Sleep Quality in Women with Breast Cancer: An Integrative Review

Conclusions: Sleep disruptions are associated with breast cancer in woman, and affects their overall health. It is essential for nurses to identify sleep disorders and their impact on the health and quality of life of women with breast cancer. A deeper understanding of sleep quality in women with breast cancer can increase cancer nurses’ skill in caring for their patients. Sleep Quality in Women with Breast Cancer: an Integrative Review REVIEW Thalyta Cristina Mansano-Schlosser1, Maria Filomena Ceolim1, Teresa D Valerio2


Introduction and Background
It is estimated that until 2020, the number of new cases of cancer per year will be about 15 million, of which about 60 % will occur in developing countries. [1] Breast cancer is the second most frequent type of cancer in the world, and the most common cancer in women [1]. During 2010, in the United States, over 207,000 women were diagnosed with breast cancer [2].
Sleep disturbances occur in all types of cancer patients, and are associated with multiple factors such as depression, anxiety, treatment (e.g., chemotherapy radiation and surgery), cancer treatment-induced hot flashes, pain, fatigue and changes in biological rhythms [3]. Most studies do not consider whether sleep changes are associated with baseline sleep quality, baseline mental and physical health, demographic and clinical variables. Such associations might lead clinicians to target those at high risk for sleep problems [4].
An important study showed that better sleep efficiency was found to predict a significant reduction in overall mortality [5]. Additional research is needed to determine if beginning treatment of these symptoms before the start of chemotherapy will minimize symptom severity over time [6].
Sleep problems occur in many patients with cancer resulting in sleep deprivation that may affect their immunological status. Sleep deprivation produces a stress reaction in the body, being immunologically best characterized as an increase in leukocyte and neutrophil count, and in serum C-reactive protein rates. An experimental study conducted with healthy subjects showed that a single night of sleep deprivation is sufficient to cause these increases that return to baseline only with ten hours of recovery sleep. Cancer patients experiencing chronic sleep loss may be more vulnerable to these immunological changes because of the obstacles in obtaining sufficient recovery sleep, thus mounting an exacerbated and sustained inflammatory response [7].
Furthermore, Liu et al [8] reports a longitudinal relationship between fatigue, sleep parameters, and inflammation in breast cancer patients. These authors found that changes in reports of sleep quality were significantly associated with a decrease in circulating levels of IL-1RA. Additionally, there are changes in fatigue and sleep quality that were sig-nificantly associated with an increase in circulating levels of IL-6, and the relationship between sleep quality and IL-6 was likely driven by fatigue.
When sleep disturbances become chronic, nurses need to make recommendations and referrals [9]. Because the sleep disturbances are common among breast cancer survivors, even after completion of active cancer treatment [10].
In a study aimed to associate breast cancer symptoms with sleep quality, [11] researchers found poor sleep quality present in 85% of women. A followup of those women, 2 to 7 months after baseline, revealed that 20% of those who reported poor sleep quality had worsening of clinical symptoms and 8% died [11,7] The recognition that poor sleep quality may represent a prognostic factor in cancer patients should encourage nurses and other health professionals to give special attention to this important aspect of routine life [4,12]

Review Questions
The purpose of this review is to evaluate the scientific literature on sleep quality in women with breast cancer, and to assist nurses with understanding the potential health effect of poor sleep quality. The review questions are: 1) How is the sleep quality in women with breast cancer? 2) What health issues are associate with poor sleep quality in women with breast cancer?

Search Criteria
The population of concern is women (18 years or older), diagnosed with any type of breast cancer, and who are undergoing any treatment. Additional inclusion criteria are full-text articles, published in the last eight years (2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016), and in English. The primary outcome measure of interest is sleep quality including sleep, sleep duration, sleep disturbance, insomnia, and circadian-rhythms. This review con-siders both experimental and epidemiological study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies.

Search Strategy
An initial search of PubMed, CINAHL, PsycINFO, Cochrane database of systematic reviews and Joanna Briggs databases was undertaken. The title, abstract, and keywords of the articles were reviewed for relevance to the inclusion criteria. Data collection was performed utilizing an instrument to identify the publication (main authors, year of publication), research purpose, methodological characteristics (design, sample, and instruments), and findings with conclusions on sleep quality and associated health issues.

Results
We selected 27 studies for review from an initial search in which 634 articles were found as outlined in the Figure 1.
Of the 634 articles found in the databases searched, we retrieved 27 articles that met the inclusion criteria as outlined in the Table 1.
Levels of Evidence by the Joanna Briggs Institute (JBI) Levels of Evidence and Grades of Recommendation Working on Table 2. [13].  Compared to NC, BC had longer NAPTIME, worse sleep quality, more fatigue, more depressive symptoms, more disrupted CARs and worse QoL at Baseline Cycle-4, BC showed worse sleep, increased fatigue, more depressive symptoms, and more disrupted CARs compared to their own Baseline levels and to NC (all p's<0.05). By 1-year, BC's fatigue, depressive symptoms and QoL returned to Baseline levels but were still worse than those of NC, while NAPTIME and CARs did not differ from NC's Additional research is needed to determine if beginning treatment of these symptoms before the start of chemotherapy will minimize symptom severity over time. At baseline, 52% of participants reported poor sleep in the month prior to enrollment. Compared to subjects on placebo, subjects randomized to melatonin experienced significantly greater improvements in subjective sleep quality as measured by the PSQI, including domains on sleep quality, daytime dysfunction and total score. Sleep disturbances are common among breast cancer survivors, even after completion of active cancer treatment. This is the first randomized placebo-controlled study among breast cancer survivors to demonstrate that melatonin was associated with an improvement in subjective sleep quality, without any significant adverse effects. The results showed that disturbed sleep (PSQI score ≥5) prior to CT infusion was associated with greater fatigue, and more negative and anxious mood throughout the 3 week CT cycle, and good pre-CT infusion sleep (PSQI score <5) buffered anxious mood in the first days following infusion.
No evening symptom or mood ratings were related to subsequent sleep quality. These findings suggest that disturbed sleep before and after a CT infusion exacerbates fatigue, and negative, anxious, and drowsy mood during a CT cycle. Reducing sleep disturbance may be an important way to improve quality of life during chemotherapy. tance of longitudinal studies because analyzing the patient in 2 or more stages of treatment and documenting the difference in quality of sleep, may be helpful to nurses in managing their patients care. Nine articles reported randomized clinical trials [8,10,[16][17][18][19][20][21]] and 3 were a secondary analysis [4,[22][23].

How Is the Sleep Quality in Women with Breast Cancer?
All 27 studies in this review found a significant level of sleep disturbance in women with breast cancer at various stages in their treatment. A summary of the findings is in Table 1.
Common sleep-time complaints noted in all of these studies is time spent in bed without sleeping, difficulty returning to sleep, decreased nocturnal sleep duration, increased sleep latency and waking earlier than desired. Additionally, the associated wake-time symptoms of sleepiness, fatigue, increased naps, cognitive impairment, and performance are also prevalent.
Mosher and Duhamel report that 70% of the patients completing the PSQI had scores greater than the cutoff point of five, indicating significant decrements in sleep quality [28]. In a longitudinal study, more than 85% of the patients had a high number of nighttime awakenings [16]. When comparing wo- men with cancer-related fatigue and postmenopausal women without cancer, the authors found that breast cancer patients showed significantly more sleep difficulties [27]. These sleep problems were characterized by prolonged sleep onset latency (M= 54.3, SD= 49.2 minutes) and frequent nighttime awakenings, despite 40% of the patients using sleep medications three or more times a week [16]. Greater ongoing fatigue or sleep disturbance predicted a slower cortisol decline, and longer sleep latency predicted both a greater cortisol linear decline and slower cortisol decline [9]. Several studies elucidate how the sleep quality changed during cancer treatments such as chemotherapy or radiotherapy. Considering the PSQI score >5 that represents poor quality sleep, [29] found that 65% of women self-reported poor sleep in the month preceding chemotherapy. Subjective sleep quality was poor at baseline and remained unchanged throughout treatment [3]. Half of the survivors reported no sleep duration change over time; however, 25% reported sleep changes indicating a temporary (5.6%), late-occurring (14%), or sustained (5.9%) change [15]. Patients reported poor quality of life and poor sleep quality before and during chemotherapy with short sleep time and long naps recorded at both time points [26].
Prior to chemotherapy, participants' related mild fatigue, and poor sleep quality; after an intervention using behavior therapy, they perceived increased sleep quality [27]. On Cycle-4 chemotherapy, the breast cancer patients showed worse sleep, increased fatigue and more depressive symptoms, compared to their baseline levels [6].
A study suggests that disturbed sleep before and after a chemotherapy infusion exacerbates fatigue and anxiety [30]. Authors concluded that reducing sleep disturbance may be an important way to improve quality of life during chemotherapy [30].
Other studies reported using an intervention and the authors concluded that future work might consider integrating sleep and fatigue content into stress management interventions for women with early-stage breast cancer [20]. Compared to usual care, eletro acupuncture produced significant improvement in fatigue, anxiety and depression [21]. The cognitive behavioral therapy for insomnia was used and showed durable improvements in insomnia and sleep quality [19].
A few researchers compare the sleep quality in those with breast cancer to other types of cancer. For instance, 2 articles compare women with breast cancer (BC) and men with prostate cancer (PC). Both BC and PC patients report the most sleep problems prior to and during chemotherapy. [14] The occurrence rates for sleep disturbance and fatigue were significantly higher in patients with breast cancer as compared to prostate cancer [2].
Future work may consider integrating sleep and fatigue content into stress management interventions for women with early-stage breast cancer [20].

What Health Issues Are Associated with Poor Quality Sleep in Women with Breast Cancer?
Poor sleep quality is reported in all 27 studies and is associated with several health issues such as severe fatigue, depression, anxiety, hot flashes, pain, and generally poorer quality of life. A significant relationship between fatigue and sleep disturbances was found in 3 studies [2,3,9,2,3,28,30] and higher scores on the PSQI predicted membership in the higher fatigue group for general and physical fatigue. [31] Participants with breast cancer self-reported significantly higher levels of sleep disturbance (P=.008) and fatigue (P=.005) than patients with prostate cancer [2]. Fatigue was significantly associated with subjective reports of poor sleep and objective measures of daytime sleepiness; however, not with nocturnal sleep as measured by actigraphy [3]. Additionally, there is a high prevalence of distress, sleep problems, and fatigue across demographic and medical subgroups of metastatic breast cancer patients [28].
The relationship between fatigue and sleep has been reported in other studies [12,32]. Fatigue was significantly correlated with subjective and objective measures of sleep in women with breast cancer [8]. Women with insomnia also reported significantly higher levels of depression, anxiety and fatigue [33].
Studies identify a significant relationship between sleep quality and mental health disorders including depression and anxiety [21,22,[24][25]34]. One group of researchers that investigated if breast cancer survivors (BCS) with insomnia can be grouped according to their level of fatigue discovered significant differences in insomnia severity, anxiety, depression, and quality of life among the subgroups of exhausted, tired and restored [22].A study of prevalence, severity, and correlates of sleep-wake disturbances compares long-term breast cancer survivors (BCS) to age-matched women without breast cancer (WWC) and finds significant correlates of prevalence with poor sleep for BCS including hot flashes, poor physical functioning, depressive symptoms and distress [24].
The authors identify that comorbidity, evening fatigue, and depressive symptoms predicted baseline levels of subjective sleep disturbance, and that depressive symptoms predicted the trajectory of subjective sleep disturbance [25]. Worse Physical Component scores were associated with reports of poor sleep and less recorded nap time, suggesting sleep plays an important role in cancer patients' quality of life [8].

Discussion
Our review findings expose the overlooked disorders of sleep in women with breast cancer and the associations with cancer-related fatigue (CRF), depression and other important health issues. Furthermore, these 27 studies consistently document the high prevalence of poor sleep quality and decrease in quality-of-life. To begin to address this important patient care issue, we recommend use of tools like the PSQI, actigraphy and sleep diary for identification and assessment of sleep quality in women with breast cancer.
Comparisons between women with and without cancer revealed that breast cancer survivors had significantly higher PSQI global scores, indicating poorer sleep quality, as compared to women without breast cancer [24]. Another study comparing 30 fatigued female breast cancer chemotherapy outpatients and 32 non-cancer postmenopausal fatigued patients found a significantly longer sleep latency in the breast cancer group. Forty-seven percent of CRF patients expressed "severe difficulty" with sleep latency, while 25% of postmenopausal women were in this category [16]. Additionally, women's menopausal status when starting chemotherapy was associated with differing patterns of sleep and hot flashes over time [4].
The grouping or "clustering" of cancer-related symptoms has been highlighted in recent reports as an important priority for nursing research. Greater knowledge is needed regarding the interaction of multiple symptoms and their potential impact on cancer patient outcomes if advances are to be realized in caring for persons diagnosed with cancer. The studies in this review inform health care professionals to proactively assess for the continued presence of multiple symptoms once treatment has ended, with an understanding that a single, intense symptom rarely occurs. Moreover, the focus of care should target the symptom interactions, and their association with quality of life. Those caring for cancer patients need to overcome the outdated practice of managing pain, fatigue, depression or poor sleep quality as isolated symptoms by concurrently assessing and managing these related health problems [12,22]. Tools such as PSQI, actigraphy and sleep diary can assist health professionals to assess the sleep quality of their female breast cancer patients.
The PSQI is a patient questionnaire designed to evaluate the subjective sleep quality and disturbances that have been present during the past month. This questionnaire, which has been validated in several countries and languages, contains 19 items that can be self-administered or employed in an interview, and 5 questions to be answered by roommates. The latter 5 questions are used only for information and are not scored. The 19 questions are grouped into seven sleeprelated components comprising quality, latency, duration, efficiency, disturbances, use of sleeping medication, and daytime sleepiness. The score of each component ranges from zero to three points. The overall score is obtained with the sum of components, ranging from zero to 21points. The higher the value obtained, the poorer sleep quality with the overall score of five points as the cut off for distinguishing between poor sleep quality (higher than five points) from good sleep quality (five points or less) [29].
Actigraphy is a technique for recording a persons' sleep-wake pattern through recording of limb movements for a 24-hour cycle. This device is placed on the wrist of the non-dominant limb and detects motion, thus recording rest and activity. It provides data for interpretation in order to infer the presence of sleep or wakefulness. Frequent movements are interpreted as wakefulness, and low movements as sleep. It provides data on total sleep time, total time awake, number of awakenings, and sleep latency [35,36]. This objective measure records sleep and awake patterns. This tool is helpful to the health care professional as an adjunct to the PSQI and sleep diary; although, not commonly found in use outside of a sleep disorders center.
Another means of assessing sleep patterns and sleep quality is a sleep diary, which is often used with actigraphy. This diary is usually completed for 14 days by the patient to document sleep patterns, subjective sleep of quality and behaviors affecting sleep [8]. documented that this tool could be used to obtain reliable data about home sleep/wake patterns in women undergoing chemotherapy for breast cancer.
Studies in this review consistently found that poor sleep quality is experienced by female breast cancer patients. Nurses assess the responses that patients have to disease in order to select and implement interventions to improve their quality of life. Because poor sleep quality is a frequent complaint of women with breast cancer and decreases their quality of life, it is essential to routinely assess for sleep disruptions and intervene. The nurses' evaluation of sleep quality should include the associated symptoms discovered in these studies that may be clustered with pain, fatigue, depression and others. And just one base population study was found on this study, it is necessary more future studies [37].
The sleep disturbances often become chronic and nurses need to make recommendations and to treat them because sleep disturbances are common among breast cancer survivors, even after completion of active cancer treatment, we need to be proactive to avoid the worst problems after treatment [10].
Interventions studies are very important and authors concluded MBSR may be an efficacious treatment to improve objective and subjective sleep parameters in breast câncer patients [17]. In another study, when compared with controls, the intervention group demonstrated a significant increase in sleep duration with MBSR [18].
However, it is important to note that often the poor quality of sleep gets little attention from patients, who regard it as a "normal" consequence of the treatment. Despite the latest knowledge on this topic, many health care professionals do not identify and treat their patients' sleep problems. If untreated, many sleep disorders can become chronic health problems in patients with cancer, persisting after treatment of the disease. Furthermore, attention should be paid to the importance of quality-of-life that has been frequently explored in the literature and encompasses sleep.

Limitations
There is a possibility that relevant articles were missed by this review. Future reviews are necessary to expand knowledge about the relationships between sleep quality, fatigue, depression, and pain in women with breast cancer.

Implications for Practice
An important aspect of nursing care for breast cancer patients is assessment for associated health problems, which includes sleep quality. We recommend the use of validated screening tools such as the PSQI and sleep diary to assess for sleep disturbances. This assessment should be done at several key points in the cancer care process including the initial encounter prior to diagnosis, at diagnosis, during treatment, at the end of treatment, and at follow-up.
Furthermore, we recommend that nurses increase their knowledge of normal and abnormal sleep to better assess for disorders, counsel their patients, and refer for further evaluation and management. Through regular assessment of sleep quality, nurses can promote additional improvements in the quality-of-life for cancer patients.

Conclusions
This review is relevant in view of the increased incidence of breast cancer and the high prevalence of sleep disorders Assessing and identifying sleep problems in cancer patients should be a priority, as the disease is debilitating, and compromised sleep quality may further decrease functional ability. The negative effects of poor sleep quality can exacerbate other cancer-related symptoms and persist long after the end of treatment. We recommend that researchers focusing on breast cancer care should study the effectiveness of interventions that target the symptom cluster of poor sleep quality, pain, fatigue, and depression to decrease the burden of this devastating disease.