Insomnia is unfortunately one of many factors that worsen the quality of life of cancer patients, and numerous studies have documented its high frequency. Insomnia symptoms have been described in nearly half the patients who have received a recent cancer diagnosis. Severe sleep difficulties have been reported by a wide range from 25 to 59% of cancer patients, double the rate described in the general population [1]. A recent systematic review of sleep disturbances and/or sleep disorders in cancer found a prevalence up to 95% in these patients [2]. Differences in the observed rates may depend on heterogeneity in the definition and measurement of insomnia symptoms [3]. Studies using objective measurements of sleep quality in cancer patients are scarce, but actigraphic measurements of sleep outcomes in cancer patients undergoing chemotherapy show an aggravation of sleep disturbances with continuation of the chemotherapy regimen through several series [4]. A recent study reported the presence of clinically significant sleep difficulties in 64% of patients with cancer, even though only a small portion of them mentioned such disorders as their first concerns in their integrative oncology consultation [5]. Despite the frequency of insomnia in cancer patients, its consequences on daytime functioning and health are often overlooked. Studies focus on the various stages of the disease by evaluating the consequences of diagnosis and therapy on sleep, also assessing the consequences on sleep quality after a survival period of months or years. Some authors focused on objective measurements (through actigraphy and polysomnography) of sleep quality in breast cancer patients before the start of chemotherapy, describing disturbed sleep and fatigue prior to the treatment and suggesting a role for early intervention [6]. Insomnia symptoms were also investigated during the chemotherapy treatment, noting that, on the seventh day following the first chemotherapy cycle, 36.6% of patients reported insomnia symptoms, and 43% met the diagnostic criteria for insomnia syndrome, a number three times higher than in the general population [7]. An 18-month longitudinal study on 856 patients with heterogeneous cancer sites and stages showed a general decline of the prevalence of insomnia, even though its rates were still considerable at the end of the study [8]. Finally, daytime sleepiness and sleep duration were investigated in long-term cancer survivors. While no association was found between a history of cancer and sleep duration, daytime sleepiness was found to persist in individuals diagnosed more than two years earlier [9]. Another study focused on 1–10-year breast cancer survivors describing severe subjective insomnia [10]. Concerning the cancer site, breast, gynaecologic, and lung cancers appear to result in the highest risk of developing insomnia symptoms ^[7][10][11][7,10,11], while lower rates were found in men with prostate cancer [8]. Among all cancer sites, breast cancer has the highest prevalence of insomnia symptoms ^{[6][7][11][12]}[6,7,11,12], and most studies on disturbed sleep in cancer patients focus on women with breast cancer ^[13][14][15][13,14,15]. This prevalence could be linked to several causes: nocturnal awakenings are related to the hot flashes caused by treatment ^[16][17][16,17], and, as also mentioned for other cancer sites, pain and stress ^[18][19][18,19] play a major role.

The causes and effects of insomnia in cancer patients may have a mutual causal relationship. Psychiatric diseases, particularly anxiety and depressive disorders, are frequent comorbidities in cancer patients ^[13][20][21][13,20,21]. Insomnia is a frequently present symptom for both these disorders. Demoralisation, often presented by cancer patients, may accompany mood disorders and has been linked to increased sleep difficulties in breast cancer patients ^[22][23][24][22,23,24]. However, it is unlikely that the high prevalence of insomnia symptoms in cancer patients is exclusively related to psychiatric symptoms [1]. During this challenging pandemic period, the prevalence rates of psychiatric symptoms and insomnia are significantly raised [25], and we may expect negative consequences, especially in cancer patients, who may find it more difficult to access care services and cancer treatments. Stress-related cancer diagnosis (Distress) is associated with hyperarousal, a state of increased somatic, cortical, and cognitive activation, and some data have shown increased cortisol levels, body temperature, 24-h metabolic rate, and heart rate in cancer patients with insomnia symptoms. In addition, pain provoked by the disease or its surgical or pharmacological treatment may easily impact sleep quality ^[2][26][2,26]. Pain is, in fact, one of the most disabling symptoms for the cancer patient, affecting more than 50% of patients at any stage of the disease and more than two-thirds of those with metastatic or advanced disease [27]. Numerous studies have revealed that people with severe or chronic pain have a higher prevalence of depressive symptoms and insomnia [2]. In addition, the close relationship between pain and depression may also play a reciprocal role in amplifying the effects on insomnia. The pain–depression binomial would seem to have a dual reinforcing mechanism as its core. On the one hand, untreated pain is linked to a decline in psychological defence mechanisms, predisposing patients toward the emergence of psychological disorders. On the other hand, depressive symptoms may increase sensitivity and perception of pain, lowering the threshold and amplifying sufferance [28].

Moreover, as many treatments prescribed for noncancer patients can result in sleep disturbances [29], this is also true for anticancer drugs. Treatments can be a cause of sleep disturbances either for the provoked emotional distress or for their direct side effects. Breast cancer patients and survivors are prone to have insomnia caused by the aforementioned hot flashes but also by the consequences of chemotherapy, radiotherapy therapy, and hormone therapy ^{[1][17][30][31]}[1,17,30,31]. Indeed, radiotherapy and chemotherapy (this one in particular) have been associated with sleep disturbances. Multiple side effects of these treatments may worsen insomnia symptoms. The main cause could be reported by the impact of these agents on body functions and effects such as pain, diarrhoea, nausea, and vomiting [31]. Glucocorticoids, often prescribed in the supportive care of cancer patients, could result in an alteration of the sleep–wake cycle through disruption of the cortisol rhythm [32].

One study focused on the molecular mechanisms associated with sleep disruption in cancer patients, suggesting a reciprocal causative approach, a “‘chicken or the egg’ phenomenon”, where poor sleep takes a role in tumorigenesis and cancer progression [33]. These findings are consistent with recent studies suggesting that chronic circadian disruption (caused, for example, by a job requiring night shifts) has a causative effect on the pathophysiology of breast cancer and its metastatic dissemination [34]. Moreover, sleep efficiency as measured by actigraphy is related to prognostic outcomes in patients with advanced breast cancer [35]. Studies investigating how insomnia symptoms may be both a risk factor and a consequence of cancer, focusing on many different cancer sites, have been described in a recent comprehensive review [36]. Many authors refer to a behavioural model for sleep disturbances called the “3-P’s Model”, first described in 1987 ^[37][38][37,38], which describes the different causes as consisting of three groups: predisposing, precipitating, and perpetuating factors. While predisposing factors are represented by sex (women tend to have more sleep disturbances than men), anxiety traits, or the presence of a psychiatric disorder and a family or personal history of insomnia, precipitating factors are more related to the consequences of cancer and its treatments, such as pain and side effects of drugs and surgery. Finally, perpetuating factors involve maladaptive sleep behaviours as a shifting sleep phase or spending more time in bed or, for example, not following sleep hygiene recommendations ^{[9][30][39][40][41][42][43]}[9,30,39,40,41,42,43]. Investigating and treating insomnia symptoms in cancer patients is critical, especially considering their comorbidity with fatigue, a frequent consequence of cancer and cancer treatments. When approaching a patient reporting cancer-related fatigue or excessive daytime sleepiness (EDS) [44], its relationship with cancer-related sleep disorders should be appropriately evaluated ^[11][45][11,45]. Along with and before the pharmacological approach to insomnia symptoms, nonpharmacological treatment should be considered by the clinician. First, sleep hygiene is an important tool for the treatment of insomnia in cancer patients, who tend to spend more time in bed during the day, with consequences on the sleep–wake schedule caused by frequent naps [1]. Therefore, a sleep diary and sleep hygiene education can be useful tools for the initial approach to insomnia symptoms in cancer patients, as in the general population. The American Sleep Association has listed some basic tips for improving sleep quality, including going to bed at a regular time; avoiding naps during the day; leaving the bed if not asleep after 5–10 min; avoiding watching TV or reading in bed; avoiding caffeinated beverages in the afternoon; avoiding smoking, alcohol, and over-the-counter sleep medication; exercising daily but not before bedtime; and, finally, having a quiet, comfortable room and a prebedtime routine [46]. A combination of pharmacological and nonpharmacological treatments could be a useful strategy to “break the vicious cycle of fatigue and insomnia” often presented by cancer patients [26]. Nonpharmacologic treatments such as CBT have been shown to be an effective approach, but their description is beyond the scope of this study. If it is ultimately decided to prescribe drug therapy for the treatment of insomnia in a cancer patient, many considerations are necessary. These include hepatic metabolism and the resulting pharmacokinetic interactions. A classic example of a pharmacokinetic interaction between psychiatric drugs and chemotherapeutics is the effect that SSRIs have on cytochrome CYP2D6 and the consequences for tamoxifen metabolism, reducing its clinical benefits [47]. These interactions may concern the relationship between other psychotropic drugs and chemotherapeutic agents ^[48][49][48,49].