Identification Of A Higher Risk Lymphedema Phenotype And Associations With Cytokine Gene Polymorphisms.

CONTEXT: Breast cancer-related lymphedema (BCRL) is chronic condition that occurs in 5% to 75% of women following treatment for breast cancer. However, little is known about the risk factors and mechanisms associated with a worse BCRL profile. OBJECTIVES: Identify distinct BCRL profiles in women with the condition (i.e., lower vs. higher risk phenotype) and evaluate for associations with pro- and anti-inflammatory genes. METHODS: Latent class profile analysis (LCPA) was used to identify the BCRL profiles using phenotypic characteristics evaluated prior to surgery. Candidate gene analyses were done to identify cytokine genes associated with the two BCRL profiles. RESULTS: Of the 155 patients evaluated, 35.5% (n = 55) were in the Lower and 64.5% (n = 100) were in the Higher Risk classes. Risk factors for membership in the Higher class included: lower functional status, having sentinel lymph node biopsy, axillary lymph node dissection, mastectomy, higher number of positive lymph nodes, and receipt of chemotherapy. Polymorphisms for interleukin (IL)1-beta and IL6 were associated with membership in the Higher Risk class. CONCLUSION: The readily available and clinically relevant phenotypic characteristics associated with a worse BCRL profile can be used by clinicians to identify higher risk patients. If confirmed, these characteristics can be tested in predictive risk models. In addition, the candidate gene findings may guide the development of mechanistically-based interventions to decrease the risk of BCRL.

Predictive factors of academic success in neuromusculoskeletal anatomy among doctor of physical therapy students.

Predictors of academic success in anatomy have been studied, but not in Doctor of Physical Therapy (DPT) students. The objectives of this study were to (1) explore predictors of academic success in a DPT anatomy course, (2) evaluate sex-based differences in the predictors of academic success and their influence on anatomy course grade, and (3) investigate the influence of the DPT anatomy course on visual-spatial ability. Forty-nine DPT students completed a demographic questionnaire, Learning and Study Strategies Inventory (LASSI), and Mental Rotations Test (MRT) before the ten-week anatomy course (MRT-1) and repeated the MRT at the end of the course (MRT-2). Anatomy course grade was determined based on quizzes and written and practical examinations. Multiple regression analysis showed significant associations between the predictor variables age (p = 0.010) and the LASSI anxiety subscale (p = 0.017), which measures anxiety coping, with the anatomy course grade. On the MRT-1, male DPT students attempted and correctly answered more questions than females (both, p < 0.0001). Female students had higher LASSI self-regulation and use of academic resources subscale scores (both, p < 0.05). In the 44 DPT students that completed the MRT-2, the number of correct and attempted responses increased following the anatomy course (p < 0.0001). Age and anxiety coping, but not sex, are predictors of anatomy course grades in DPT students. Mental rotations test scores improved following the anatomy course. The LASSI should be used in other cohorts to identify students with low anxiety subscale scores in order to provide targeted support.

Assessment of Arm Volume Using a Tape Measure Versus a 3D Optical Scanner in Survivors with Breast Cancer-Related Lymphedema.

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.

Use of Dual-Energy X-Ray Absorptiometry to Assess Soft Tissue Composition in Breast Cancer Survivors With and Without Lymphedema.

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 study's 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.

A Comparison of Supine Versus Stand-on Bioimpedance Devices to Assess Breast Cancer-Related Lymphedema.

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.

Assessment of local tissue water in the arms and trunk of breast cancer survivors with and without upper extremity lymphoedema.

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.

Differences in symptom clusters before and twelve months after breast cancer surgery.

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.

Influence of Menopausal Status on the Symptom Experience of Women Before Breast Cancer Surgery.

BACKGROUND: Breast 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. OBJECTIVE: The 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. METHODS: A 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. RESULTS: Of 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). CONCLUSION: Regardless 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 PRACTICE: As 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.

Menopausal-Related Symptoms in Women One Year After Breast Cancer Surgery.

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 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.

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.

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.