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Although fear of recurrence (FCR) is common among cancer survivors, it remains unclear what factors predict initial levels (e.g., prior to surgery) or changes in FCR in the post-treatment period. Among women treated for breast cancer, this study evaluated the effects of demographic, clinical, symptom, and psychosocial adjustment characteristics on the initial (preoperative) levels of FCR and trajectories of FCR over 6 months following surgery. Prior to and for 6 months following breast cancer surgery, 396 women were assessed for demographic and clinical (disease and treatment) characteristics, symptoms, psychological adjustment characteristics, and quality of life (QOL). FCR was assessed using a four-item subscale from the QOL instrument. Hierarchical linear modeling was used to examine changes in FCR scores and to identify predictors of inter-individual differences in preoperative FCR levels and trajectories over 6 months. From before surgery to 6 months post-operatively, women with breast cancer showed a high degree of inter-individual variability in FCR. Preoperatively, women who lived with someone, experienced greater changes in spiritual life, had higher state anxiety, had more difficulty coping, or experienced more distress due to diagnosis or distress to family members reported higher FCR scores. Patients who reported better overall physical health and higher FCR scores at enrollment demonstrated a steeper decrease in FCR scores over time. These findings highlight inter-individual heterogeneity in initial levels and changes in FCR over time among women undergoing breast cancer surgery. Further work is needed to identify and provide interventions for women experiencing FCR during and after breast cancer treatment.

UnlabelledPersistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N=398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility.PerspectiveFor persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women.

Context Oncology patients with persistent pain treated in outpatient settings and their family caregivers have significant responsibility for managing pain medications. However, little is known about their practical day-to-day experiences with pain medication management. Objectives The aim was to describe day-to-day pain medication management from the perspectives of oncology outpatients and their family caregivers who participated in a randomized clinical trial of a psychoeducational intervention called the Pro-Self© Plus Pain Control Program. In this article, we focus on pain medication management by patients and family caregivers in the context of multiple complex health systems. Methods We qualitatively analyzed audio-recorded intervention sessions that included extensive dialogue between patients, family caregivers, and nurses about pain medication management during the 10-week intervention. Results The health systems context for pain medication management included multiple complex systems for clinical care, reimbursement, and regulation of analgesic prescriptions. Pain medication management processes particularly relevant to this context were getting prescriptions and obtaining medications. Responsibilities that fell primarily to patients and family caregivers included facilitating communication and coordination among multiple clinicians, overcoming barriers to access, and serving as a final safety checkpoint. Significant effort was required of patients and family caregivers to insure safe and effective pain medication management. Conclusion Health systems issues related to access to needed analgesics, medication safety in outpatient settings, and the effort expended by oncology patients and their family caregivers require more attention in future research and health-care reform initiatives.

Background The diagnosis of breast cancer, in combination with the anticipation of surgery, evokes fear, uncertainty, and anxiety in most women. Objective Study purposes were to examine in patients who underwent breast cancer surgery how ratings of state anxiety changed from the time of the preoperative assessment to 6 months after surgery and to investigate whether specific demographic, clinical, symptom, and psychosocial adjustment characteristics predicted the preoperative levels of state anxiety and/or characteristics of the trajectories of state anxiety. Interventions/methods Patients (n = 396) were enrolled preoperatively and completed the Spielberger State Anxiety inventory monthly for 6 months. Using hierarchical linear modeling, demographic, clinical, symptom, and psychosocial adjustment characteristics were evaluated as predictors of initial levels and trajectories of state anxiety. Results Patients experienced moderate levels of anxiety before surgery. Higher levels of depressive symptoms and uncertainty about the future, as well as lower levels of life satisfaction, less sense of control, and greater difficulty coping, predicted higher preoperative levels of state anxiety. Higher preoperative state anxiety, poorer physical health, decreased sense of control, and more feelings of isolation predicted higher state anxiety scores over time. Conclusions Moderate levels of anxiety persist in women for 6 months after breast cancer surgery. Implications for practice Clinicians need to implement systematic assessments of anxiety to identify high-risk women who warrant more targeted interventions. In addition, ongoing follow-up is needed to prevent adverse postoperative outcomes and to support women to return to their preoperative levels of function.

ContextDespite the increasing complexity of medication regimens for persistent cancer pain, little is known about how oncology outpatients and their family caregivers manage pain medications at home.ObjectivesTo describe the day-to-day management of pain medications from the perspectives of oncology outpatients and their family caregivers who participated in a randomized clinical trial of a psychoeducational intervention called the Pro-Self(©) Plus Pain Control Program. In this article, we focus on pain medication management in the context of highly individualized home environments and lifestyles.MethodsThis qualitative study was conducted as part of a randomized clinical trial, in which an embedded mixed methods research design was used. Audio-recorded dialogue among patients, family caregivers, and intervention nurses was analyzed using qualitative research methods.ResultsHome and lifestyle contexts for managing pain medications included highly individualized home environments, work and recreational activities, personal routines, and family characteristics. Pain medication management processes particularly relevant in these contexts included understanding, organizing, storing, scheduling, remembering, and taking the medications. With the exception of their interactions with the intervention nurses, most study participants had little involvement with clinicians as they worked through these processes.ConclusionPain medication management is an ongoing multidimensional process, each step of which has to be mastered by patients and their family caregivers when cancer treatment and supportive care are provided on an outpatient basis. Realistic patient- and family-centered skill-building interventions are needed to achieve effective and safe pain medication management in the contexts of individual home environments and lifestyles.

© Mary Ann Liebert, Inc. 2014.Background: Understanding normal volume asymmetry is essential for accurate assessment of limb volume changes following breast cancer (BC) treatment in which lymphatic function is disrupted. The purposes of this study were to evaluate for differences in dominant and nondominant limb volumes and to evaluate for interactions between the effects of dominance and side of cancer on limb volume. Methods and Results: This study evaluated preoperative limb volumes of 397 women enrolled in a prospective, longitudinal study of neuropathic pain and lymphedema. Volume was calculated from circumference. Limb resistance was measured with bioimpedance. Women were dichotomized into two groups: those whose cancer was on their dominant side and those whose cancer was on their nondominant side. Analyses of variance were used to evaluate for differences. In 47%, BC occurred on the side of the dominant limb. Except for the 30 to 40 centimeter (cm) limb volume segment, a main effect of dominance was found for all measures. The volume of the dominant limb was significantly greater than that of the nondominant limb. No main effects were found for side of cancer. A statistically significant interaction was found only at the 0 to 10cm limb volume segment. Conclusions: Prior to BC treatment, the dominant limb demonstrated lower bioimpedance resistance (-2.09%) and greater total limb volume (1.12%) than the nondominant limb. Segmental volume differences were greatest at the proximal forearm segment (2.31%) and least at the proximal arm segment (0.21%). This study provides evidence that preoperative volume assessment is important due to normal variability associated with limb dominance.

Purpose of the researchLittle is known about the relationships between pain, anxiety, and depression in women prior to breast cancer surgery. The purpose of this study was to evaluate for differences in anxiety, depression, and quality of life (QOL) in women who did and did not report the occurrence of breast pain prior to breast cancer surgery. We hypothesized that women with pain would report higher levels of anxiety and depression as well as poorer QOL than women without pain.Methods and sampleA total of 390 women completed self-report measures of pain, anxiety depression, and QOL prior to surgery.Key resultsWomen with preoperative breast pain (28%) were significantly younger, had a lower functional status score, were more likely to be Non-white and to have gone through menopause. Over 37% of the sample reported clinically meaningful levels of depressive symptoms. Almost 70% of the sample reported clinically meaningful levels of anxiety. Patients with preoperative breast pain reported significantly higher depression scores and significantly lower physical well-being scores. No between group differences were found for patients' ratings of state and trait anxiety or total QOL scores.ConclusionsOur a priori hypotheses were only partially supported. Findings from this study suggest that, regardless of pain status, anxiety and depression are common problems in women prior to breast cancer surgery.

Purpose Anxiety is common in patients undergoing radiation therapy (RT) and in their family caregivers (FCs). Little is known about individual differences in anxiety trajectories during and after RT. This study aimed to identify distinct latent classes of oncology patients and their FCs based on self-reported anxiety symptoms from the beginning to four months after the completion of RT. Method Using growth mixture modeling (GMM), longitudinal changes in Spielberger State Anxiety Inventory (STAI-S) scores among 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 FCs were evaluated to determine distinct anxiety symptom profiles. STAI-S scores were assessed just prior to, throughout the course of, and for four months following RT (total of 7 assessments). Baseline trait anxiety and depressive symptoms (during and after RT) were also assessed. Results The GMM analysis identified three latent classes of oncology patients and FCs with distinct trajectories of state anxiety: Low Stable ( n = 93, 36.9%), Intermediate Decelerating ( n = 82, 32.5%), and High ( n = 77, 30.6%) classes. Younger participants, women, ethnic minorities, and those with children at home were more likely to be classified in the High anxiety class. Higher levels of trait anxiety and depressive symptoms, at the initiation of RT, were associated with being in the High anxiety class. Conclusions Subgroups of patients and FCs with high, intermediate, and low mean levels of anxiety during and after RT were identified with GMM. Additional research is needed to better understand the heterogeneity of symptom experiences as well as comorbid symptoms in patients and FCs.

The purposes of this study were to identify distinct subgroups of patients based on self-reported sleep disturbance prior to through 6 months after breast cancer surgery and evaluate for differences in demographic, clinical, and symptom characteristics among these latent classes. Women (n = 398) who underwent unilateral breast cancer surgery were enrolled prior to surgery. Patients completed measures of functional status, sleep disturbance (i.e., General Sleep Disturbance Scale (GSDS); higher scores indicate higher levels of sleep disturbance), fatigue, attentional fatigue, depressive symptoms, and anxiety prior to surgery and monthly for 6 months. Three distinct classes of sleep disturbance trajectories were identified using growth mixture modeling. The high sustained class (55.0%) had high and the low sustained class (39.7%) had low GSDS scores prior to surgery that persisted for 6 months. The decreasing class (5.3%) had high GSDS score prior to surgery that decreased over time. Women in the high sustained class were significantly younger, had more comorbidity and poorer function, and were more likely to report hot flashes compared to the low sustained class. More women who underwent mastectomy or breast reconstruction were in the decreasing class. Decreasing and high sustained classes reported higher levels of physical fatigue, attentional fatigue, depressive symptoms, and anxiety compared to the low sustained class. A high percentage of women has significant sleep disturbance prior to surgery that persists during subsequent treatments (i.e., radiation therapy and chemotherapy). Clinicians need to perform routine assessments and initiate appropriate interventions to improve sleep prior to and following surgery.

Little is known about the occurrence and severity of sleep disturbance and fatigue between patients with common cancer diagnoses.Study purposes were to evaluate for differences in the occurrence rates of sleep disturbances and fatigue; evaluate for differences in the severity of sleep disturbance using both subjective and objective measures; and evaluate for differences in the severity of self-reported fatigue in patients with breast and prostate cancer at the initiation of radiation therapy (RT).Patients with breast (n=78) and prostate (n=82) cancer were evaluated before the initiation of RT using the Pittsburgh Sleep Quality Index, General Sleep Disturbance Scale, Lee Fatigue Scale, and wrist actigraphy. Differences in sleep disturbance and fatigue between groups were evaluated using independent sample t-tests and Chi-square analyses.Occurrence rates for sleep disturbance (P0.0001) and fatigue (P=0.03) were significantly higher in patients with breast compared with prostate cancer. Patients with breast cancer self-reported significantly higher levels of sleep disturbance (P=0.008) and fatigue (P=0.005) than patients with prostate cancer. However, using actigraphy, patients with prostate cancer had poorer sleep efficiency (P=0.02) than patients with breast cancer.Based on self-report, patients with breast cancer experience sleep disturbance more frequently and with greater severity than patients with prostate cancer. Objective measures of sleep disturbance suggest that prostate cancer patients have more severe sleep disturbance than breast cancer patients. All the patients experienced poor sleep quality and fatigue, which suggests that oncology patients need to be assessed for these symptoms.

Background Little is known about the relationships between sleep parameters and fatigue in patients at the initiation of radiation therapy (RT). Objectives The objectives of this study were to describe values for nocturnal sleep/rest, daytime wake/activity, and circadian activity rhythm parameters measured using actigraphy and to evaluate the relationships between these objective parameters and subjective ratings of sleep disturbance and fatigue severity, in a sample of patients at the initiation of RT. Methods Patients (n = 185) with breast, prostate, lung, or brain cancer completed self-report measures for sleep disturbance (ie, Pittsburgh Sleep Quality Index, General Sleep Disturbance Scale) and fatigue (Lee Fatigue Scale) and wore wrist actigraphs for a total of 48 hours prior to beginning RT. Actigraphy data were analyzed using the Cole-Kripke algorithm. Spearman rank correlations were calculated between variables. Results Approximately 30% to 50% of patients experienced sleep disturbance, depending on whether clinically significant cutoffs for the subjective or objective measures were used to calculate occurrence rates. In addition, these patients reported moderate levels of fatigue. Only a limited number of significant correlations were found between the subjective and objective measures of sleep disturbance. Significant positive correlations were found between the subjective, but not the objective measures of sleep disturbance and fatigue. Conclusions A significant percentage of oncology patients experience significant disturbances in sleep-wake circadian activity rhythms at the initiation of RT. The disturbances occur in both sleep initiation and sleep maintenance. Implications for practice Patients need to be assessed at the initiation of RT for sleep disturbance, so appropriate treatment is initiated.

A large proportion of oncology outpatients with bone metastasis report unrelieved pain that significantly interferes with daily functioning and quality of life. However, little is known about the longitudinal pattern of pain intensity and analgesic prescriptions or use. Moreover, despite considerable advantages, the use of sophisticated statistical techniques, such as hierarchical linear modeling (HLM) has not been applied to the study of pain and analgesic outcomes. In a prospective longitudinal study, HLM was used to explore predictors of pain intensity and analgesic prescription and intake at the time of enrollment into the study (intercept) and over the course of 6 weeks (trajectory) in a sample of oncology outpatients with bone metastasis who received standard care for pain. In addition to corroborating known predictors of pain intensity, previously unrecognized variables were found that appear to affect both pain and analgesic outcomes. Importantly, some of the predictors of the trajectories of pain intensity and analgesic use (ie, pain-related distress and Pain Management Index (PMI) scores) are particularly amenable to interventions. Findings from this study suggest that sophisticated statistical modeling can be used in pain research to identify individual risk factors and propose novel targets that can be used to improve pain management in oncology outpatients with bone metastasis. Perspective Findings from this study suggest that a large amount of inter-individual variability exists in patients' experiences with cancer pain and analgesic use. Future studies need to elucidate the mechanisms that underlie these differences.

Purpose This study compared the occurrence rates for and severity ratings of sleep disturbance in patient-family caregiver (FC) dyads. Patients and Methods In total, 102 dyads were recruited from two radiation therapy (RT) departments. Patients and their FCs completed the Pittsburgh Sleep Quality Index (PSQI) and the General Sleep Disturbance Scale (GSDS) and wore wrist actigraphs to obtain subjective and objective measures of the occurrence and severity of sleep disturbance at the initiation of RT. Match paired t tests were used to evaluate for dyadic differences. Results No differences were found in the occurrence of clinically significant levels of sleep disturbance between patients and their FCs that ranged between 40% and 50% using subjective and objective measures. Few differences were found in the severity of any of the sleep-wake parameters between patients and FCs using both the subjective and objective measures of sleep disturbance. Conclusion The findings from this study suggest that patients with cancer and their FCs experience similar levels of sleep disturbance and that both groups could benefit from interventions that aim to promote restful sleep. In addition to routine and systematic assessment of sleep disturbance by oncology clinicians, interventions are needed that take into account the specific needs of the patient and the FC as well as the potential for partners' sleep patterns to influence one another.

Attentional fatigue is a decreased capacity to direct attention (Cimprich, 1992a). This capacity is defined by three concepts: selectivity, which is the ability to highlight one stimulus while ignoring others; sustained focus, which is the maintenance of selectivity over time; and limited capacity, which is a ceiling on the number of stimuli that can be processed successfully at any one time (Cimprich, 1992a; Kaplan & Kaplan, 1982; Posner & Boies, 1971). Attentional fatigue is not physical fatigue, so a person can experience the former with or without the latter (Cimprich, 1992b). In addition, the cognitive changes associated with chemotherapy that are popularly referred to as “chemo brain” include, but are not limited to, attentional fatigue (Hess & Insel, 2007). Anatomically, attention is thought to reside in the anterior and posterior attention systems of the frontal and parietal cortices (Cimprich, 1995; Posner & Dehaene, 1994; Posner & Petersen, 1990). This hypothesis is supported by findings from a recent imaging study that evaluated for changes in the prefrontal and anterior cingulate cortices of women with breast cancer prior to chemotherapy (Cimprich et al., 2009) and found significantly larger differences in the activation of the right inferior frontal gyrus compared to healthy controls. In addition, in these women with breast cancer, more areas of the brain were activated during the completion of tasks that required them to direct their attention. There are two types of attention, involuntary and voluntary (James, 1983; Kaplan & Kaplan, 1982). Some stimuli that originate in our thoughts or in the world around us (i.e., our internal and external environments) engage involuntary attention without effort (Cimprich, 1992a; James, 1983; Kaplan & Kaplan, 1982). These stimuli include nature, things that affect survival, and things that fascinate us (Cimprich, 1992a; James, 1983; Kaplan & Kaplan, 1982). Other stimuli must consciously be selected for processing by voluntary attention, which requires effort that reduces our capacity to direct attention further (Cimprich, 1992a; James, 1983; Kaplan & Kaplan, 1982). Voluntary attention is required to act purposefully (Lezak, 1982), to monitor one’s self, and to inhibit emotional reactions (Cimprich, 1992a). As involuntary attention is drawn to a greater diversity and intensity of sensory information, experienced as distraction, one must expend greater effort to direct voluntary attention (Cimprich, 1992a; Kaplan & Kaplan, 1982). After diagnosis with breast cancer, involuntary attention is drawn to the threatening information received and to the unfamiliar physical environment in which treatment occurs, both of which pertain to survival (Cimprich, 1992b). The concept of limited capacity suggests that the direction of voluntary attention during the time of diagnosis and treatment would require increased effort, which results in attentional fatigue and its sequelae (e.g., irritability when presented with further demands on one’s attention and a decreased ability to focus on selected stimuli) (Cimprich, 1992b; Kaplan & Kaplan, 1982). Three cross-sectional studies evaluated the correlates of self-reported attentional fatigue, as measured using the Attentional Function Index (AFI), before treatment in women diagnosed with breast cancer (Cimprich, 1999; Cimprich, So, Ronis, & Trask, 2005; Lehto & Cimprich, 1999). Across these studies with a total of 303 women, significant correlates of higher levels of attentional fatigue included younger age, pre-menopausal status, higher symptom distress scores and greater number of symptoms, greater mood disturbance, and high versus low-to-moderate anxiety. Two papers from the same study described self-reported attentional fatigue in women following breast cancer surgery. In these papers, higher levels of attentional fatigue were reported by women with greater mood disturbance (Cimprich, 1992b) and in those assessed closer to the time of surgery (Cimprich, 1993). In a more recent cross-sectional study of breast cancer survivors (Von Ah, Russell, Storniolo, & Carpenter, 2009), higher levels of attentional fatigue correlated with younger age, higher levels of depression and physical fatigue, and lower levels of psychological well-being and physical functioning. In a longitudinal study that evaluated self-reported attentional fatigue in women undergoing chemotherapy for breast cancer (Jansen, Dodd, Miaskowski, Dowling, & Kramer, 2008), higher levels of attentional fatigue were significantly correlated with the administration of chemotherapy and higher levels of depression. A number of studies have employed measures other than the AFI to assess self-reported attentional fatigue alone or in combination with other cognitive changes in patients with cancer. In a cross-sectional study of breast cancer survivors (Mehnert et al., 2007), higher levels of attentional fatigue, measured using a German questionnaire for self-perceived deficits in attention (Zimmermann, Merser, Poser, & Sedelmeier, 1991), were associated with higher levels of physical fatigue and lower health-related quality of life. Across two studies (Schagen et al., 1999; van Dam et al., 1998) that used a Dutch questionnaire that assessed for cognitive problems in daily life (Huyser, 1993), higher levels of attentional fatigue were associated with higher levels of anxiety and depression and a lower quality of life. Across three studies (Castellon et al., 2004; Jenkins et al., 2006; Jenkins, Shilling, Fallowfield, Howell, & Hutton, 2004) that used the Cognitive Failures Questionnaire (Broadbent, Cooper, FitzGerald, & Parkes, 1982), higher levels of attentional fatigue were associated with higher levels of depression, trait anxiety, psychological distress, and physical fatigue, as well as a lower quality of life. Finally, in an imaging study (Ferguson, McDonald, Saykin, & Ahles, 2007) that used the Multiple Ability Self-Report Questionnaire (Seidenberg, Haltiner, Taylor, Hermann, & Wyler, 1994), a higher level of attentional fatigue was associated with the administration of chemotherapy. Taken together, the findings from these studies suggest that attentional fatigue is associated with decreased physical functioning, higher levels of mood disturbance, and poorer quality of life. However, it is not known how well the AFI, which was used in the present study, correlates with these other subjective measures of attentional fatigue. No studies were found that examined the trajectories of self-reported attentional fatigue in women with breast cancer before, during, and after radiation therapy (RT). An increased understanding of the predictors and trajectories of attentional fatigue in women with breast cancer may help clinicians identify patients at risk for more severe attentional fatigue and may guide the development of interventions tailored to their individual experiences. Therefore, the purposes of this study, in a sample of women who underwent RT for breast cancer, were (1) to examine how self-ratings of attentional fatigue changed from the time of simulation to four months after the completion of RT and (2) to investigate whether specific participant, disease, and symptom characteristics predicted initial levels of attentional fatigue and/or characteristics of the trajectories of attentional fatigue.

Background Fatigue is a significant problem associated with radiation therapy (RT). Objective This study examined how evening and morning fatigue changed from the time of simulation to 4 months after the completion of RT and investigated whether specific demographic and disease characteristics and baseline severity of symptoms predicted the initial levels of fatigue and characteristics of the trajectories of fatigue. Methods Seventy-three women with breast cancer completed questionnaires that assessed sleep disturbance, depression, anxiety, and pain prior to the initiation of RT and the Lee Fatigue Scale, over 6 months. Descriptive statistics and hierarchical linear modeling were used for data analysis. Results Large amounts of interindividual variability were found in the trajectories of fatigue. Evening fatigue at baseline was negatively influenced by having children at home and depression. The trajectory of evening fatigue was worse for women who were employed. Morning fatigue at baseline was influenced by younger age, lower body mass index, and the degree of sleep disturbance and trait anxiety. Trajectories of morning fatigue were worse for patients with a higher disease stage and more medical comorbidities. Conclusion Interindividual and diurnal variability in fatigue found in women with breast cancer is similar to that found in men with prostate cancer. However, the predictors of interindividual variability in fatigue between these 2 cohorts were different. Implications for practice Diurnal variability and different predictors for morning and evening fatigue suggest different underlying mechanisms. The various predictors of fatigue need to be considered in the design of future intervention studies.

Context Little is known about the phenotypic and molecular characteristics associated with various domains of quality of life (QOL) in women following breast cancer surgery. Objectives In a sample of women with breast cancer (n= 398), purposes were: to identify latent classes with distinct trajectories of QOL from prior to through six months following surgery and to evaluate for differences in demographic and clinical characteristics, as well as for polymorphisms in cytokine genes, between these latent classes. Methods Latent class analyses were done to identify subgroups of patients with distinct QOL outcomes. Candidate gene analyses were done to identify cytokine gene polymorphisms associated with various domains of QOL (i.e., physical, psychological, spiritual, social). Results One latent class was identified for the psychological and spiritual domains. Two latent classes were identified for the social domain and overall QOL scores. Three latent classes were identified for the physical domain. For the physical and social domains, as well as for the overall QOL scores, distinct phenotypic characteristics (i.e., younger age, poorer functional status, higher body mass index, and receipt of adjuvant chemotherapy) and a number of cytokine gene polymorphisms (CXCL8, NFKB2, TNFSF, IL1B, IL13, and NFKB1) were associated with membership in the lower QOL classes. Conclusions Findings suggest that women experience distinctly different physical well-being, social well-being, and total QOL outcomes during and following breast cancer surgery. The genetic associations identified suggest that cytokine dysregulation influences QOL outcomes. However, specific QOL domains may be impacted by different cytokines. Key words quality of life; cytokine genes; breast cancer; polymorphism; growth mixture modelling

The purposes of this study were to identify the number and types of symptom clusters using yes/no responses from the Memorial Symptom Assessment Scale, identify the number and types of symptom clusters using severity scores from the Memorial Symptom Assessment Scale, compare the identified symptom clusters derived using severity scores to those derived using occurrence ratings, and evaluate for differences in symptom cluster severity scores between patients with breast and prostate cancer at the end of radiation therapy. Separate exploratory factor analyses were performed to determine the number of symptom clusters based on symptom occurrence rates and symptom severity ratings. Although specific symptoms within each symptom cluster were not identical, 3 very similar symptom clusters (ie, "mood-cognitive" symptom cluster, "sickness-behavior" symptom cluster, "treatment-related" symptom cluster) were identified regardless of whether occurrence rates or severity ratings were used to create the symptom clusters at the end of radiation therapy. However, the factor solution derived using the severity ratings fit the data better. Significant differences in severity scores for all 3 symptom clusters were found between patients with breast and prostate cancer. For all 3 symptom clusters, the patients with breast cancer had higher symptom cluster severity scores than the patients with prostate cancer.

Although fatigue and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, tumor necrosis factor-alpha (TNFA-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and fatigue. Multiple linear regression was used to assess the effect of the TNFA genotype and other covariates on mean sleep disturbance and fatigue scores. Hierarchical linear modeling was used to determine the effect of TNFA genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p = .09) and morning fatigue (p = .02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the TNFA gene and the severity of sleep disturbance and morning fatigue in oncology patients and their family caregivers.

Predictors of and trajectories for evening and morning fatigue were evaluated in family caregivers of oncology patients using hierarchical linear modeling. Evening fatigue trajectory fit a quadratic model. Predictors included baseline sleep disturbances in family caregivers and baseline evening fatigue in patients. Morning fatigue trajectory fit a linear model. Predictors were baseline trait anxiety, levels of perceived family support, and baseline morning fatigue in patients. Findings suggest considerable inter-individual variability in the trajectories of evening and morning fatigue. Evaluating family caregivers for sleep disturbance, anxiety, and poor family support, as well as high levels of patient fatigue, could identify those family caregivers at highest risk for sustained fatigue trajectories.

Fatigue is the most common and distressing symptom reported by patients undergoing radiation therapy (RT). However, limited information is available on the trajectories of fatigue, as well as on the predictors of interindividual variability in fatigue. This study evaluated a sample of patients who underwent RT for prostate cancer to examine how ratings of evening and morning fatigue changed from the time of simulation to four months after the completion of RT and to investigate whether specific patient, disease, and symptom characteristics predicted the initial levels of fatigue and/or characteristics of the trajectories of evening and morning fatigue. Using hierarchical linear modeling, a large amount of interindividual variability was demonstrated in the trajectories of evening and morning fatigue. Findings from this study suggest that younger men with a higher level of fatigue at the time of the simulation visit were at increased risk for higher levels of evening and morning fatigue over the course of RT. In addition, the level of morning fatigue over the course of RT appears to depend on the patient's level of depression at the time of the simulation visit. In future studies, the use of hierarchical linear modeling as an analytic tool will assist in the identification of patients who are most at risk for prolonged fatigue trajectories. This type of analysis may lead to the identification of subgroups of patients who are at higher risk for negative outcomes and who require different types of interventions for the fatigue associated with RT.

Purpose In a sample of family caregivers (FCs) of patients with prostate cancer who were to begin radiation therapy (RT), the purposes were to determine the prevalence and severity of depression, anxiety, pain, sleep disturbance, and fatigue; determine the relationships among these symptoms and between these symptoms and functional status and quality of life (QOL); evaluate for differences in functional status and QOL between FCs with low and high levels of these symptoms; and determine which factors predicted FCs’ functional status and QOL. Patients and Methods FCs were recruited before patients initiated RT and completed self-report questionnaires that evaluated demographic characteristics, symptoms, functional status, and QOL. Results Sixty female FCs participated in the study. On the basis of established cut point scores for each symptom questionnaire, 12.2% of the FCs had clinically meaningful levels of depression, 40.7% anxiety, 15.0% pain, 36.7% sleep disturbance, 33.3% morning fatigue, and 30.0% evening fatigue. FCs who were older and who had lower levels of state anxiety and higher levels of depression, morning fatigue, and pain reported significantly poorer functional status (R2 = 38.7%). FCs who were younger, had more years of education, were working, and who had higher levels of depression, morning fatigue, sleep disturbance, and lower levels of evening fatigue reported significantly lower QOL scores (R2 = 70.1%). Conclusion A high percentage of FCs experienced clinically meaningful levels of a variety of symptoms. These symptoms have a negative impact on the FCs’ functional status and QOL.

Previously, we demonstrated, in a randomized clinical trial, the effectiveness of a psychoeducational intervention to decrease pain intensity scores and increase patients' knowledge of cancer pain management with a sample of oncology patients with pain from bone metastasis. In the present study, we evaluated for changes in mood states (measured using the Profile of Mood States), quality of life (QOL; measured using the Medical Outcomes Study Short Form-36 (SF-36)), and pain's level of interference with function (measured using the Brief Pain Inventory (BPI)) from baseline to the end of the intervention first between the intervention and the standard care groups and then within the intervention group based on the patients' level of response to the intervention (i.e., patients were classified as non-responders, partial responders, or responders). No differences were found in any of these outcome measures between patients in the standard care and intervention groups. However, when patients in the intervention group were categorized using a responder analysis approach, significant differences in the various outcome measures were found among the three respondent groups. Differences in the physical and mental component summary scores on the SF-36 and the interference items on the BPI, among the three respondent groups, were not only statistically significant but also clinically significant. The use of responder analysis in analgesic trials may help to identify unique subgroups of patients and lead to the development of more effective psychoeducational interventions.

PURPOSE/OBJECTIVES To evaluate gender differences in quality of life (QOL), demographic, clinical, and symptom characteristics. DESIGN Prospective, observational. SETTING Two radiation oncology departments in northern California. SAMPLE 185 patients before initiation of radiation therapy (RT). METHODS At their RT simulation visit, patients completed a demographic questionnaire, a measure of QOL, and symptom-specific scales. Backward elimination regression analyses were conducted to determine the significant predictors of QOL . MAIN RESEARCH VARIABLES QOL, gender, and 20 potential predictors . FINDINGS In women, depressive symptoms, functional status, age, and having children at home explained 64% of the variance in QOL. In men, depressive symptoms, state anxiety, number of comorbidities, being a member of a racial or ethnic minority, and age explained 70% of the variance in QOL . CONCLUSIONS Predictors of QOL differed by gender. Depressive symptom score was the greatest contributor to QOL in both genders. . IMPLICATIONS FOR NURSING Nurses need to assess for QOL and depression at the initiation of RT. Knowledge of the different predictors of QOL may be useful in the design of gender-specific interventions to improve QOL.

© 2014 Elsevier Ltd. Purpose of the research: Evaluate for associations between variations in genes involved in catecholaminergic, gamma-aminobutyric acid (GABA)-ergic, and serotonergic mechanisms of neurotransmission and attentional function latent classes. Patients and methods: This descriptive, longitudinal study was conducted at two radiation therapy departments. The sample included three latent classes of individuals with distinct trajectories of self-reported attentional function during radiation therapy, who were previously identified using growth mixture modeling among 167 oncology patients and 85 of their family caregivers. Multivariable models were used to evaluate for genotypic associations of neurotransmission genes with attentional function latent class membership, after controlling for covariates. Results: Variations in catecholaminergic (i.e., ADRA1D rs4815675, SLC6A3 rs37022), GABAergic (i.e., SLC6A1 rs2697138), and serotonergic (i.e., HTR2A rs2296972, rs9534496) neurotransmission genes were significant predictors of latent class membership in multivariable models. Conclusions: Findings suggest that variations in genes that encode for three distinct but related neurotransmission systems are involved in alterations in attentional function. Knowledge of both phenotypic and genetic markers associated with alterations in attentional function can be used by clinicians to identify patients and family caregivers who are at higher risk for this symptom. Increased understanding of the genetic markers associated with alterations in attentional function may provide insights into the underlying mechanisms for this significant clinical problem.

Persistent pain after breast cancer surgery is a common clinical problem. Given the role of potassium channels in modulating neuronal excitability, coupled with recently published genetic associations with preoperative breast pain, we hypothesized that variations in potassium channel genes will be associated with persistent postsurgical breast pain. In this study, associations between 10 potassium channel genes and persistent breast pain were evaluated. Using growth mixture modeling (GMM), 4 distinct latent classes of patients, who were assessed before and monthly for 6 months after breast cancer surgery, were identified previously (ie, No Pain, Mild Pain, Moderate Pain, Severe Pain). Genotyping was done using a custom array. Using logistic regression analyses, significant differences in a number of genotype or haplotype frequencies were found between: Mild Pain vs No Pain and Severe Pain vs No Pain classes. Seven single-nucleotide polymorphisms (SNPs) across 5 genes (ie, potassium voltage-gated channel, subfamily A, member 1 [KCNA1], potassium voltage-gated channel, subfamily D, member 2 [KCND2], potassium inwardly rectifying channel, subfamily J, members 3 and 6 (KCNJ3 and KCNJ6), potassium channel, subfamily K, member 9 [KCNK9]) were associated with membership in the Mild Pain class. In addition, 3 SNPs and 1 haplotype across 4 genes (ie, KCND2, KCNJ3, KCNJ6, KCNK9) were associated with membership in the Severe Pain class. These findings suggest that variations in potassium channel genes are associated with both mild and severe persistent breast pain after breast cancer surgery. Although findings from this study warrant replication, they provide intriguing preliminary information on potential therapeutic targets.

© 2014, Springer-Verlag Berlin Heidelberg. Purpose: Anxiety is common among cancer patients and their family caregivers (FCs) and is associated with poorer outcomes. Recently, associations between inflammation and anxiety were identified. However, the relationship between variations in cytokine genes and anxiety warrants investigation. Therefore, phenotypic and genotypic characteristics associated with trait and state anxiety were evaluated in a sample of 167 oncology patients with breast, prostate, lung, or brain cancer and 85 of their FCs. Methods: Using multiple regression analyses, the associations between participants’ demographic and clinical characteristics as well as variations in cytokine genes and trait and state anxiety were evaluated. Results: In the bivariate analyses, a number of phenotypic characteristics were associated with both trait and state anxiety (e.g., age, functional status). However, some associations were specific only to trait anxiety (e.g., number of comorbid conditions) or state anxiety (e.g., participation with a FC). Variations in three cytokine genes (i.e., interleukin (IL) 1 beta, IL1 receptor 2 (IL1R2), nuclear factor kappa beta 2 (NFKB2)) were associated with trait anxiety, and variations in two genes (i.e., IL1R2, tumor necrosis factor alpha (TNFA)) were associated with state anxiety. Conclusions: These findings suggest that both trait and state anxiety need to be assessed in oncology patients and their FCs. Furthermore, variations in cytokine genes may contribute to higher levels of anxiety in oncology patients and their FCs.

PURPOSE/OBJECTIVES: To identify subgroups of outpatients with cancer based on their experiences with the symptoms of fatigue, sleep disturbance, depression, and pain; to explore whether patients in the subgroups differed on selected demographic, disease, and treatment characteristics; and to determine whether patients in the subgroups differed on two important patient outcomes: functional status and quality of life (QOL). DESIGN: Descriptive, correlational study. SETTING: Four outpatient oncology practices in northern California. SAMPLE: 191 outpatients with cancer receiving active treatment. METHODS: Patients completed a demographic questionnaire, Karnofsky Performance Status scale, Lee Fatigue Scale, General Sleep Disturbance Scale, Center for Epidemiological Studies Depression Scale, Multidimensional Quality-of-Life Scale Cancer, and a numeric rating scale of worst pain intensity. Medical records were reviewed for disease and treatment information. Cluster analysis was used to identify patient subgroups based on patients symptom experiences. Differences in demographic, disease, and treatment characteristics as well as in outcomes were evaluated using analysis of variance and chi square analysis. MAIN RESEARCH VARIABLES: Subgroup membership, fatigue, sleep disturbance, depression, pain, functional status, and QOL. FINDINGS: Four relatively distinct patient subgroups were identified based on patients experiences with four highly prevalent and related symptoms. CONCLUSIONS: The subgroup of patients who reported low levels of all four symptoms reported the best functional status and QOL. IMPLICATIONS FOR NURSING: The findings from this study need to be replicated before definitive clinical practice recommendations can be made. Until that time, clinicians need to assess patients for the occurrence of multiple symptoms that may place them at increased risk for poorer outcomes.

UnlabelledInterindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N=398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction.PerspectiveSubgroups of women with persistent postsurgical breast pain differed primarily with respect to the severity rather than the nature or underlying mechanisms of breast pain. Pervasive sensory loss and the association between persistent breast pain and sustained interference with function suggest the need for long-term clinical follow-up.

Qualitative research may be combined fruitfully with intervention studies, but few examples provide detailed methodological strategies for doing so. In this article, we describe the qualitative component of a randomized clinical trial (RCT) of the PRO-SELF© Pain Control Program, an intervention that provides individualized education, coaching, and support for cancer pain management. We conducted three qualitative analyses of verbatim transcripts of “real-time” audiotaped intervention sessions. As a result, we were better able to ascertain the nature of the individualized coaching component of the intervention, patient and family caregiver use of selected intervention tools, and reasons the intervention did not work for some patients. Study results were used to increase the specificity with which the coaching portion of the intervention is described in the intervention protocol. © 2005 Wiley Periodicals, Inc. Res Nurs Health 28: 268–280, 2005

While chronic pain is experienced by approximately 50-90% of patients with metastatic cancer, little is known about sex differences in chronic cancer pain. Therefore, the purposes of this study, in a sample of oncology outpatients (n=187) who were experiencing pain from bone metastasis, were: 1) to determine if there were sex differences in various pain characteristics, including pain intensity, and 2) to determine if there were sex differences in the prescription and consumption of analgesic medications. No significant sex differences were found in any of the baseline pain characteristics. In addition, no significant sex differences were found in analgesic prescriptions or intake of analgesic medications. Of note, men reported significantly higher pain interference scores for sexual activity than women. The study findings are important because they suggest that, unlike in acute pain, sex may not influence patients' perceptions of and responses to chronic cancer pain.

Purpose This randomized clinical trial tested the effectiveness of the PRO-SELF Pain Control Program compared with standard care in decreasing pain intensity scores, increasing appropriate analgesic prescriptions, and increasing analgesic intake in oncology outpatients with pain from bone metastasis. Patients and Methods Patients were randomly assigned to the PRO-SELF intervention (n = 93) or standard care (n = 81). Patients in the standard care arm were seen by a research nurse three times and were called three times by phone between the home visits. PRO-SELF group patients were seen by specially trained intervention nurses and received a psychoeducational intervention, were taught how to use a pillbox, and were given written instructions on how to communicate with their physician about unrelieved pain and the need for changes in their analgesic prescriptions. Patients were coached during two follow-up home visits and three phone calls on how to improve their cancer pain management. Results Pain intensity scores decreased significantly from baseline (all P < .0001) in the PRO-SELF group (ie, least pain, 28.4%; average pain, 32.5%; and worst pain, 27.0%) compared with the standard care group (ie, least increased by 14.6%, average increased by 1.9%, and worst decreased by 1.2%). The percentage of patients in the PRO-SELF group with the most appropriate type of analgesic prescription increased significantly from 28.3% to 37.0% (P = .008) compared with a change from 29.6% to 32.5% in the standard care group. Conclusion The use of a psychoeducational intervention that incorporates nurse coaching within the framework of self-care can improve the management of cancer pain.

PURPOSE/OBJECTIVES: To describe the PRO-SELF(c): Pain Control Program, an educational approach that provides patients and family caregivers with the knowledge, skills, and nursing support needed to improve pain relief. DATA SOURCES: Published research studies, articles, and conference abstracts. DATA SYNTHESIS: Patients with cancer and family caregivers lack knowledge about pain management and side effects. Engaging in self-care behaviors improves patients' health outcomes. CONCLUSIONS: The PRO-SELF: Pain Control Program is an effective approach that can be used to help patients with cancer and their family caregivers obtain the knowledge and skills that are needed to manage pain. Three key strategies for delivering the PRO-SELF program are (a) provision of information using academic detailing, (b) skill building with ongoing nurse coaching, and (c) interactive nursing support. IMPLICATIONS FOR NURSING: Adequate pain relief is vital to decreasing cancer morbidity and improving patients' quality of life. The PRO-SELF: Pain Control Program should be implemented in all settings where cancer care takes place.

The purpose of this study was to describe the difficulties with pain management that patients and family caregivers bring to a nurse's attention during a teaching and coaching intervention. Data were obtained from audiotaped and transcribed interactions between intervention nurses and patients (n = 52) and their family caregivers (n = 33) who were participating in a randomized clinical trial of a nursing intervention called the PRO-SELF Copyright Pain Control Program. Using qualitative content analysis, we found that patients had difficulty in seven areas when they attempted to put a pain management regimen into practice, namely: obtaining the prescribed medication(s), accessing information, tailoring prescribed regimens to meet individual needs, managing side effects, cognitively processing information, managing new or unusual pain, and managing multiple symptoms simultaneously. The findings from this study suggest that the provision of information about cancer pain management to patients and their family caregivers is not sufficient to improve pain control in the home care setting. Patients and their family caregivers require ongoing assistance with problem-solving to optimize their pain management regimen.

Purpose/objectives To describe the usefulness of daily pain management diaries to outpatients with cancer who participated in a randomized clinical trial of the PRO-SELF Pain Control Program. Design Randomized clinical trial in which a daily pain management diary was used for data collection in the control group and for data collection and nurse coaching regarding the pain management program in the intervention group. Setting Seven outpatient oncology settings. Sample 155 patients with pain from bone metastases and 90 family caregivers. Methods Content and statistical analysis of audiotaped answers to a semistructured questionnaire. Main research variables Patients' and family caregivers' perceptions of the usefulness of a daily pain management diary; specific ways in which the diary was used. Findings Patients in both the intervention (75%) and control groups (73%) found the diary useful. The diary was used to heighten awareness of pain, guide pain management behavior, enhance a sense of control, and facilitate communication. Family caregivers in both groups also reported that the diary was useful. Conclusions The completion of a daily pain management diary is useful to patients and family caregivers and may function as an intervention for self-care. Implications for nursing Research-based evidence supports the importance of using a daily pain management diary in clinical practice.

Pain, fatigue, sleep disturbance, and depression are common and frequently co-occurring symptoms in oncology patients. This symptom cluster is often attributed to the release of proinflammatory cytokines. The purposes of this study were to determine whether distinct latent classes of patients with breast cancer ( n = 398) could be identified based on their experience with this symptom cluster, whether patients in these latent classes differed on demographic and clinical characteristics and whether variations in cytokine genes were associated with latent class membership. Three distinct latent classes were identified: “all low” (61.0%), “low pain and high fatigue” (31.6%), “all high” (7.1%). Compared to patients in the all low class, patients in the all high class were significantly younger, had less education, were more likely to be non-White, had a lower annual income, were more likely to live alone, had a lower functional status, had a higher comorbidity score, and had more advanced disease. Significant associations were found between interleukin 6 (IL6) rs2069845, IL13 rs1295686, and tumor necrosis factor alpha rs18800610 and latent class membership. Findings suggest that variations in pro- and anti-inflammatory cytokine genes are associated with this symptom cluster in breast cancer patients.

PURPOSE/OBJECTIVES: To identify latent classes of individuals with distinct quality-of-life (QOL) trajectories, to evaluate for differences in demographic characteristics between the latent classes, and to evaluate for variations in pro- and anti-inflammatory cytokine genes between the latent classes. DESIGN: Descriptive, longitudinal study. SETTING: Two radiation therapy departments located in a comprehensive cancer center and a community-based oncology program in northern California. SAMPLE: 168 outpatients with prostate, breast, brain, or lung cancer and 85 of their family caregivers (FCs). METHODS: Growth mixture modeling (GMM) was employed to identify latent classes of individuals based on QOL scores measured prior to, during, and for four months following completion of radiation therapy. Single nucleotide polymorphisms (SNPs) and haplotypes in 16 candidate cytokine genes were tested between the latent classes. Logistic regression was used to evaluate the relationships among genotypic and phenotypic characteristics and QOL GMM group membership. MAIN RESEARCH VARIABLES: QOL latent class membership and variations in cytokine genes. FINDINGS: Two latent QOL classes were found: higher and lower. Patients and FCs who were younger, identified with an ethnic minority group, had poorer functional status, or had children living at home were more likely to belong to the lower QOL class. After controlling for significant covariates, between-group differences were found in SNPs in interleukin 1 receptor 2 (IL1R2) and nuclear factor kappa beta 2 (NFKB2). For IL1R2, carrying one or two doses of the rare C allele was associated with decreased odds of belonging to the lower QOL class. For NFKB2, carriers with two doses of the rare G allele were more likely to belong to the lower QOL class. CONCLUSIONS: Unique genetic markers in cytokine genes may partially explain interindividual variability in QOL. IMPLICATIONS FOR NURSING: Determination of high-risk characteristics and unique genetic markers would allow for earlier identification of patients with cancer and FCs at higher risk for poorer QOL. Knowledge of these risk factors could assist in the development of more targeted clinical or supportive care interventions for those identified.

Purpose In this prospective, longitudinal study, we extend our findings on persistent breast pain in patients ( n = 398) following breast cancer surgery and evaluate the prevalence and characteristics of persistent pain in the arm/shoulder. In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the arm pain classes, were evaluated. Methods and sample Patients were recruited from Breast Care Centers located in a Comprehensive Cancer Center, two public hospitals, and four community practices. Patients were assessed prior to and monthly for six months following breast cancer surgery. Results Using growth mixture modeling, patients were classified into no (41.6%), mild (23.6%), and moderate (34.8%) arm pain classes based on ratings of worst arm/shoulder pain. Compared to the no pain class, patients in the moderate pain class were significantly younger, had a higher body mass index, and were more likely to report preoperative breast pain and swelling in the affected breast. In addition, patients in the moderate pain class reported higher levels of depression, anxiety, and sleep disturbance than the no pain class. Conclusions Findings suggest that approximately 35% of women experience persistent levels of moderate arm/shoulder pain in the first six months following breast cancer surgery. Moderate arm/shoulder pain is associated with clinically meaningful decrements in functional status and quality of life.

Purpose: This study explored the relationships between variations in cytokines genes and depressive symptoms in a sample of patients who were assessed prior to and for six months following breast cancer surgery. Phenotypic differences between Resilient (n = 155) and Subsyndromal (n = 180) depressive symptom classes, as well as variations in cytokine genes were evaluated. Method: Patients were recruited prior to surgery and followed for six months. Growth mixture modeling was used to identify distinct latent classes based on Center for Epidemiological Studies Depression (CES-D) Scale scores. Eighty-two single nucleotide polymorphisms and 35 haplotypes among 15 candidate cytokine genes were evaluated. Results: Patients in the Subsyndromal class were significantly younger, more likely to be married or partnered, and reported a significantly lower functional status. Variation in three cytokine genes (i.e., interferon gamma receptor 1 (IFNGR1 rs9376268), interleukin 6 (IL6 rs2069840), tumor necrosis factor alpha (TNFA rs1799964)), as well as age and functional status predicted membership in the Subsyndromal versus the Resilient class. Conclusions: A variation in TNFA that was associated with Subsyndromal depressive symptoms in a sample of patients and their family caregivers was confirmed in this sample. Variations in cytokine genes may place these patients at higher risk for the development of Subsyndromal levels of depressive symptoms. © 2014 Elsevier Ltd. All rights reserved.

Subgroups of individuals may be at greater risk of cytokine-induced changes in attentional function. The purposes of this study were to identify subgroups of individuals with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) differences among these subgroups. Self-reported attentional function was evaluated in 252 participants (167 oncology patients and 85 family caregivers) using the Attentional Function Index before radiation therapy and at six additional assessments over 6 months. Three latent classes of attentional function were identified using growth mixture modeling: moderate (36.5%), moderate-to-high (48.0%), and high (15.5%) attentional function. Participants in the moderate class were significantly younger, with more comorbidities and lower functional status, than those in the other two classes. However, only functional status remained significant in multivariable models. Included in the genetic association analyses were 92 single nucleotide polymorphisms (SNPs) among 15 candidate genes. Additive, dominant, and recessive genetic models were assessed for each SNP. Controlling for functional status, only Interleukin 6 (IL6) rs1800795 remained a significant genotypic predictor of class membership in multivariable models. Each additional copy of the rare "G" allele was associated with a 4-fold increase in the odds of belonging to the lower attentional function class (95% confidence interval: [1.78, 8.92]; p = .001). Findings provide preliminary evidence of subgroups of individuals with distinct trajectories of attentional function and of a genetic association with an IL6 promoter polymorphism. © The Author(s) 2013.

Preoperative breast pain in women with breast cancer may result from a number of causes. Previous work from our team found that breast pain occurred in 28.2% of women (n = 398) who were about to undergo breast cancer surgery. The occurrence of preoperative breast pain was associated with a number of demographic and clinical characteristics, as well as variation in two cytokine genes. Given that ion channels regulate excitability of sensory neurons, we hypothesized that variations in potassium channel genes would be associated with preoperative breast pain in these patients. Therefore, in this study, we evaluated for associations between single-nucleotide polymorphisms and inferred haplotypes among 10 potassium channel genes and the occurrence of preoperative breast pain in patients scheduled to undergo breast cancer surgery. Multivariable logistic regression analyses were used to identify those genetic variations that were associated with the occurrence of preoperative breast pain while controlling for age and genomic estimates of and self-reported race/ethnicity. Variations in four potassium channel genes: (1) potassium voltage-gated channel, delayed rectifier, subfamily S, member 1 (KCNS1); (2) potassium inwardly rectifying channel, subfamily J, member 3 (KCNJ3); (3) KCNJ6; and (4) potassium channel, subfamily K, member 9 (KCNK9) were associated with the occurrence of breast pain. Findings from this study warrant replication in an independent sample of women who report breast pain following one or more breast biopsies.

Lymphedema (LE) is a frequent complication following breast cancer treatment. While progress is being made in the identification of phenotypic risk factors for the development of LE, little information is available on the molecular characterization of LE. The purpose of this study was to determine if variations in pro- and anti-inflammatory cytokine genes were associated with LE following breast cancer treatment.Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with (n=155) and without LE (n=387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease, and a higher number of lymph nodes removed. Genetic associations were identified for three genes (i.e., interleukin (IL4) 4 (rs2227284), IL 10 (rs1518111), and nuclear kappa factor beta 2 (NFKB2 (rs1056890)) associated with inflammatory responses.These genetic associations suggest a role for a number of pro- and anti-inflammatory genes in the development of LE following breast cancer treatment.

Purpose of the research: To attempt to replicate the associations found in our previous study of patients and family caregivers between interleukin 6 (IL6) and nuclear factor kappa beta 2 (NFKB2) and sleep disturbance and to identify additional genetic associations in a larger sample of patients with breast cancer. Methods and sample: Patients with breast cancer (n=398) were recruited prior to surgery and followed for six months. Patients completed a self-report measure of sleep disturbance and provided a blood sample for genomic analyses. Growth mixture modeling was used to identify distinct latent classes of patients with higher and lower levels of sleep disturbance. Key results: Patients who were younger and who had higher comorbidity and lower functional status were more likely to be in the high sustained sleep disturbance class. Variations in three cytokine genes (i.e., IL1 receptor 2 (IL1R2), IL13, NFKB2) predicted latent class membership. Conclusions: Polymorphisms in cytokine genes may partially explain inter-individual variability in sleep disturbance. Determination of high risk phenotypes and associated molecular markers may allow for earlier identification of patients at higher risk for developing sleep disturbance and lead to the development of more targeted clinical interventions. © 2013 Elsevier Ltd.

Persistent pain following breast cancer surgery is a significant clinical problem. Although immune mechanisms may play a role in the development and maintenance of persistent pain, few studies have evaluated for associations between persistent breast pain following breast cancer surgery and variations in cytokine genes. In this study, associations between previously identified extreme persistent breast pain phenotypes (ie, no pain vs severe pain) and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. In unadjusted analyses, the frequency of 13 SNPs and 3 haplotypes in 7 genes differed significantly between the no pain and severe pain classes. After adjustment for preoperative breast pain and the severity of average postoperative pain, 1 SNP (ie, interleukin [IL] 1 receptor 2 rs11674595) and 1 haplotype (ie, IL10 haplotype A8) were associated with pain group membership. These findings suggest a role for cytokine gene polymorphisms in the development of persistent breast pain following breast cancer surgery. Perspective This study evaluated for associations between cytokine gene variations and the severity of persistent breast pain in women following breast cancer surgery. Variations in 2 cytokine genes were associated with severe breast pain. The results suggest that cytokines play a role in the development of persistent postsurgical pain.

Subgroups of patients with breast cancer may be at greater risk for cytokine-induced changes in cognitive function after diagnosis and during treatment. The purposes of this study were to identify subgroups of patients with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) predictors of subgroup membership. Self-reported attentional function was evaluated in 397 patients with breast cancer using the Attentional Function Index before surgery and for six months after surgery (i.e., seven time points). Using growth mixture modeling, three attentional function latent classes were identified: High (41.6%), Moderate (25.4%), and Low-moderate (33.0%). Patients in the Low-moderate class were significantly younger than those in the High class, with more comorbidities and lower functional status than the other two classes. No differences were found among the classes in years of education, race/ethnicity, or other clinical characteristics. DNA was recovered from 302 patients' samples. Eighty-two single nucleotide polymorphisms among 15 candidate genes were included in the genetic association analyses. After controlling for age, comorbidities, functional status, and population stratification due to race/ethnicity, IL1R1 rs949963 remained a significant genotypic predictor of class membership in the multivariable model. Carrying the rare "A" allele (i.e., GA. +. AA) was associated with a twofold increase in the odds of belonging to a lower attentional function class (OR: 1.98; 95% CI: 1.18, 3.30; p=.009). Findings provide evidence of subgroups of women with breast cancer who report distinct trajectories of attentional function and of a genetic association between subgroup membership and an IL1R1 promoter polymorphism. © 2013 Elsevier Ltd.

Purpose of the research: To identify distinct latent classes of individuals based on ratings of morning and evening fatigue; evaluate for differences in phenotypic characteristics, as well as symptom and quality of life scores, among these latent classes; and evaluate for an overlap in morning and evening fatigue class membership. Patients and methods: In a sample of 167 oncology outpatients and 85 of their FCs, growth mixture modeling was used to identify distinct latent classes based on ratings of morning and evening fatigue obtained before, during, and after radiation therapy. Analyses of variance and Chi Square analyses were used to evaluate for differences among the morning and evening fatigue latent classes. Results: Three distinct latent classes for morning fatigue were identified. Participants in the High Morning Fatigue class (47%) were younger and had lower functional status. Three distinct latent classes for evening fatigue were identified. Participants in the High Evening Fatigue class (61%) were younger, more likely to be female, more likely to have children at home, and more likely to be a FC. Only 10.3% of participants were classified in both the Very Low Morning and Low Evening Fatigue classes and 41.3% were classified in both the High Morning and High Evening Fatigue classes. Conclusions: Different characteristics were associated with morning and evening fatigue, which suggests that morning and evening fatigue may be distinct but related symptoms. Additional research is needed to elucidate the mechanisms that may underlie diurnal variability in fatigue. © 2013 Elsevier Ltd.

Context Sleep disturbance is a problem for oncology patients. Objectives To evaluate how sleep disturbance and daytime sleepiness (DS) changed from before to six months following surgery and whether certain characteristics predicted initial levels and/or the trajectories of these parameters. Methods Patients (n=396) were enrolled prior to surgery and completed monthly assessments for six months following surgery. The General Sleep Disturbance Scale was used to assess sleep disturbance and DS. Using hierarchical linear modeling, demographic, clinical, symptom, and psychosocial adjustment characteristics were evaluated as predictors of initial levels and trajectories of sleep disturbance and DS. Results All seven General Sleep Disturbance Scale scores were above the cutoff for clinically meaningful levels of sleep disturbance. Lower performance status; higher comorbidity, attentional fatigue, and physical fatigue; and more severe hot flashes predicted higher preoperative levels of sleep disturbance. Higher levels of education predicted higher sleep disturbance scores over time. Higher levels of depressive symptoms predicted higher preoperative levels of sleep disturbance, which declined over time. Lower performance status; higher body mass index; higher fear of future diagnostic tests; not having had sentinel lymph node biopsy; having had an axillary lymph node dissection; and higher depression, physical fatigue, and attentional fatigue predicted higher DS prior to surgery. Higher levels of education, not working for pay, and not having undergone neo-adjuvant chemotherapy predicted higher DS scores over time. Conclusion Sleep disturbance is a persistent problem for patients with breast cancer. The effects of interventions that can address modifiable risk factors need to be evaluated.

The purposes of this study were to evaluate for differences in phenotypic and genotypic characteristics in women who did and did not develop lymphedema (LE) following breast cancer treatment. Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with (n = 155) and without LE (n = 387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease and a higher number of lymph nodes removed. Genetic associations were identified for four genes (i.e., lymphocyte cytosolic protein 2 (rs315721), neuropilin-2 (rs849530), protein tyrosine kinase (rs158689), vascular cell adhesion molecule 1 (rs3176861)) and three haplotypes (i.e., Forkhead box protein C2 (haplotype A03), neuropilin-2 (haplotype F03), vascular endothelial growth factor-C (haplotype B03)) involved in lymphangiogensis and angiogenesis. These genetic associations suggest a role for a number of lymphatic and angiogenic genes in the development of LE following breast cancer treatment. © 2013 Miaskowski et al.

Context. Radiation therapy (RT) is a common treatment for prostate cancer. Despite available research, prostate cancer patients report that information about side effects is their most important unmet need. Additional research is needed that focuses on specific dimensions of the patient's symptom experience. Objectives. The study's purposes were to evaluate the trajectories of occurrence, severity, and distress of the six most prevalent symptoms reported by patients undergoing RT for prostate cancer and the effects of selected demographic and clinical characteristics on these trajectories. Methods. Patients completed the Memorial Symptom Assessment Scale 11 times before, during, and after RT. For problems with urination, pain, lack of energy, feeling drowsy, difficulty sleeping, and diarrhea, the trajectories of occurrence, severity, and distress were evaluated using multilevel generalized linear models. Results. Across all three dimensions, pain, lack of energy, feeling drowsy, and difficulty sleeping followed a decreasing linear trend. Problems with urination and diarrhea demonstrated more complex patterns of change over time. Conclusion. Although longitudinal data on pain, lack of energy, feeling drowsy, and difficulty sleeping are limited, they are highly prevalent symptoms in these patients. In addition, diarrhea becomes a significant problem for these patients over the course of RT. A number of demographic and clinical characteristics affect the trajectories of these common symptoms differentially. © 2012 U.S. Cancer Pain Relief Committee.

The purpose of this study was to evaluate for differences in occurrence and severity ratings of sleep disturbance, fatigue, and decreased energy in women who reported breast pain prior to surgery for breast cancer. Of the 390 women who completed self-report measures for each symptom, 28.2% reported pain in their breast prior to surgery. A higher percentage of women in the pain group (i.e., 66.7% versus 53.5%) reported clinically meaningful levels of sleep disturbance. However, no between group differences were found in the severity of sleep disturbance, fatigue, or decreased energy. Findings from this study suggest that sleep disturbance, fatigue, and decreased levels of energy are significant problems for women prior to breast cancer surgery. Future studies need to evaluate for specific characteristics that place women at greater risk for these symptoms as well as the mechanisms that underlie these symptoms.

The purposes of this study were to determine the occurrence rate for preoperative breast pain; describe the characteristics of this pain; evaluate for differences in demographic and clinical characteristics; and evaluate for variations in pro- and anti-inflammatory cytokine genes between women who did and did not report pain. Patients (n = 398) were recruited prior to surgery and completed self-report questionnaires on a number of pain characteristics. Genotyping was done using a custom genotyping array. Women (28.2%) who reported breast pain were significantly younger (P