1. Introducción

The stress associated with a diagnosis of breast cancer results in a myriad of emotional and physical symptoms that negatively impact the health and quality of life of patients during all phases of treatment. One of the most common complaints involves the patients’ sleep. Sleep disturbances include a number of sleep disorders: insomnia, hypersomnia, sleep related breathing disorders, sleep movement disorders (restless leg syndrome), circadian rhythm sleep-wake disorders, and parasomnias. For the purposes of this article, the authors will focus on insomnia specifically as it is the most common cancer related sleep disorder. However, we acknowledge that many patients have underrecognized sleep disorders such as sleep apnea that can be either comorbid with insomnia or can disturb sleep to create insomnia symptoms.

Untreated sleep problems impact negatively quality of life in these patients. Finding ways to improve our methods of identifying and treating sleep disorders is of essential importance for providers in this field.

2. Prevalence of Insomnia in breast cancer

Complaints of sleep problems are common in breast cancer patients from the time of diagnosis, through treatment and during survivorship. Insomnia is second only to cancer-related fatigue, and was found to occur at clinically diagnosable levels in almost 50% of cancer patients (O. Palesh, et al., 2014), compared to 18% in a general population (O. G. Palesh et al., 2010).

3. Insomnia defined

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (APA, 2013) currently defines insomnia as dissatisfaction with the quality or quantity of sleep that includes difficulty falling asleep, difficulty staying asleep or waking up earlier than planned. Such difficulties occur three or more nights each week despite the opportunity for adequate sleep and result in other distressing symptoms, such as excessive daytime sleepiness and/or daytime fatigue. Diagnostic Criteria for Insomnia (ICSD-3) (Medicine, 2014), similar to the DSM-5 criteria, include difficulty initiating or maintaining sleep, daytime consequences, all of which are not due to an inadequate opportunity for sleep.

4. Associations with insomnia – etiology of insomnia in cancer

The development of insomnia in breast cancer patients and survivors can be explained in relation to the diathesis-stress model (Spielman, Caruso, & Glovinsky, 1987). The model postulates that individual traits (e.g. biological make-up and genetics) interact with their environment, and particular stressors that present themselves, to result in the development in a set of problems or disorders. Not every stressor will result in a significant problem, but those that surpass the threshold of that particular individuals level of reliance or coping, will. A diagnosis of breast cancer, and the events that follow (e.g. treatment, recovery, results), represents a stressor that is challenging to most individuals and problems with sleep becomes one of the common problems as a result.

Spielman applied this model to insomnia and developed the 3P behavioral model, or three-factor/Spielman model (Spielman, Caruso, et al., 1987). The three factor model articulates the three cumulating factors that illustrate the progression from acute and early insomnia to chronic insomnia. The first factor, includes the predisposing or premorbid traits that serve to put some individuals at a greater risk for developing insomnia, such as female gender, increasing age or those who tend to be worriers. The second factor, the precipitating factor, includes events that trigger the onset of sleep difficulties, such as a diagnosis of breast cancer. At this point, many individuals may report experiencing some acute difficulties with sleep. Whether or not those sleep problems become entrained, relates to the perpetuating factors, the final part of the model. Perpetuating factors refer to the set of behaviors that an individual engages in an effort to cope with the sleep problems. Such behaviors include staying in bed longer in hopes of getting more sleep, or staying in bed while awake in hopes that sleep will come. These efforts to compensate for lost sleep are often self-reinforcing in the short term due to occasional benefits, but over time become the habits that ultimately result in a misalignment of sleep ability and sleep opportunity. Behavioral approaches thus tend to focus on creating optimal sleep schedules and behaviors combined with relaxation techniques that focus on decreasing the arousal that often results from the frustration around the perception of “elusive sleep”.

5. Consequences / Sequelae – most concerning / alarming

The range of cancer related treatments, including chemotherapy, radiation, hormonal therapy and surgery have all been found to result in serious side effects (Cleeland et al., 2012).

The range of symptoms experienced by breast cancer patients in both active treatment and survivorship phase that negatively impact their daily quality of life. Fatigue, depression, pain, and hot flashes are some of the most common. Cancer related fatigue is the most reported side effect by both patients and survivors. Between 60-90% of patients describe feeling fatigued at some point during or after treatment and improving sleep alone doesn’t often eliminate complaints of fatigue as it is a symptom with multiple etiologies (Saligan et al., 2015). Depression is also reported in 20-30% of breast cancer patients (Bower, 2008; Reich, Lesur, & Perdrizet-Chevallier, 2008), and combined with symptoms of fatigue, create a perfect storm for sleep problems to develop or worsen.

6. Management of insomnia in cancer

Pharmacotherapy, cognitive-behavioral interventions, complementary and supportive medicine approaches all show some degree of effectiveness in treating the sleep problems observed in cancer patients.  Factors to consider when selecting an approach include scientific evidence, provider comfort and expertise, patient choice, and patient symptom profile.

  • Pharmacological interventions

Pharmacological management of the challenging side effects experienced by patients has been met with mixed results, particularly in the area of sleep problems.  The three most common classes of medications prescribed to breast cancer patient experiencing sleep problems includes non-benzodiazepine hypnotics, benzodiazepines and sedative antidepressants.  Research has found that medications prescribed for sleep, most frequently hypnotics, often help in the short term but rarely address the underlying causes of sleep difficulties.  In particular, the sleep problems that result from behavioral efforts to acquire more sleep, frequently resurface with a vengeance once the sleep medication is stopped.  The behavioral treatment, detailed below, have found equivalent levels of efficacy short term and superior long term results. Recently, in 2016, the American College of Physicians published updated practice guidelines that includes the recommendation that multi-component CBT-I as the first line treatment for insomnia for all patients (Qaseem et al., 2016).  The guidelines emphasize that the use of pharmacological treatments should only be considered for the treatment of insomnia in patients who are, for whatever reason, been unable to participate in CBT-I, as an adjunctive treatment for those with residual symptoms who are receiving, or have received, CBT-I or, in rare cases, as an initial adjunct to those currently starting behavioral treatments in need of a quicker improvement.

  • Behavioral Interventions

Multicomponent CBT-I addresses a combination of both behavioral and cognitive factors that serve to fuel insomnia.  Treatment can be adapted for various patient populations and typically starts with an overview of treatment and sleep education around the mechanisms underlying sleep.  From there, treatment often includes some combination of sleep restriction therapy, stimulus control therapy, relaxation training, cognitive therapy, and sleep hygiene.  CBT-I focuses on developing healthy sleep patterns and behaviors, addressing thought processes that interfere with sleep and giving the patient a set of skills that can be utilized whenever they face a prolonged period of sleep issues.  Ideally, initiating the treatment early on in the treatment process can help the patient throughout all phase of treatment.

Meta-analyses illustrate the effectiveness of CBT-I in the treatment of a range of sleep parameters involved in insomnia in both adult (Geiger-Brown et al., 2015; Trauer, Qian, Doyle, Rajaratnam, & Cunnington, 2015) and breast cancer populations, specifically (Johnson et al., 2016).  CBT-I has been shown to shorten the time it takes to fall asleep, decrease the amount of time spent awake in the middle of the night and increase the amount of time spent asleep relative the time spent in bed.  When comparing CBT-I to pharmacotherapy, a study found that CBT-I had equivalent to superior effects after 6-10 weeks of treatment, with improvements holding steady for many participants at a 3 year follow-up (Mitchell et al, 2012).

Particularly powerful are the two main behavioral components of CBT-I, sleep restriction therapy (Spielman, Saskin, & Thorpy, 1987), which involves limiting the time in bed to the time actually spent sleeping, and stimulus control therapy (Engle-Friedman, Bootzin, Hazlewood, & Tsao, 1992), which involves a set of recommendations aimed at strengthening the association of the bed with sleeping.  As breast cancer patients often report spending more time in bed awake and engaging in other activities, due to pain or fatigue, they begin to associate being in bed with being awake. Specific recommendations often include:

  • Go to bed only when sleepy.
  • Getting out of bed when unable to sleep.
  • Using the bed/bedroom only for sleep and sex (i.e., no reading, watching TV, etc)
  • Arising at the same time every morning.
  • Avoiding naps.

  

For patients that present with intense worry and rumination, along with faulty beliefs and attitudes about sleep, cognitive techniques can be utilized.  The aim of this component is to target faulty underlying beliefs and attitudes about sleep and teach the patient strategies to control their active minds to the extent that they interfere with sleep.  Another useful component to treatment included relaxation training that targets physiological and mental arousal.  Patients can be trained in progressive muscle relaxation, visualization and deep breathing techniques in addition to a meditation practice.  Finally, sleep hygiene ensures that the patient isn’t engaging in sleep interfering behaviors (e.g. caffeine late in the day).  It is important to note that although sleep hygiene alone isn’t effective in isolation from the other elements, it can be useful to make sure that the patient is aware of recommendations related to exercise, caffeine and the optimal sleep environment.

For patients going through cancer treatments, particularly those with time constraints due to managing their treatment and other aspects of their life, Palesh and colleagues modified CBT-I to make it more feasible and acceptable to breast cancer patients receiving treatment.  The resulting intervention Brief Behavioral Therapy for Cancer Related Insomnia (BBT-CI) consists of 2 face to-face sessions and 4 15 minute phone calls and include instructions on: education on sleep specific to breast cancer patients, instructions about bedtime schedule and training in stimulus control, education and restriction on napping and chronorehabilitation techniques (focus on physical activity, sunlight and education on sleep wake cycles and circadian rhythmicity specific to breast cancer).  BBT-CI has been tested in a community setting across 4 sites in the US and showed feasibility and acceptability (O. Palesh et al., resubmitted).  BBT-CI also demonstrated preliminary efficacy on insomnia, health related quality of life, heart rate variability and circadian rhythmicity (O. Palesh, Janelsins, et al., 2017). Additionally, BBT-CI does not require psychologists to administer it; both nurses and clinical research staff were able to successfully deliver all of the components of BBT-CI in the clinics. Larger studies are needed to test the efficacy if this novel intervention.

  • Supportive Medicine Approaches

Supportive medicine approaches are an important adjunct to standard medical treatment of breast cancer that many patients find helpful in managing the side effects that emerge both during and after treatment.  In particular, low to moderate exercise has been shown to be most effective (Schmitz et al., 2010), appears to have positive effects on sleep quality (Sprod et al., 2010), as well as other treatment side effects (O. Palesh, Scheiber, et al., 2017).  Melatonin, as a supplemental substance, has been recommended for sleep (Innominato et al., 2016; Kurdi & Muthukalai, 2016). Other approaches without evidence include relaxation techniques, massage, music therapy, as well as exercise related activities, such as tai chi and yoga (Mustian et al., 2017; Mustian et al., 2010; Mustian et al., 2009). Finally, cancer survivors have also expressed a desire to hear such recommendations from their treatment providers along with getting referrals to an exercise champion, such as an exercise physiologist.

7. Future directions for research and treatment

There are many areas that are ripe for future study.  Incorporation of sleep assessment into the early stages of treatment will allow for early intervention.  Treating acute sleep problems before they become chronic can require less intervention dosage and might improve health related quality of life, adherence to treatment and minimize other prevalent side effects such as depression, cancer-related fatigue and pain. In addition, (O. Palesh et al., 2013) has described the important role of treatment matching of interventions for sleep with cancer-specific care.  For example, BBT-CI may be considerably more useful in early chemotherapy or radiation treatment, sleep aids during acute recovery phases and more comprehensive sleep programs, such as CBT-I during the survivorship phase to assist the patient into developing a long-range set of coping skills to manage a range of potential stressors.

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