Betty Smoot

Upper extremity impairments in women with or without lymphedema following breast cancer treatment

IntroductionBreast-cancer-related lymphedema affects ∼25% of breast cancer (BC) survivors and may impact use of the upper limb during activity. The purpose of this study is to compare upper extremity (UE) impairment and activity between women with and without lymphedema after BC treatment.Methods144 women post BC treatment completed demographic, symptom, and Disability of Arm-Shoulder-Hand (DASH) questionnaires. Objective measures included Purdue pegboard, finger-tapper, Semmes-Weinstein monofilaments, vibration perception threshold, strength, range of motion (ROM), and volume.ResultsWomen with lymphedema had more lymph nodes removed (p < .001), more UE symptoms (p < .001), higher BMI (p = .041), and higher DASH scores (greater limitation) (p < .001). For all participants there was less strength (elbow flexion, wrist flexion, grip), less shoulder ROM, and decreased sensation at the medial upper arm (p < .05) in the affected UE. These differences were greater in women with lymphedema, particularly in shoulder abduction ROM (p < .05). Women with lymphedema had bilaterally less elbow flexion strength and shoulder ROM (p < .05). Past diagnosis of lymphedema, grip strength, shoulder abduction ROM, and number of comorbidities contributed to the variance in DASH scores (R2 of 0.463, p < .001).Implications for cancer survivorsUE impairments are found in women following treatment for BC. Women with lymphedema have greater UE impairment and limitation in activities than women without. Many of these impairments are amenable to prevention measures or treatment, so early detection by health care providers is essential.

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.

Comparison of Diagnostic Accuracy of Clinical Measures of Breast Cancer-Related Lymphedema: Area Under the Curve

OBJECTIVE To compare diagnostic accuracy of measures of breast cancer-related lymphedema (BCRL). DESIGN Cross-sectional design comparing clinical measures with the criterion standard of previous diagnosis of BCRL. SETTING University of California San Francisco Translational Science Clinical Research Center. PARTICIPANTS Women older than 18 years and more than 6 months posttreatment for breast cancer (n=141; 70 with BCRL, 71 without BCRL). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Sensitivity, specificity, receiver operator characteristic curve, and area under the curve (AUC) were used to evaluate accuracy. RESULTS A total of 141 women were categorized as having (n=70) or not having (n=71) BCRL based on past diagnosis by a health care provider, which was used as the reference standard. Analyses of ROC curves for the continuous outcomes yielded AUC of .68 to .88 (P<.001); of the physical measures bioimpedance spectroscopy yielded the highest accuracy with an AUC of .88 (95% confidence interval, .80-.96) for women whose dominant arm was the affected arm. The lowest accuracy was found using the 2-cm diagnostic cutoff score to identify previously diagnosed BCRL (AUC, .54-.65). CONCLUSIONS Our findings support the use of bioimpedance spectroscopy in the assessment of existing BCRL. Refining diagnostic cutoff values may improve accuracy of diagnosis and warrant further investigation.

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.

Peripheral response to cervical or thoracic spinal manual therapy: an evidence-based review with meta analysis.

Abstract Objectives: Spinal manual therapy (SMT) is commonly used for treatment of musculoskeletal pain in the neck, upper back, or upper extremity. Some authors report a multi-system effect of SMT, including peripheral alterations in skin conductance and skin temperature, suggesting that SMT may initiate a sympathetic nervous system (SNS) response. The focus of this evidence-based review and meta-analysis is to evaluate the evidence of SNS responses and clinically relevant outcomes following SMT to the cervical or thoracic spine. Methods: A systematic search used the terms: ‘manual therapy’, ‘SMT’, ‘spinal manipulation’, ‘mobilization’, ‘SNS’, ‘autonomic nervous system’, ‘neurophysiology’, ‘hypoalgesia’, ‘pain pathophysiology’, ‘cervical vertebrae’, ‘thoracic vertebrae’, ‘upper extremity’, and ‘neurodynamic test’. Data were extracted and within-group and between-group effect sizes were calculated for outcomes of skin conductance, skin temperature, pain, and upper extremity range of motion (ROM) during upper limb neurodynamic tests (ULNTs). Results: Eleven studies were identified. Statistically significant changes were seen with increased skin conductance, decreased skin temperature, decreased pain, and increased upper extremity ROM during ULNT. Discussion: A mechanical stimulus at the cervical or thoracic spine can produce a SNS excitatory response (increased skin conductance and decreased skin temperature). Findings of reduced pain and increased ROM during ULNT provide support to the clinical relevance of SMT. This evidence points toward additional mechanisms underlying the therapeutic effect of SMT. The effect sizes are small to moderate and no long-term effects post-SMT were collected. Future research is needed to associate peripheral effects with a possible centrally-mediated response to SMT.

Polymorphisms in Cytokine Genes Are Associated With Higher Levels of Fatigue and Lower Levels of Energy in Women After Breast Cancer Surgery

CONTEXT Little is known about the phenotypic and molecular characteristics associated with changes over time in fatigue and lack of energy in patients with breast cancer. OBJECTIVES The aim of this study was to identify subgroups (i.e., latent classes) of women with distinct fatigue and energy trajectories; evaluate for differences in phenotypic characteristics between the latent classes for fatigue and energy; and evaluate for associations between polymorphisms in genes for pro- and anti-inflammatory cytokines, their receptors, and their transcriptional regulators and latent class membership. METHODS Patients were enrolled before and followed for six months after breast cancer surgery. Latent class analyses were done to identify subgroups of patients with distinct fatigue and energy trajectories. Candidate gene analyses were done to identify cytokine genes associated with these two symptoms. RESULTS For both fatigue and lack of energy, two distinct latent classes were identified. Phenotypic characteristics associated with the higher fatigue class were younger age, higher education, lower Karnofsky Performance Status score, higher comorbidity, higher number of lymph nodes removed, and receipt of chemotherapy (CTX). Polymorphisms in interleukin (IL) 1β and IL10 were associated with membership in the higher fatigue class. Phenotypic characteristics associated with the lower energy class included: a lower Karnofsky Performance Status score and a higher comorbidity score. A polymorphism in IL1R1 was associated with membership in the lower energy class. CONCLUSION Within each latent class, the severity of fatigue and decrements in energy were relatively stable over the first six months after breast cancer surgery. Distinct phenotypic characteristics and genetic polymorphisms were associated with membership in the higher fatigue and lower energy classes.

Impact of chemotherapy-induced neurotoxicities on adult cancer survivors’ symptom burden and quality of life

PurposeLimited information is available on the impact of chemotherapy (CTX)-induced neurotoxicity on adult survivors’ symptom experience and quality of life (QOL). Purposes were to describe occurrence of hearing loss and tinnitus and evaluate for differences in phenotypic characteristics and measures of sensation, balance, perceived stress, symptom burden, and QOL between survivors who received neurotoxic CTX and did (i.e., neurotoxicity group) and did not (i.e., no neurotoxicity group) develop neurotoxicity. Neurotoxicity was defined as the presence of chemotherapy-induced neuropathy (CIN), hearing loss, and tinnitus. Survivors in the no neurotoxicity group had none of these conditions.MethodsSurvivors (n = 609) completed questionnaires that evaluated hearing loss, tinnitus, stress, symptoms, and QOL. Objective measures of sensation and balance were evaluated.ResultsOf the 609 survivors evaluated, 68.6% did and 31.4% did not have CIN. Of the survivors without CIN, 42.4% reported either hearing loss and/or tinnitus and 48.1% of the survivors with CIN reported some form of ototoxicity. Compared to the no neurotoxicity group (n = 110), survivors in the neurotoxicity group (n = 85) were older, were less likely to be employed, had a higher comorbidity burden, and a higher symptom burden, higher levels of perceived stress, and poorer QOL (all p < .05).ConclusionsFindings suggest that CIN, hearing loss, and tinnitus are relatively common conditions in survivors who received neurotoxic CTX.Implications for cancer survivorsSurvivors need to be evaluated for these neurotoxicities and receive appropriate interventions. Referrals to audiologists and physical therapists are warranted to improve survivors’ hearing ability, functional status, and QOL.

Predictors of Altered Upper Extremity Function During the First Year After Breast Cancer Treatment.

ObjectiveThe purpose of this study was to evaluate trajectories of and predictors for changes in upper extremity (UE) function in women (n = 396) during the first year after breast cancer treatment. DesignProspective, longitudinal assessments of shoulder range of motion (ROM), grip strength, and perceived interference of function were performed before and for 1 year after surgery. Demographic, clinical, and treatment characteristics were evaluated as predictors of postoperative function. ResultsWomen had a mean (SD) age of 54.9 (11.6) years, and 64% were white. Small but statistically significant reductions in shoulder ROM were found on the affected side over 12 months (P < 0.001). Predictors of interindividual differences in ROM at the 1-month assessment were ethnicity, neoadjuvant chemotherapy, type of surgery, axillary lymph node dissection, and preoperative ROM. Predictors of interindividual differences in changes over time in postoperative ROM were living alone, type of surgery, axillary lymph node dissection, and adjuvant chemotherapy. Declines in mean grip strength from before through 1 month after surgery were small and not clinically meaningful. Women with greater preoperative breast pain interference scores had higher postoperative interference scores at all postoperative assessments. ConclusionSome of the modifiable risk factors identified in this study can be targeted for intervention to improve UE function in these women.

Breast Cancer Treatments and Complications: Implications for Rehabilitation

&NA; Breast cancer is the most common cancer in women. Following breast cancer treatment, a significant number of women will develop treatment‐related complications that affect function and quality of life. The complications are not always localized to the breast tissue, as many of the treatments have larger regional and systemic affects on body structures and function, including mental functions; neuromusculoskeletal and movement related functions and structures; and functions of the cardiovascular, hematologic, immunologic and respiratory systems. Many of these complications go unrecognized and few of these women are referred for rehabilitation. Here we detail the current clinical treatments for breast cancer, the cell biological responses to these treatments, and the immediate and long‐term effects of each treatment on physical function. With greater knowledge of the sequelae of breast cancer treatments, rehabilitation specialists will be better equipped to provide evidence based, informed, carefully directed, and beneficial care for patients with breast cancer.

Potassium Channel Candidate Genes Predict the Development of Secondary Lymphedema Following Breast Cancer Surgery

Background Potassium (K+) channels play an important role in lymph pump activity, lymph formation, lymph transport, and the functions of lymph nodes. No studies have examined the relationship between K+ channel candidate genes and the development of secondary lymphedema (LE). Objective The study purpose was to evaluate for differences in genotypic characteristics in women who did (n = 155) or did not (n = 387) develop upper extremity LE following breast cancer treatment based on an analysis of single-nucleotide polymorphisms (SNPs) and haplotypes in 10 K+ channel genes. Methods Upper extremity LE was diagnosed using bioimpedance resistance ratios. Logistic regression analyses were used to identify those SNPs and haplotypes that were associated with LE while controlling for relevant demographic, clinical, and genomic characteristics. Results Patients with LE had a higher body mass index, had a higher number of lymph nodes removed, had more advanced disease, received adjuvant chemotherapy, received radiation therapy, and were less likely to have undergone a sentinel lymph node biopsy. One SNP in a voltage-gated K+ channel gene (KCNA1 rs4766311), four in two inward-rectifying K+ channel genes (KCNJ3 rs1037091 and KCNJ6 rs2211845, rs991985, rs2836019), and one in a two-pore K+ channel gene (KCNK3 rs1662988) were associated with LE. Discussion These preliminary findings suggest that K+ channel genes play a role in the development of secondary LE.