Cytokine Gene Polymorphisms Associated With Various Domains of Quality of Life in Women With Breast Cancer.

CONTEXT: Little is known about the phenotypic and molecular characteristics associated with various domains of quality of life (QOL) in women after breast cancer surgery. OBJECTIVES: In a sample of women with breast cancer (n = 398), purposes were as follows: to identify latent classes with distinct trajectories of QOL from before surgery through six months after 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 after breast cancer surgery. The genetic associations identified suggest that cytokine dysregulation influences QOL outcomes. However, specific QOL domains may be impacted by different cytokines.

Gender Differences in Predictors of Quality of Life at the Initiation of Radiation Therapy.

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.

Variations in potassium channel genes are associated with distinct trajectories of persistent breast pain after breast cancer surgery.

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.

Cytokine gene variations associated with trait and state anxiety in oncology patients and their family caregivers.

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.

Associations between cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression in patients prior to breast cancer surgery.

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.

Associations between catecholaminergic, GABAergic, and serotonergic genes and self-reported attentional function in oncology patients and their family caregivers.

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.

Trajectories of fear of recurrence in women with breast cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cytokine gene associations with self-report ratings of morning and evening fatigue in oncology patients and their family caregivers.

The purpose of this study was to evaluate for differences in variations in pro- and anti-inflammatory cytokine genes between participants who were classified as having low and high levels of morning and evening fatigue and to evaluate for differences in phenotypic characteristics between these two groups. In a sample of 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their family caregivers, growth mixture modeling was used to identify latent classes of individuals based on ratings of morning and evening fatigue obtained prior to, during, and for 4 months following completion of radiation therapy. Differences in single nucleotide polymorphisms and haplotypes in 15 cytokine genes were evaluated between the latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on morning and evening fatigue class membership. Associations were found between morning fatigue and number of comorbidities as well as variations in tumor necrosis factor alpha (TNFA) rs1800629 and rs3093662. Evening fatigue was associated with caring for children at home and variations in interleukin 4 (IL4) rs2243248 and TNFA rs2229094. Younger age and lower performance status were associated with both morning and evening fatigue. These findings suggest that inflammatory mediators are associated with the development of morning and evening fatigue. However, because different phenotypic characteristics and genomic markers are associated with diurnal variations in fatigue, morning and evening fatigue may be distinct but related symptoms.

Persistent arm pain is distinct from persistent breast pain following breast cancer surgery.

UNLABELLED: Persistent 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. PERSPECTIVE: For 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.

Persistent breast pain following breast cancer surgery is associated with persistent sensory changes, pain interference, and functional impairments.

UNLABELLED: Interindividual 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. PERSPECTIVE: Subgroups 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.

Trajectories of Depressive Symptoms in Women Prior to and for Six Months After Breast Cancer Surgery.

Depressive symptoms are common in women with breast cancer. This study evaluated how ratings of depressive symptoms changed from the time of the preoperative assessment to 6 months after surgery and investigated whether specific demographic, clinical, and symptom characteristics predicted preoperative levels of and/or characteristics of the trajectories of depressive symptoms. Characteristics that predicted higher preoperative levels of depressive symptoms included being married/partnered; receipt of adjuvant chemotherapy; more fear of metastasis; higher levels of trait anxiety, state anxiety, sleep disturbance, problems with changes in appetite; more hours per day in pain; and lower levels of attentional function. Future studies need to evaluate associations between anxiety, fears of recurrence, and uncertainty, as well as personality characteristics and depressive symptoms.

Evidence of associations between cytokine gene polymorphisms and quality of life in patients with cancer and their family caregivers.

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.

Side of cancer does not influence limb volumes in women prior to breast cancer surgery.

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 10 cm 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.

Disease and treatment characteristics do not predict symptom occurrence profiles in oncology outpatients receiving chemotherapy.

BACKGROUND: A large amount of interindividual variability exists in the occurrence of symptoms in patients receiving chemotherapy (CTX). The purposes of the current study, which was performed in a sample of 582 oncology outpatients who were receiving CTX, were to identify subgroups of patients based on their distinct experiences with 25 commonly occurring symptoms and to identify demographic and clinical characteristics associated with subgroup membership. In addition, differences in quality of life outcomes were evaluated. METHODS: Oncology outpatients with breast, gastrointestinal, gynecological, or lung cancer completed the Memorial Symptom Assessment Scale before their next cycle of CTX. Latent class analysis was used to identify subgroups of patients with distinct symptom experiences. RESULTS: Three distinct subgroups of patients were identified (ie, 36.1% in Low class; 50.0% in Moderate class, and 13.9% in All High class). Patients in the All High class were significantly younger and more likely to be female and nonwhite, and had lower levels of social support, lower socioeconomic status, poorer functional status, and a higher level of comorbidity. CONCLUSIONS: Findings from the current study support the clinical observation that some oncology patients experience a differentially higher symptom burden during CTX. These high-risk patients experience significant decrements in quality of life.

Pain medication management processes used by oncology outpatients and family caregivers part II: home and lifestyle contexts.

CONTEXT: Despite 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. OBJECTIVES: To 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. METHODS: This 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. RESULTS: Home 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. CONCLUSION: Pain 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.

Pain medication management processes used by oncology outpatients and family caregivers part I: health systems contexts.

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.

Cytokine gene variations associated with subsyndromal depressive symptoms in patients with breast cancer.

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.

Predictors of initial levels and trajectories of anxiety in women before and for 6 months after breast cancer surgery.

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.

Cytokine candidate genes predict the development of secondary lymphedema following breast cancer surgery.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: These genetic associations suggest a role for a number of pro- and anti-inflammatory genes in the development of LE following breast cancer treatment.

Identification of patient subgroups and risk factors for persistent arm/shoulder pain following breast cancer surgery.

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.