Emotion regulation and choice of bilateral mastectomy for the treatment of unilateral breast cancer.

BACKGROUND: There has been steadily increasing use of bilateral mastectomy (BMX) in the treatment of primary breast cancer (BC). In this study, we utilized functional magnetic resonance imaging (fMRI) to examine the influence of emotion regulation on the decision of newly diagnosed BC patients to choose BMX rather than non-BMX treatments. METHODS: We recruited 123 women with unilateral BC, 61 of whom received BMX and 62 of whom received non-BMX treatments, and 39 healthy controls. While participants were in the fMRI scanner, we showed them BC-related and non-BC-negative images. In one condition, they were instructed to watch the images naturally. In another, they were instructed to regulate their negative emotion. We compared the fMRI signal during these conditions throughout the brain. RESULTS: With non-BC-negative images as the baseline, BC patients showed greater self-reported reactivity and neural reactivity to BC-related images in brain regions associated with self-reflection than did controls. Among the BC patients, the BMX group showed weaker activation in prefrontal emotion regulation brain regions during emotion regulation than did the non-BMX group. CONCLUSIONS: BC patients are understandably emotionally hyper-reactive to BC-related stimuli and those who ultimately received BMX experience more difficulty in regulating BC-related negative emotion than non-BMX BC patients. These findings offer neuropsychological evidence that difficulty in managing anxiety related to the possibility of cancer recurrence is a factor in surgical treatment decision-making and may be an intervention target with the goal of strengthening the management of cancer-related anxiety by nonsurgical means. TRIAL REGISTRATION: NCT03050463.

Brief structured respiration practices enhance mood and reduce physiological arousal.

Controlled breathwork practices have emerged as potential tools for stress management and well-being. Here, we report a remote, randomized, controlled study (NCT05304000) of three different daily 5-min breathwork exercises compared with an equivalent period of mindfulness meditation over 1 month. The breathing conditions are (1) cyclic sighing, which emphasizes prolonged exhalations; (2) box breathing, which is equal duration of inhalations, breath retentions, and exhalations; and (3) cyclic hyperventilation with retention, with longer inhalations and shorter exhalations. The primary endpoints are improvement in mood and anxiety as well as reduced physiological arousal (respiratory rate, heart rate, and heart rate variability). Using a mixed-effects model, we show that breathwork, especially the exhale-focused cyclic sighing, produces greater improvement in mood (p < 0.05) and reduction in respiratory rate (p < 0.05) compared with mindfulness meditation. Daily 5-min cyclic sighing has promise as an effective stress management exercise.

Serotonin transporter polymorphism, depressive symptoms, and emotional impulsivity among advanced breast cancer patients.

PURPOSE: This study tested a theory linking a marker of low serotonergic function to both depression and impulsivity in a sample of advanced breast cancer patients, among whom elevated depressive symptoms and difficulty regulating emotions are commonly reported. METHODS: A total of 95 patients provided blood samples for serotonin transporter polymorphic region of the gene (5-HTTLPR) and completed questionnaires that measured depressive symptoms and emotional impulsivity. RESULTS: Structural equation modeling revealed that the s allele of 5-HTTLPR was related to greater depressive symptoms (ß = .20, p < .042) but only marginally to greater emotional impulsivity (ß = .19, p < .068). Depressive symptoms and emotional impulsivity were positively related (ß = .33, p < .003). Further tests explored possible mediation from genotype to one psychological variable via the other. Results suggest that depressive symptoms, particularly perceived interpersonal rejection, may be a pathway linking genotype to emotional impulsivity. CONCLUSIONS: Findings provide the first evidence that low serotonergic function contributes to both depression and impulsivity within a clinically meaningful sample. Furthermore, the link of s allele of 5-HTTLPR to emotional impulsivity was mediated by depressive symptoms, particularly perceptions of social rejection. Findings have implications for advanced breast cancer patients' treatment decision.

Aberrant nocturnal cortisol and disease progression in women with breast cancer.

While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never been unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. Women with ABC (n = 97) and age-matched controls (n = 24) took part in a 24-h intensive physiological monitoring study involving polysomnographic sleep measures and high-density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-h and sleep-associated patterns of plasma cortisol, respectively. The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's > 0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an eightfold increase in the amount of objectively measured wake time (p < 0.004, Wilcoxon Signed-Rank). This cortisol aberration was associated with cancer progression such that the larger the aberration, the shorter the disease-free interval (time from initial diagnosis to metastasis; r = -0.30, p = 0.004; linear regression). The same aberrant spike was present in a similar percent of women without ABC and associated with concomitant sleep disruption. A greater understanding of this sleep-related cortisol abnormality, possibly a vulnerability trait, is likely important in our understanding of individual variation in the progression of cancer.

Correspondence of plasma and salivary cortisol patterns in women with breast cancer.

INTRODUCTION: The 'diurnal slope' of salivary cortisol has been used as a measure of stress and circadian function in a variety of reports with several detailing its association with cancer progression. The relationship of this slope, typically a negative value from high morning concentrations to low evening concentrations, to the underlying daily variation in total plasma cortisol throughout the 24-hour cycle, however, has never been reported. METHODS: To examine the relationship between the diurnal salivary cortisol slope and the underlying pattern of plasma cortisol in individuals with cancer, we examined a cohort of women with advanced breast cancer (n = 97) who had saliva and plasma collected during a modified 24-hour, constant posture protocol. RESULTS: We found that the steepness of the diurnal slope of salivary cortisol was correlated with the amplitude of plasma cortisol rhythm when the slope was calculated from samples taken at wake + 30 min and 9 PM (r = -0.29, p > 0.05). Other variants of salivary slope calculations were not significantly correlated with the amplitude of the plasma cortisol rhythm. Diurnal salivary cortisol slope steepness was not correlated with the time between habitual waking and the computed circadian peak of cortisol, but there was a correlation between diurnal slope steepness and the time between habitual waking and the time of the awakening spike of morning cortisol (r values <-0.23, p values <0.05). CONCLUSION: It therefore appears that in women with advanced breast cancer, diurnal salivary cortisol slope primarily represents aspects of the cortisol awakening response in relation to evening levels more than the circadian rhythm of total plasma cortisol.

Actigraphy-measured sleep disruption as a predictor of survival among women with advanced breast cancer.

BACKGROUND: Poor sleep, prevalent among cancer survivors, is associated with disrupted hormonal circadian rhythms and poor quality of life. Using a prospective research design, this study aimed to clarify the relationship between objective measures of sleep efficiency and sleep disruption with survival among women with advanced breast cancer. METHOD: We examined sleep quality and duration via wrist-worn actigraphy and sleep diaries for 3 days among 97 women in whom advanced breast cancer was diagnosed (age = 54.6 ± 9.8 years). Sleep efficiency was operationalized using actigraphy as the ratio of total sleep time to total sleep time plus wake after sleep onset. RESULTS: As hypothesized, better sleep efficiency was found to predict a significant reduction in overall mortality (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.98; P < 0.001) at median 6 y follow-up. This relationship remained significant (HR, 0.94; 95% CI, 0.91-0.97; P < 0.001) even after adjusting for other known prognostic factors (age, estrogen receptor status, cancer treatment, metastatic spread, cortisol levels, and depression). Secondary hypotheses were also supported (after adjusting for baseline prognostic factors) showing that less wake after sleep onset (HR, 0.41; 95% CI, 0.25-0.67; P < 0.001), fewer wake episodes, (HR, 0.93; 95% CI, 0.88-0.98; P = 0.007); and shorter wake episode duration (HR, 0.29; 95% CI, 0.14-0.58; P < 0.001) also contributed to reductions in overall mortality. CONCLUSIONS: These findings show that better sleep efficiency and less sleep disruption are significant independent prognostic factors in women with advanced breast cancer. Further research is needed to determine whether treating sleep disruption with cognitive behavioral and/or pharmacologic therapy could improve survival in women with advanced breast cancer.

Bedtime misalignment and progression of breast cancer.

Disruption of circadian rhythms, which frequently occurs during night shift work, may be associated with cancer progression. The effect of chronotype (preference for behaviors such as sleep, work, or exercise to occur at particular times of day, with an associated difference in circadian physiology) and alignment of bedtime (preferred vs. habitual), however, have not yet been studied in the context of cancer progression in women with breast cancer. Chronotype and alignment of actual bedtime with preferred chronotype were examined using the Morningness-Eveningness Scale (MEQ) and sleep-wake log among 85 women with metastatic breast cancer. Their association with disease-free interval (DFI) was retrospectively examined using the Cox proportional hazards model. Median DFI was 81.9 months for women with aligned bedtimes ("going to bed at preferred bedtime") (n = 72), and 46.9 months for women with misaligned bedtimes ("going to bed later or earlier than the preferred bedtime") (n = 13) (log rank p = 0.001). In a multivariate Cox proportional hazard model, after controlling for other significant predictors of DFI, including chronotype (morning type/longer DFI; HR = 0.539, 95% CI = 0.320-0.906, p = 0.021), estrogen receptor (ER) status at initial diagnosis (negative/shorter DFI; HR = 2.169, 95% CI = 1.124-4.187, p = 0.028) and level of natural-killer cell count (lower levels/shorter DFI; HR = 1.641, 95% CI = 1.000-2.695, p = 0.050), misaligned bedtimes was associated with shorter DFI, compared to aligned bedtimes (HR = 3.180, 95% CI = 1.327-7.616, p = 0.018). Our data indicate that a misalignment of bedtime on a daily basis, an indication of circadian disruption, is associated with more rapid breast cancer progression as measured by DFI. Considering the limitations of small sample size and study design, a prospective study with a larger sample is necessary to explore their causal relationship and underlying mechanisms.

Psychosocial correlates of sleep quality and architecture in women with metastatic breast cancer.

BACKGROUND: Sleep disturbance is prevalent among women with metastatic breast cancer (MBC). Our study examined the relationship of depression and marital status to sleep assessed over three nights of polysomnography (PSG). METHODS: Women with MBC (N=103) were recruited; they were predominately white (88.2%) and 57.8±7.7 years of age. Linear regression analyses assessed relationships among depression, marital status, and sleep parameters. RESULTS: Women with MBC who reported more depressive symptoms had lighter sleep (e.g., stage 1 sleep; P<.05), less slow-wave sleep (SWS) (P<.05), and less rapid eye movement (REM) sleep (P<.05). Single women had less total sleep time (TST) (P<.01), more wake after sleep onset (WASO) (P<.05), worse sleep efficiency (SE) (P<.05), lighter sleep (e.g., stage 1; P<.05), and less REM sleep (P<.05) than married women. Significant interactions indicated that depressed and single women had worse sleep quality than partnered women or those who were not depressed. CONCLUSION: Women with MBC and greater symptoms of depression had increased light sleep and reduced SWS and REM sleep, and single women had worse sleep quality and greater light sleep than married counterparts. Marriage was related to improved sleep for women with more depressive symptoms.

Exploring Emotion-Regulation and Autonomic Physiology in Metastatic Breast Cancer Patients: Repression, Suppression, and Restraint of Hostility.

We examined relationships between three emotion-regulation constructs and autonomic physiology in metastatic breast cancer patients (N = 31). Autonomic measures are not often studied in breast cancer patients and may provide evidence of an increase in allostatic load. Patients included participated as part of a larger clinical trial of supportive-expressive group therapy. Systolic and diastolic blood pressure and heart rate were assessed at a semi-annual follow-up. We averaged 3 resting assessments and used measures of Repression, Suppression, Restraint of Hostility, and Body Mass Index as predictors of autonomic response. We found that higher repression was significantly associated with higher diastolic blood pressure, while higher restraint of hostility was significantly associated with higher systolic blood pressure. A repressive emotion regulation style may be a risk factor for higher sympathetic activation possibly increasing allostatic load, while restraint of hostility may be a protective factor for women with metastatic breast cancer.

Sleep disturbances in women with metastatic breast cancer.

We examined sleeping problems in women with metastatic breast cancer in relation to depression, social support, and salivary cortisol. Ninety-seven women with metastatic breast cancer were drawn from a larger study on the effects of group therapy on quality of life and survival. This study is based on the baseline assessments conducted prior to randomization into treatment conditions. Sleep, depression symptoms, and social support were assessed by self-reporting. Cortisol was assessed from saliva samples taken over a 3-day period. Medical status and demographic characteristics were also examined in relation to each sleep variable in multiple regression analysis. Most women (63%) reported one or more types of sleep disturbance and 37% reported using sleeping pills in the previous 30 days. Problems with falling to sleep were significantly related to greater pain and depressive symptoms. Problems of waking during the night were significantly associated with greater depression and less education. Problems in waking/getting up were significantly associated with greater depressive symptoms and less social support. Sleepiness during the day was not significantly related to the variables in the regression model. Fewer hours of sleep were significantly associated with metastases to the bone, higher depressive symptoms, and more social support. Women who reported sleeping 9 or more hours per night, compared to those who reported a moderate amount of sleep (6.5-8.5 hours), had significantly lower 9 p.m. cortisol levels. Use of sleeping pills was more frequent among women reporting greater pain and depressive symptoms. These results suggest that women with metastatic breast cancer who are at higher risk for having sleeping problems are those who are less educated, in pain, depressed, have bony metastases, or lack social support.