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BACKGROUND: Californias relatively low smoking rate (10.1% in 2019-2020) (About CHIS, UCLA Center for Health Policy Research, 2024) masks deep disparities among low-income populations, where smoking rates are nearly double that of their middle- to upper-income peers. Low-income smokers report a similar desire to quit and similar rates of recent quit attempts as smokers from other groups; yet, they often face barriers in accessing effective resources to facilitate successful cessation. METHODS: Our team will conduct a pragmatic stepped-wedge cluster, randomized controlled trial of Enhanced Multicomponent Proactive Navigator-Assisted Cessation of Tobacco Use (EMPACT-Us), a suite of tobacco cessation services supported by patient navigators, designed in close partnership with patients, providers, and community stakeholders. The study will take place at Family Health Centers of San Diego (FHCSD), the largest federally qualified health center (FQHC) in San Diego. Eight primary care clinics are included, where 70% (n = 13,496) of smokers at FHCSD receive care. DISCUSSION: We hypothesize that multiple points of engagement and integration of navigation services into the workflow of existing staff will improve utilization and cessation success. This study will examine if the enhanced suite of services offers insights on how to best integrate evidence-based tobacco treatment services into usual care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05750537, Registered on March 1, 2023. https://clinicaltrials.gov/study/NCT05750537 .

Background: In patients with lymphedema (LE), in addition to hand dominance, between-group comparisons of interlimb soft tissue differences need to account for differences in whole-body adiposity, measured directly by dual energy X-ray absorptiometry (DXA) or indirectly by body mass index. No study has evaluated the effects of hand dominance and whole-body adiposity on limb composition in patients with LE. This studys purpose was to compare soft tissue composition of affected and unaffected limbs of women with breast cancer, who did and did not have LE, controlling for dominance and percent body fat. Methods and Results: Whole-body DXA scans were acquired and included measures of percent body fat, upper limb total mass, upper limb fat mass, and upper limb fat-free mass. Participants were classified into one of three groups: women without LE; women with only subjective LE; and women with objective signs of LE at the time of assessment. Differences among the LE groups were evaluated using analysis of variance (ANOVA) and Chi-square analyses. Analysis of covariance (ANCOVA) was used to control for percent body fat and for the affected limb dominance. Compared to women without LE, women with objective signs of LE have greater total limb mass, fat mass, and fat-free mass in their affected limbs, independent of affected side dominance and percent body fat. In addition, the interlimb differences in total mass, fat mass, and fat-free mass were greater for the women with objective signs of LE, compared to the other two groups. Conclusions: DXA is useful in identifying soft tissue changes in patients with LE. Given that limb circumferences measure only changes in limb volume and that bioimpedance provides estimates of extracellular fluid, DXA has the advantage of being able to estimate the volumes of specific tissues in the limb.

Background: Lymphedema (LE) is a significant clinical problem for breast cancer survivors. While the water displacement test and circumferential assessment using a tape measure (TM) are common methods to assess differences in arm volumes, faster and more reliable methods are needed. Study purposes, in breast cancer survivors (n = 294), were to compare the average total arm volumes and interlimb volume ratios for women with and without a history of LE, using a TM and three-dimensional (3D), whole-body surface scanner (3D scan); compare the level of agreement between arm volumes and interlimb volume ratios obtained using the two devices; and evaluate the percent agreement between the two measures in classifying cases of LE using three accepted thresholds. Methods and Results: Measurements were done using a spring-loaded TM and Fit3D ProScanner. Paired t-tests and Bland-Altman analyses were used to achieve the study aims. For circumference and volume comparisons, compared with the 3D scan, values obtained using the TM were consistently smaller. In terms of level of agreement, the Bland-Altman analyses demonstrated large biases and wide limits of agreement for the calculated arm volumes and volume ratios. In terms of the classification of caseness, using the 200-mL interlimb volume difference criterion resulted in 81.6% overall agreement; using the >10% volume difference between the affected and unaffected arms resulted in 78.5% overall agreement; and using the volume ratio ≥1.04 criterion resulted in 62.5% overall agreement. For all three accepted threshold criteria, the percentage of cases was significantly different between the TM and 3D scan techniques. Conclusions: The 3D technology evaluated in this study has the potential to be used for self-initiated surveillance for LE. With improvements in landmark identification and software modifications, it is possible that accurate and reliable total arm volumes can be calculated and used for early detection.

Background: While supine bioimpedance devices are used to evaluate for lymphedema (LE), stand-on devices are gaining popularity. Because research on differences in bioimpedance values between the two devices is limited, this study's purposes were to: (1) determine the average upper limb impedance values and inter-limb ratios for women who self-reported having (n = 34) or not having (n = 61) a history of LE, using a single-frequency supine device and a multifrequency stand-on device; (2) compare the level of agreement in inter-limb impedance ratios between the two devices; evaluate the percent agreement between the two devices in classifying cases of LE using established supine thresholds; and evaluate the percent agreement in classifying cases of LE between the supine device using previously established supine thresholds and the stand-on device using two published standing thresholds. Methods and Results: Bioimpedance measures were done using the two devices. For the entire sample, absolute impedance values for both the affected and unaffected limbs were significantly higher for the stand-on device in women with and without LE. Impedance values for the two methods were highly correlated. Bland-Altman analysis determined that for the entire range of impedance ratios the values for the two devices could not be used interchangeably. Conclusions: Findings suggest that the stand-on device can be a useful and valid tool to assess for LE. However, because agreement is not perfect, values obtained from the two devices should not be used interchangeably to evaluate for changes in impedance ratios, particularly for ratios of >1.20.

The intestinal epithelium separates host tissue and gut-associated microbial communities. During inflammation, the host releases reactive oxygen and nitrogen species as an antimicrobial response. The impact of these radicals on gut microbes is incompletely understood. We discovered that the cryptic appBCX genes, predicted to encode a cytochrome bd-II oxidase, conferred a fitness advantage for E. coli in chemical and genetic models of non-infectious colitis. This fitness advantage was absent in mice that lacked epithelial NADPH oxidase 1 (NOX1) activity. In laboratory growth experiments, supplementation with exogenous hydrogen peroxide enhanced E. coli growth through AppBCX-mediated respiration in a catalase-dependent manner. We conclude that epithelial-derived reactive oxygen species are degraded in the gut lumen, which gives rise to molecular oxygen that supports the aerobic respiration of E. coli. This work illustrates how epithelial host responses intersect with gut microbial metabolism in the context of gut inflammation.

ContextAlthough approximately 75% of patients with breast cancer report changes in attentional function, little is known about how demographic, clinical, symptom, and psychosocial adjustment (e.g., coping) characteristics influence changes in the trajectories of attentional function over time.ObjectivesThis study evaluated interindividual variability in the trajectories of self-reported attentional function and determined which demographic, clinical, symptom, and psychosocial adjustment characteristics were associated with initial levels and with changes in attentional function from before through 12 months after breast cancer surgery.MethodsBefore surgery, 396 women were enrolled. Attentional Function Index (AFI) was completed before and nine times within the first 12 months after surgery. Hierarchical linear modeling was used to determine which characteristics were associated with initial levels and trajectories of attentional function.ResultsGiven an estimated preoperative AFI score of 6.53, for each additional month, the estimated linear rate of change in AFI score was an increase of 0.054 (P

BackgroundAlthough multiple co-occurring symptoms are a significant problem for cancer survivors, to the authors' knowledge little is known regarding the phenotypic characteristics associated with a higher symptom burden. The objectives of the current study were to evaluate the occurrence, severity, and distress associated with 32 symptoms and examine the phenotypic and stress characteristics associated with a higher symptom burden.MethodsA total of 623 cancer survivors completed a demographic questionnaire, as well as measures of functional status, comorbidity, and global (Perceived Stress Scale) and cancer-related (Impact of Event Scale-Revised) stress. The Memorial Symptom Assessment Scale was used to evaluate symptom burden. Multiple linear regression analysis was used to determine the phenotypic characteristics associated with a higher symptom burden.ResultsThe mean number of symptoms was 9.1 (±5.2). The most common, severe, and distressing symptoms were lack of energy, problems with sexual interest/activity, and hair loss, respectively. Poorer functional status, a higher level of comorbidity, and a history of smoking as well as higher Perceived Stress Scale and Impact of Event Scale-Revised scores were associated with a higher symptom burden. The overall model explained approximately 45.6% of the variance in symptom burden.ConclusionsAlthough cancer survivors report a high number of co-occurring symptoms of moderate severity and distress, in the current study, no disease or treatment characteristics were found to be associated with a higher symptom burden. Clinicians need to assess for general and disease-specific stressors and provide referrals for stress management interventions. Future studies need to examine the longitudinal relationships among symptom burden, functional status, and level of comorbidity, as well as the mechanisms that underlie the associations between stress and symptom burden.

Persistent arm pain is a common problem after breast cancer surgery. Little is known about genetic factors that contribute to this type of postsurgical pain. Study purpose was to explore associations between persistent arm pain phenotypes and genetic polymorphisms among 15 genes involved in catecholaminergic and serotonergic neurotransmission. Women (n = 398) rated the presence and intensity of arm pain monthly for 6 months after breast cancer surgery. Three distinct latent classes of patients were identified (ie, no arm pain [41.6%], mild arm pain (23.6%), and moderate arm pain (34.8%). Logistic regression analyses were used to evaluate for differences between genotype or haplotype frequencies and the persistent arm pain classes. Compared with the no arm pain class, 3 single nucleotide polymorphisms and 1 haplotype, in 4 genes, were associated with membership in the mild arm pain class: COMT rs4633, HTR2A haplotype B02 (composed of rs1923886 and rs7330636), HTR3A rs1985242, and TH rs2070762. Compared with the no arm pain class, 4 single nucleotide polymorphisms in 3 genes were associated with membership in the moderate arm pain class: COMT rs165656, HTR2A rs2770298 and rs9534511, and HTR3A rs1985242. Findings suggest that variations in catecholaminergic and serotonergic genes play a role in the development of persistent arm pain. PERSPECTIVE: Limited information is available on genetic factors that contribute to persistent arm pain after breast cancer surgery. Genetic polymorphisms in genes involved in catecholaminergic and serotonergic neurotransmission were associated with 2 persistent arm pain phenotypes. Findings may be used to identify patients are higher risk for this common pain condition.

ContextRecent, albeit, limited evidence suggests that body mass index (BMI) may be a modifiable risk factor to reduce the deleterious effects of chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors.ObjectivesTo evaluate for differences in demographic, clinical, pain, sensation, and balance characteristics among three BMI groups. We hypothesized that as BMI increased, survivors would report higher pain intensity scores and have significant decrements in measures of sensation and balance.MethodsA total of 416 survivors with CIPN were evaluated using subjective and objective measures of CIPN. Survivors were divided into three BMI groups (i.e., normal weight, overweight, and obese). Differences among the BMI groups were evaluated using parametric and nonparametric statistics.ResultsOf the 416 survivors, 45.4% were normal weight, 32.5% were overweight, and 22.1% were obese. Compared with the normal-weight group, survivors in the other two groups had lower functional status scores, a higher comorbidity burden, higher pain intensity scores, and higher interference scores. In addition, compared with the normal-weight group, survivors in the other two BMI groups had significantly worse balance scores.ConclusionOur findings support the hypothesis that as BMI increased, pain sensation and balance characteristics worsened. Our findings suggest that nutritional counseling as well as exercise and weight management programs in survivors with CIPN may improve these clinically important problems.

Given the paucity of information on local tissue water (LTW) in the upper extremity and trunk of women after breast cancer surgery, the purpose of this study was to compare tissue dielectric constant (TDC) values between the affected and unaffected sides of breast cancer survivors with and without upper extremity lymphoedema (LE). Differences in LTW were assessed using the TDC method for three sites in the upper limbs, three sites in the lateral thorax and two sites on the back. Additional measures included demographic and clinical characteristics, arm circumference and bioimpedance analysis. For the 112 survivors without LE, no differences in TDC values were found between the affected and unaffected sides for the first dorsal web space, ventral forearm and upper arm, and upper and lower back. Compared to the unaffected side, TDC values were significantly higher on the affected side for the upper, mid and lower lateral thorax. For the 78 survivors with LE, compared to the unaffected side, TDC was significantly higher on the affected side for all of the sites evaluated except the hand web space. Our findings support the use of the TDC method to detect differences in upper extremity and truncal oedema in survivors with LE following breast cancer treatment. Measurement of LTW may provide a useful method to determine truncal as well as extremity LE. The ability to detect early signs of truncal oedema may lead to pre-emptive interventions in breast cancer survivors.

ObjectivesNumbness associated with neuropathic pain suggests the loss of function in myelinated, large diameter sensory neurons. The purpose of this study was to examine the relationships between pain severity and subjective (ie, severity of numbness) and objective (ie, loss of light touch sensations, vibration thresholds) measures of loss of large fiber function in adult survivors with chemotherapy-induced peripheral neuropathy (CIPN, n=426) and breast cancer patients with persistent postsurgical pain (n=80).Material and methodsFor both samples, average pain and numbness were evaluated using a 0 to 10 numeric rating scale. Loss of light touch sensations in the hands and feet of patients with CIPN and in the upper arm of patients at 5 and 6 months following breast cancer surgery were assessed using Semmes Weinstein monofilaments. Loss of vibration in the hands and feet of patients with CIPN was assessed using a biothesiometer. Pearson Product Moment correlation coefficients were calculated between average pain and the number or percentage of sites with loss of light touch sensations, mean vibration thresholds, and the severity of numbness.ResultsFor both pain conditions, average pain scores were significantly correlated with objective measures of large fiber function (r=0.12 to 0.34; all P

ContextAlthough paclitaxel is one of the most commonly used drugs to treat breast, ovarian, and lung cancers, little is known about the impact of paclitaxel-induced peripheral neuropathy (PIPN) on cancer survivors.ObjectivesThe purposes of this study were to evaluate for differences in demographic and clinical characteristics as well as measures of sensation, balance, upper extremity function, perceived stress, symptom burden, and quality of life (QOL) between survivors who received paclitaxel and did (n = 153) and did not (n = 58) develop PIPN.MethodsPain characteristics associated with PIPN are described in detail. Both subjective and objective measures were used to evaluate the impact of PIPN.ResultsSurvivors with PIPN were significantly older, had a higher body mass index, and a worse comorbidity profile. The duration of PIPN was almost four years, and pain scores were in the moderate range. Compared with survivors without PIPN, survivors with PIPN had a higher number of upper and lower extremity sites that had lost light touch, cold, and pain sensations. Survivors with PIPN had worse upper extremity function, more problems with balance, a higher symptom burden, and higher levels of perceived stress. In addition, survivors with PIPN had worse QOL scores particularly in the domain of physical functioning.ConclusionThe findings from this large descriptive study are the first to document the impact of PIPN on survivors' symptom burden, functional status, and QOL.

ContextThe most common adverse effects from neurotoxic chemotherapy are chemotherapy-induced neuropathy (CIPN), hearing loss, and tinnitus. Although associations between perceived stress and persistent pain, hearing loss, and tinnitus are documented, no studies have examined these associations in cancer survivors who received neurotoxic chemotherapy.ObjectivesIn this cross-sectional study, we evaluated for associations between perceived stress and the occurrence of CIPN, hearing loss, and tinnitus, in 623 adult cancer survivors who received platinum and/or taxane compounds.MethodsSurvivors completed self-report measures of hearing loss, tinnitus, and perceived stress (i.e., Impact of Events Scale-Revised [IES-R]). Separate logistic regression analyses were done for each neurotoxicity to evaluate whether each of the IES-R subscale (i.e., intrusion, avoidance, hyperarousal) and total scores made a significant independent contribution to neurotoxicity group membership.ResultsOf the 623 survivors in this study, 68.4% had CIPN, 34.5% reported hearing loss, and 31.0% reported tinnitus. Older age, higher body mass index, poorer functional status, being born prematurely, cancer diagnosis, and higher intrusion (P = 0.013), hyperarousal (P = 0.014), and total (P = 0.047) IES-R scores were associated with CIPN. Older age, being male, poorer functional status, a worse comorbidity profile, and a higher IES-R hyperarousal (P = 0.007) score were associated with hearing loss. Being male, having less education, a worse comorbidity profile, and a higher IES-R hyperarousal (P = 0.029) score were associated with tinnitus.ConclusionThese findings suggest that increased levels of perceived stress are associated with the most common chemotherapy-induced neurotoxicities.

BackgroundBreast cancer treatments can change women's hormonal milieu and alter their symptom experience. Little is known about associations between menopausal status and menopausal symptoms in women with breast cancer before surgery.ObjectiveThe purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between premenopausal and postmenopausal women before breast cancer surgery.MethodsA total of 312 women with breast cancer completed the Menopausal Symptoms Scale, a self-report measure that evaluated the occurrence, severity, and distress of 46 common symptoms associated with menopause. Regression analyses were used to evaluate for between-group differences in these symptoms.ResultsOf the 312 patients enrolled, 37.4% (n = 116) were premenopausal, and 62.6% (n = 196) were postmenopausal. In the multivariate analysis that adjusted for 7 covariates, premenopausal patients reported higher occurrence rates for urinary frequency (P = .006) and reported lower occurrence rates for joint pain/stiffness (P = .011), difficulty falling asleep (P = .025), and vaginal dryness (P = .002). A significant interaction was found between age and menopausal status for hot flashes (P = .002), wake during the night (P = .025), and headache (P = .040).ConclusionRegardless of menopausal status, women reported high occurrence rates for several menopausal symptoms. Associations between some symptom occurrence rates and menopausal status depended on the patients' age.Implications for practiceAs part of a preoperative symptom assessment, clinicians need to consider a woman's menopausal status and salient demographic and clinical characteristics. The identification of women with a higher symptom burden will assist with more effective management.

BackgroundBreast cancer treatments can change women's hormonal milieu and alter their symptom experience. Little is known about associations between menopausal status and menopausal symptoms in women with breast cancer before surgery.ObjectiveThe purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between premenopausal and postmenopausal women before breast cancer surgery.MethodsA total of 312 women with breast cancer completed the Menopausal Symptoms Scale, a self-report measure that evaluated the occurrence, severity, and distress of 46 common symptoms associated with menopause. Regression analyses were used to evaluate for between-group differences in these symptoms.ResultsOf the 312 patients enrolled, 37.4% (n = 116) were premenopausal, and 62.6% (n = 196) were postmenopausal. In the multivariate analysis that adjusted for 7 covariates, premenopausal patients reported higher occurrence rates for urinary frequency (P = .006) and reported lower occurrence rates for joint pain/stiffness (P = .011), difficulty falling asleep (P = .025), and vaginal dryness (P = .002). A significant interaction was found between age and menopausal status for hot flashes (P = .002), wake during the night (P = .025), and headache (P = .040).ConclusionRegardless of menopausal status, women reported high occurrence rates for several menopausal symptoms. Associations between some symptom occurrence rates and menopausal status depended on the patients' age.Implications for practiceAs part of a preoperative symptom assessment, clinicians need to consider a woman's menopausal status and salient demographic and clinical characteristics. The identification of women with a higher symptom burden will assist with more effective management.

CONTEXT: Approximately 60% to 100% of women with breast cancer experience at least one menopausal-related symptom. Little is known about associations between menopausal status and symptoms in women 12 months after breast cancer surgery. OBJECTIVES: The purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between pre- and postmenopausal women 12 months after breast cancer surgery. METHODS: Women with breast cancer (n = 327) completed the Menopausal Symptoms Scale, which evaluated the occurrence, severity, and distress of 46 common menopausal-related symptoms. Regression analyses were used to evaluate between-group differences in the seven symptoms that occurred in 30% and more of the sample (i.e., hot flashes, night sweats, depression, daytime sweats, joint pain or stiffness, wake during the night, and numbness or tingling). RESULTS: Of the 327 patients with breast cancer, who completed the 12-month assessment, 35.2% were premenopausal and 64.8% were postmenopausal before surgery. In the conditional models, when significant interactions were found, the differences in symptom occurrence rates between pre- and postmenopausal patients depended on their age. CONCLUSION: Regardless of menopausal status, women reported relatively high occurrence rates for several menopausal symptoms. Associations between symptom occurrence rates and menopausal status depended on the patients age. During the development of a survivorship care plan, clinicians need to assess symptom burden within the context of a womans menopausal status and salient demographic and clinical characteristics. This approach will assist with the prescription of more effective interventions.

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

ContextApproximately 60% to 100% of women with breast cancer experience at least one menopausal-related symptom. Little is known about associations between menopausal status and symptoms in women 12 months after breast cancer surgery.ObjectivesThe purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between pre- and postmenopausal women 12 months after breast cancer surgery.MethodsWomen with breast cancer (n = 327) completed the Menopausal Symptoms Scale, which evaluated the occurrence, severity, and distress of 46 common menopausal-related symptoms. Regression analyses were used to evaluate between-group differences in the seven symptoms that occurred in 30% and more of the sample (i.e., hot flashes, night sweats, depression, daytime sweats, joint pain or stiffness, wake during the night, and numbness or tingling).ResultsOf the 327 patients with breast cancer, who completed the 12-month assessment, 35.2% were premenopausal and 64.8% were postmenopausal before surgery. In the conditional models, when significant interactions were found, the differences in symptom occurrence rates between pre- and postmenopausal patients depended on their age.ConclusionRegardless of menopausal status, women reported relatively high occurrence rates for several menopausal symptoms. Associations between symptom occurrence rates and menopausal status depended on the patient's age. During the development of a survivorship care plan, clinicians need to assess symptom burden within the context of a woman's menopausal status and salient demographic and clinical characteristics. This approach will assist with the prescription of more effective interventions.

ContextApproximately 60% to 100% of women with breast cancer experience at least one menopausal-related symptom. Little is known about associations between menopausal status and symptoms in women 12 months after breast cancer surgery.ObjectivesThe purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between pre- and postmenopausal women 12 months after breast cancer surgery.MethodsWomen with breast cancer (n = 327) completed the Menopausal Symptoms Scale, which evaluated the occurrence, severity, and distress of 46 common menopausal-related symptoms. Regression analyses were used to evaluate between-group differences in the seven symptoms that occurred in 30% and more of the sample (i.e., hot flashes, night sweats, depression, daytime sweats, joint pain or stiffness, wake during the night, and numbness or tingling).ResultsOf the 327 patients with breast cancer, who completed the 12-month assessment, 35.2% were premenopausal and 64.8% were postmenopausal before surgery. In the conditional models, when significant interactions were found, the differences in symptom occurrence rates between pre- and postmenopausal patients depended on their age.ConclusionRegardless of menopausal status, women reported relatively high occurrence rates for several menopausal symptoms. Associations between symptom occurrence rates and menopausal status depended on the patient's age. During the development of a survivorship care plan, clinicians need to assess symptom burden within the context of a woman's menopausal status and salient demographic and clinical characteristics. This approach will assist with the prescription of more effective interventions.

PurposeThe purpose of this study was to evaluate for differences in demographic, clinical, and pain characteristics, as well as measures of sensation, balance, perceived stress, symptom burden, and quality of life (QOL) among survivors who received neurotoxic chemotherapy (CTX) and who reported only chemotherapy-induced neuropathy (CIN, n = 217), CIN and hearing loss (CIN/HL, n = 69), or CIN, hearing loss, and tinnitus (CIN/HL/TIN, n = 85). We hypothesized that as the number of neurotoxicities increased, survivors would have worse outcomes.MethodsSurvivors were recruited from throughout the San Francisco Bay area. Survivors completed self-report questionnaires for pain and other symptoms, stress and QOL. Objective measures were assessed at an in person visit.ResultsCompared to survivors with only CIN, survivors with all three neurotoxicities were less likely to be female and less likely to report child care responsibilities. In addition, survivors with all three neurtoxicities had higher worst pain scores, greater loss of protective sensation, and worse timed get up and go scores. These survivors reported higher state anxiety and depression and poorer QOL. For some outcomes (e.g., longer duration of CIN, self-reported balance problems), significantly worse outcomes were found for the survivors with CIN/HL and CIN/HL/TIN compared to those with only CIN.ConclusionsOur findings suggest that compared to survivors with only CIN, survivors with CIN/HL/TIN are at increased risk for the most severe symptom burden, significant problems associated with sensory loss and changes in balance, as well as significant decrements in all aspects of QOL.

ObjectivesTo assess the feasibility, safety, and initial estimates of efficacy of a yoga program in postoperative care for women at high risk for breast cancer-related lymphedema (BCRL).DesignSingle-group pretest-post-test design.Settings/locationPatients were recruited from the University of California, San Francisco Carol Franc Buck Breast Care Center.SubjectsTwenty-one women were enrolled in the study. Women were >18 years of age, had undergone surgical treatment for breast cancer, and were at high risk for BCRL.InterventionThe women participated in an Ashtanga yoga intervention for 8 weeks. Sessions consisted of once/week instructor-led practice and once/week home practice. Particular attention was given to poses that emphasized upper body strength and flexibility, while avoiding significant time with the upper extremity (UE) in a dependent position.Outcome measuresUE volume was assessed through circumferential forearm measurement, which was converted to volume using the formula for a truncated cone. Range of motion (ROM) was assessed for the shoulders, elbows, and wrists, using a standard goniometer. UE strength was assessed for shoulder abduction, elbow flexion, wrist flexion, and grip using a dynamometer.ResultsTwenty women completed the yoga intervention, with 17 returning for final assessment. Mean age was 52 (±9.1) years and body mass index was 24.8 (±5.1) kg/m2. Postintervention, mean volume in the at-risk UE was slightly reduced (p = 0.397). ROM for shoulder flexion (p

ObjectivesTo assess the feasibility, safety, and initial estimates of efficacy of a yoga program in postoperative care for women at high risk for breast cancer-related lymphedema (BCRL).DesignSingle-group pretest-post-test design.Settings/locationPatients were recruited from the University of California, San Francisco Carol Franc Buck Breast Care Center.SubjectsTwenty-one women were enrolled in the study. Women were >18 years of age, had undergone surgical treatment for breast cancer, and were at high risk for BCRL.InterventionThe women participated in an Ashtanga yoga intervention for 8 weeks. Sessions consisted of once/week instructor-led practice and once/week home practice. Particular attention was given to poses that emphasized upper body strength and flexibility, while avoiding significant time with the upper extremity (UE) in a dependent position.Outcome measuresUE volume was assessed through circumferential forearm measurement, which was converted to volume using the formula for a truncated cone. Range of motion (ROM) was assessed for the shoulders, elbows, and wrists, using a standard goniometer. UE strength was assessed for shoulder abduction, elbow flexion, wrist flexion, and grip using a dynamometer.ResultsTwenty women completed the yoga intervention, with 17 returning for final assessment. Mean age was 52 (±9.1) years and body mass index was 24.8 (±5.1) kg/m2. Postintervention, mean volume in the at-risk UE was slightly reduced (p = 0.397). ROM for shoulder flexion (p

PURPOSE:Given the inter-relatedness among symptoms, research efforts are focused on an evaluation of symptom clusters. The purposes of this study were to evaluate for differences in the number and types of menopausal-related symptom clusters assessed prior to and at 12-months after surgery using ratings of occurrence and severity and to evaluate for changes in these symptom clusters over time. METHODS:Prior to and at 12 months after surgery, 392 women with breast cancer completed the Menopausal Symptoms Scale. Exploratory factor analyses were used to identify the symptom clusters. RESULTS:Of the 392 women evaluated, the mean number of symptoms (out of 46) was 13.2 (±8.5) at enrollment and 10.9 (±8.2) at 12 months after surgery. Using occurrence and severity, three symptom clusters were identified prior to surgery. Five symptom clusters were identified at 12 months following surgery. Two symptom clusters (i.e., pain/discomfort and hormonal) were relatively stable across both dimensions and time points. Two symptom clusters were relatively stable across both dimensions either prior to surgery (i.e., sleep/psychological/cognitive) or at 12 months after surgery (i.e., sleep). The other four clusters (i.e., irritability, psychological/cognitive, cognitive, psychological) were identified at one time point using a single dimension. CONCLUSIONS:While some menopausal-related symptom clusters were consistent across time and dimensions, the majority of symptoms clustered together differently depending on whether they were evaluated prior to or at 12 months after breast cancer surgery. An increased understanding of how symptom clusters change over time may assist clinicians to focus their symptom assessments and management strategies.

PURPOSE:Given the inter-relatedness among symptoms, research efforts are focused on an evaluation of symptom clusters. The purposes of this study were to evaluate for differences in the number and types of menopausal-related symptom clusters assessed prior to and at 12-months after surgery using ratings of occurrence and severity and to evaluate for changes in these symptom clusters over time. METHODS:Prior to and at 12 months after surgery, 392 women with breast cancer completed the Menopausal Symptoms Scale. Exploratory factor analyses were used to identify the symptom clusters. RESULTS:Of the 392 women evaluated, the mean number of symptoms (out of 46) was 13.2 (±8.5) at enrollment and 10.9 (±8.2) at 12 months after surgery. Using occurrence and severity, three symptom clusters were identified prior to surgery. Five symptom clusters were identified at 12 months following surgery. Two symptom clusters (i.e., pain/discomfort and hormonal) were relatively stable across both dimensions and time points. Two symptom clusters were relatively stable across both dimensions either prior to surgery (i.e., sleep/psychological/cognitive) or at 12 months after surgery (i.e., sleep). The other four clusters (i.e., irritability, psychological/cognitive, cognitive, psychological) were identified at one time point using a single dimension. CONCLUSIONS:While some menopausal-related symptom clusters were consistent across time and dimensions, the majority of symptoms clustered together differently depending on whether they were evaluated prior to or at 12 months after breast cancer surgery. An increased understanding of how symptom clusters change over time may assist clinicians to focus their symptom assessments and management strategies.

BackgroundPaclitaxel is one of the most commonly used drugs to treat breast cancer. Its major dose-limiting toxicity is paclitaxel-induced peripheral neuropathy (PIPN). PIPN persists into survivorship and has a negative impact on patient's mood, functional status, and quality of life. No interventions are available to treat PIPN. A critical barrier to the development of efficacious interventions is the lack of understanding of the mechanisms that underlie PIPN. Mitochondrial dysfunction has been evaluated in preclinical studies as a hypothesized mechanism for PIPN, but clinical data to support this hypothesis are limited. The purpose of this pilot study was to evaluate for differential gene expression and perturbed pathways between breast cancer survivors with and without PIPN.MethodsGene expression in peripheral blood was assayed using RNA-seq. Differentially expressed genes (DEG) and pathways associated with mitochondrial dysfunction were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN.ResultsBreast cancer survivors with PIPN were significantly older; more likely to be unemployed; reported lower alcohol use; had a higher body mass index and poorer functional status; and had a higher number of lower extremity sites with loss of light touch, cold, and pain sensations and higher vibration thresholds. No between-group differences were found in the cumulative dose of paclitaxel received or in the percentage of patients who had a dose reduction or delay due to PIPN. Five DEGs and nine perturbed pathways were associated with mitochondrial dysfunction related to oxidative stress, iron homeostasis, mitochondrial fission, apoptosis, and autophagy.ConclusionsThis study is the first to provide molecular evidence that a number of mitochondrial dysfunction mechanisms identified in preclinical models of various types of neuropathic pain including chemotherapy-induced peripheral neuropathy are found in breast cancer survivors with persistent PIPN and suggest genes for validation and as potential therapeutic targets.

BackgroundPaclitaxel is one of the most commonly used drugs to treat breast cancer. Its major dose-limiting toxicity is paclitaxel-induced peripheral neuropathy (PIPN). PIPN persists into survivorship and has a negative impact on patient's mood, functional status, and quality of life. No interventions are available to treat PIPN. A critical barrier to the development of efficacious interventions is the lack of understanding of the mechanisms that underlie PIPN. Mitochondrial dysfunction has been evaluated in preclinical studies as a hypothesized mechanism for PIPN, but clinical data to support this hypothesis are limited. The purpose of this pilot study was to evaluate for differential gene expression and perturbed pathways between breast cancer survivors with and without PIPN.MethodsGene expression in peripheral blood was assayed using RNA-seq. Differentially expressed genes (DEG) and pathways associated with mitochondrial dysfunction were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN.ResultsBreast cancer survivors with PIPN were significantly older; more likely to be unemployed; reported lower alcohol use; had a higher body mass index and poorer functional status; and had a higher number of lower extremity sites with loss of light touch, cold, and pain sensations and higher vibration thresholds. No between-group differences were found in the cumulative dose of paclitaxel received or in the percentage of patients who had a dose reduction or delay due to PIPN. Five DEGs and nine perturbed pathways were associated with mitochondrial dysfunction related to oxidative stress, iron homeostasis, mitochondrial fission, apoptosis, and autophagy.ConclusionsThis study is the first to provide molecular evidence that a number of mitochondrial dysfunction mechanisms identified in preclinical models of various types of neuropathic pain including chemotherapy-induced peripheral neuropathy are found in breast cancer survivors with persistent PIPN and suggest genes for validation and as potential therapeutic targets.

ContextEvidence suggests that chemotherapy-induced neuropathy (CIN) is a significant problem for cancer survivors. However, a detailed phenotypic characterization of CIN in cancer survivors is not available.ObjectivesTo evaluate between-group differences in demographic and clinical characteristics, as well as in measures of sensation, function, and postural control, in a sample of cancer survivors who received a platinum and/or a taxane-based CTX regimen and did (n = 426) and did not (n = 197) develop CIN.MethodsSurvivors completed self-report questionnaires and underwent objective testing (i.e., light touch, pain sensation, cold sensation, vibration, muscle strength, grip strength, Purdue Pegboard test, Timed Get Up and Go test, Fullerton Advanced Balance test). Parametric and nonparametric statistics were used to compare between-group differences in study outcomes.ResultsOf the 426 survivors with CIN, 4.9% had CIN only in their upper extremities, 27.0% only in their lower extremities, and 68.1% in both their upper and lower extremities. Demographic and clinical characteristics associated with CIN included the following: older age, lower annual income, higher body mass index, a higher level of comorbidity, being born prematurely, receipt of a higher cumulative dose of chemotherapy, and a poorer functional status. Survivors with CIN had worse outcomes for all of the following objective measures: light touch, pain, temperature, vibration, upper and lower extremity function, and balance.ConclusionsThis study is the first to provide a detailed phenotypic characterization of CIN in cancer survivors who received a platinum and/or a taxane compound. These data can serve as a benchmark for future studies of CIN in cancer survivors.

BackgroundPotassium (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).ObjectiveThe 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.MethodsUpper 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.ResultsPatients 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.DiscussionThese preliminary findings suggest that K channel genes play a role in the development of secondary LE.

Intestinal inflammation is frequently associated with an alteration of the gut microbiota, termed dysbiosis, which is characterized by a reduced abundance of obligate anaerobic bacteria and an expansion of facultative Proteobacteria such as commensal E. coli. The mechanisms enabling the outgrowth of Proteobacteria during inflammation are incompletely understood. Metagenomic sequencing revealed bacterial formate oxidation and aerobic respiration to be overrepresented metabolic pathways in a chemically induced murine model of colitis. Dysbiosis was accompanied by increased formate levels in the gut lumen. Formate was of microbial origin since no formate was detected in germ-free mice. Complementary studies using commensal E. coli strains as model organisms indicated that formate dehydrogenase and terminal oxidase genes provided a fitness advantage in murine models of colitis. In vivo, formate served as electron donor in conjunction with oxygen as the terminal electron acceptor. This work identifies bacterial formate oxidation and oxygen respiration as metabolic signatures for inflammation-associated dysbiosis.

ContextLittle is known about the phenotypic and molecular characteristics associated with changes over time in fatigue and lack of energy in patients with breast cancer.ObjectivesThe 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.MethodsPatients 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.ResultsFor 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.ConclusionWithin 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.

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.

PurposeApproximately 20 % of patients develop lymphedema (LE) following breast cancer (BC) surgery. An evaluation of distinct trajectories of volume change may improve our ability to diagnose LE sooner. The purposes of this study were to identify subgroups of women with distinct trajectories of limb volume changes following BC surgery and to evaluate for phenotypic differences among these classes.MethodsIn this prospective longitudinal study, 380 women were enrolled prior to unilateral BC surgery. Upper limb bioimpedance was measured preoperatively and serially for 1 year postoperatively. Resistance ratios (RRs) were calculated. A RR of >1 indicates affected limb volume > unaffected limb volume. Latent class growth analysis (LCGA) was used to identify classes of women with distinct postoperative RR trajectories. Differences among classes were evaluated using analyses of variance and chi-square analyses.ResultsThree distinct classes were identified as follows: RR 1.05 (15.3 %). Patients in the RR >1.05 class were more likely to have diabetes (p = 0.036), were more likely to have BC on their dominant side (p

Research on the effect of cardiorespiratory (CR) exercise on upper extremity (UE) limb volume is limited in women with breast cancer-related lymphedema (BCRL). The aim of this study was to compare changes in UE volume immediately following a symptom-limited CR treadmill test in women with and without BCRL. As part of a cross-sectional study, 133 women post unilateral BC treatment completed symptom-limited treadmill testing. Bioimpedance spectroscopy (BIS) was used to measure UE resistance before and immediately following treadmill testing. Resistance ratios >1 (unaffected side/affected side) indicate greater volume in the affected limb. T-tests and repeated measures ANOVA were performed to evaluate differences between and within groups. Mean age was 56.2 years (SD 9.4); BMI was 26.13 kg m(-2) (SD 5.04). For women with previously diagnosed BCRL (n = 63), the resistance ratio was 1.116 (SD 0.160) pre-treadmill and 1.108 (SD 0.155) post-treadmill. For women without BCRL (n = 70), the resistance ratio was 0.990 (SD 0.041) pre-treadmill and 1.001 (SD 0.044) post-treadmill. Resistance ratios for women with BCRL were higher than those for women without BCRL at both time points (main effect of group: p < 0.001). No main effects were found for time (p = 0.695). A statistically significant effect was found for the time-by-group interaction (p = 0.002). 78% of the women with BCRL wore a compression garment during testing. Following testing, the women with BCRL demonstrated a non-statistically significant decrease in the resistance ratio, suggesting an immediate decrease in interlimb volume difference. The women without BCRL demonstrated an increase in the resistance ratio.

BackgroundUnderstanding 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 resultsThis 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.ConclusionsPrior 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.

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.

Study designDescriptive, cross-sectional.IntroductionBreast cancer (BC) treatments place the nervous system at risk, which may contribute to upper extremity (UE) mechanosensitivity.Purpose of the studyTo evaluate elbow extension range of motion (EE-ROM) during upper limb neurodynamic testing (ULNT) post-BC treatment.MethodsULNT EE-ROM was measured for 145 women post-BC treatment. Women were sub-grouped by presence/absence of pain and lymphedema.ResultsMean EE-ROM during ULNT1 was -22.3° (SD 11.9°) on the unaffected limb and -25.99° (SD 13.1°) on the affected limb. The women with pain and lymphedema had the greatest limitation in EE-ROM during ULNT1 testing, particularly of their affected limb (-33.8°, SD 12.9). Symptoms were reported more frequently in the affected chest, shoulder, arm, elbow, and hand. The intensity of symptoms was greater at the affected chest (p = 0.046), shoulder (p = 0.033) and arm (p = 0.039).ConclusionsWomen with lymphedema and pain after BC treatment may present with altered neural mechanosensitivity.Level of evidence3a.

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.

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.

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.

IntroductionBreast-cancer-related lymphedema affects approximately 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 (R (2) 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.

IntroductionBreast-cancer-related lymphedema affects approximately 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 (R (2) 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.