deliver psychological interventions. If it can be shown that this intervention can be successfully delivered by BCNs this could make the intervention available more widely. However, there are often other barriers to the implementation of effective therapies, so this study will provide a qualitative evaluation of challenges and barriers and how participating centres overcame these to implement this service into their practice (Figs. 1, 2 and Additional file 1).