Deborah Hamolsky

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

UNLABELLED Study purposes were to determine the prevalence of persistent pain in the breast; characterize distinct persistent pain classes using growth mixture modeling; and evaluate for differences among these pain classes in demographic, preoperative, intraoperative, and postoperative characteristics. In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the pain classes, were evaluated. Patients (n = 398) were recruited prior to surgery and followed for 6 months. Using growth mixture modeling, patients were classified into no (31.7%), mild (43.4%), moderate (13.3%), and severe (11.6%) pain groups based on ratings of worst breast pain. Differences in a number of demographic, preoperative, intraoperative, and postoperative characteristics differentiated among the pain classes. In addition, patients in the moderate and severe pain classes reported higher preoperative levels of depression, anxiety, and sleep disturbance than the no pain class. Findings suggest that approximately 25% of women experience significant and persistent levels of breast pain in the first 6 months following breast cancer surgery. PERSPECTIVE Persistent pain is a significant problem for 25% of women following surgery for breast cancer. Severe breast pain is associated with clinically meaningful decrements in functional status and quality of life.

Associations between pro- and anti-inflammatory cytokine genes and breast pain in women prior to breast cancer surgery.

UNLABELLED 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 < .001); more likely to be nonwhite (P = .032); reported significantly lower Karnofsky Performance Status scores (P = .008); were less likely to be postmenopausal (P = .012); and had undergone significantly more biopsies (P = .006). Carriers of the minor allele for a single nucleotide polymorphism in interleukin (IL)1-receptor 1 (IL1R1) (rs2110726) were less likely to report breast pain prior to surgery (P = .007). Carriers of the minor allele for a single nucleotide polymorphism in IL13 (rs1295686) were more likely to report breast pain prior to surgery (P = .019). Findings suggest that breast pain occurs in over a quarter of women who are about to undergo breast cancer surgery. Based on phenotypic and genotypic characteristics found, inflammatory mechanisms contribute to preoperative breast pain. PERSPECTIVE In women with breast cancer, preoperative pain may be associated with increases in inflammatory responses associated with an increased number of biopsies. In addition, differences in cytokine genes may contribute to this preoperative breast pain.

Lymphatic and Angiogenic Candidate Genes Predict the Development of Secondary Lymphedema following Breast Cancer Surgery

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.

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.

Case Report: Painful Peripheral Neuropathy Following Treatment With Docetaxel for Breast Cancer

Peripheral neuropathy is a common side effect of many chemotherapy agents. As many as 60% of patients receiving taxane therapy report symptoms such as numbness, tingling, burning, pain, and, in severe cases, weakness in a stocking and glove pattern. These symptoms are associated with problems in physical mobility and decreased quality of life, yet few articles in the literature discuss collaborative interdisciplinary assessment and treatment of this population. This article describes the care of a patient with diabetes and docetaxel-induced, painful peripheral neuropathy by a multidisciplinary team of nurses, physicians, and physical therapists. Because nurses are often the first clinicians to recognize symptoms of chemotherapy-induced peripheral neuropathy, they provide the essential coordination of care by appropriate medical and rehabilitative services. This case also raises important questions about the relationship between diabetes mellitus and persistent, painful peripheral neuropathy.

Associations between cytokine gene variations and severe persistent breast pain in women following breast cancer surgery.

UNLABELLED 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.

Associations between cytokine gene variations and self-reported sleep disturbance in women following breast cancer surgery

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.

Co-occurrence of anxiety and depressive symptoms following breast cancer surgery and its impact on quality of life

PURPOSE Little is known about the prevalence of combined anxiety and depressive symptoms (CADS) in breast cancer patients. Purpose was to evaluate for differences in demographic and clinical characteristics and quality of life (QOL) prior to breast cancer surgery among women classified into one of four distinct anxiety and/or depressive symptom groups. METHODS A total of 335 patients completed measures of anxiety and depressive symptoms and QOL prior to and for 6 months following breast cancer surgery. Growth Mixture Modelling (GMM) was used to identify subgroups of women with distinct trajectories of anxiety and depressive symptoms. These results were used to create four distinct anxiety and/or depressive symptom groups. Differences in demographic, clinical, and symptom characteristics, among these groups were evaluated using analyses of variance and Chi square analyses. RESULTS A total of 44.5% of patients were categorized with CADS. Women with CADS were younger, non-white, had lower performance status, received neoadjuvant or adjuvant chemotherapy, had greater difficulty dealing with their disease and treatment, and reported less support from others to meet their needs. These women had lower physical, psychological, social well-being, and total QOL scores. Higher levels of anxiety with or without subsyndromal depressive symptoms were associated with increased fears of recurrence, hopelessness, uncertainty, loss of control, and a decrease in life satisfaction. CONCLUSIONS Findings suggest that CADS occurs in a high percentage of women following breast cancer surgery and results in a poorer QOL. Assessments of anxiety and depressive symptoms are warranted prior to surgery for breast cancer.

Preoperative Breast Pain Predicts Persistent Breast Pain and Disability After Breast Cancer Surgery

CONTEXT Approximately 30% of the women report pain in the affected breast before breast cancer surgery. OBJECTIVES The purpose of this secondary analysis of our prospective study was to determine how women who experienced both preoperative and persistent postsurgical breast pain (n=107) differed from women who did not report preoperative breast pain and did (n=158) or did not (n=122) experience persistent postsurgical breast pain. METHODS Differences in demographic and clinical characteristics were evaluated. Linear mixed effects (LME) modeling was used to evaluate for group differences in symptom severity, function, sensation, and quality of life (QOL) over time. RESULTS Between-group differences in demographic and clinical characteristics as well as trajectories of shoulder function and QOL were identified. Women with both preoperative and persistent postsurgical breast pain were younger; were more likely to report swelling, strange sensations, hardness, and numbness in the affected breast before surgery; and were more likely to have reconstruction at the time of surgery. Women with both preoperative and persistent postsurgical breast pain had more biopsies in the prior year, more lymph nodes removed, and reported more severe acute postsurgical pain than women without preoperative breast pain. The LME modeling revealed significant group effects for most outcomes evaluated. Over the six months of the study, women with both preoperative and persistent postsurgical pain had persistently poorer shoulder flexion and physical well-being than women without preoperative breast pain. CONCLUSION Investigations of the etiology and molecular mechanisms of preoperative breast pain, as well as interventions for this high-risk group, are needed.

Differences in sleep disturbance, fatigue and energy levels between women with and without breast pain prior to breast cancer surgery

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.