Arm Volume Difference Research Articles

Relation Between Characteristics of Indocyanine Green Lymphography and Development of Breast Cancer-Related Lymphedema.

Background: Breast cancer-related lymphedema (BCRL) is a disabling and frequently occurring condition after treatment for breast cancer. Studying lymph anatomy by means of indocyanine green (ICG) lymphography is a promising tool to help better understand BCRL. The aim of this study is to investigate the relation between ICG lymphography characteristics and the risk of developing BCRL. Methods and Results: Patients scheduled for breast surgery with either unilateral axillary lymph node dissection or sentinel lymph node biopsy between November 2017 and May 2019 were included. Patients were assessed at baseline and up to 36 months postsurgery. BCRL was defined as an increase of ≥5% relative arm volume difference compared with the presurgical difference. In total, 128 patients were included. During 36 months of follow-up, 45 patients (35.2%) developed BCRL. The number of lymph vessels before surgery was not a statistically significant risk factor for developing BCRL (p = 0.8485). However, an increase in the number of lymph vessels compared with baseline was a significant protective factor for developing BCRL (odds ratio = 0.8). An increase of one lymph vessel corresponds to a 19% relative risk reduction of developing BCRL. The presence of lymph nodes at baseline and the change in the presence of lymph nodes compared with baseline were no predictors for the development of BCRL (p = 0.0986 and p = 0.8910, respectively). Conclusions: An increase in the number of lymph vessels visualized by ICG lymphography compared with baseline is a protective factor for developing BCRL. Therapies with the ability to increase the number of lymph vessels can thus possibly decrease the risk of developing BCRL.

Early Disturbance of Lymphatic Transport as a Risk Factor for the Development of Breast-Cancer-Related Lymphedema

Breast-cancer-related lymphedema (BCRL) is a frequently occurring and debilitating condition. When lymphedema is diagnosed late, treatment can be expected to be less effective. Lymphofluoroscopy can provide details about the superficial lymphatic architecture and can detect an early disturbance of lymphatic transport (i.e., dermal backflow) before the lymphedema is clinically visible. The main objective of this study is to investigate whether this early disturbance of lymphatic transport visualized by lymphofluoroscopy is a risk factor for the development of BCRL. All patients scheduled for unilateral breast cancer surgery with axillary lymph node dissection or sentinel node biopsy were considered. Patients were assessed at baseline and 1, 3, 6, 9, 12, 18, 24 and 36 months postoperatively. During each visit, a clinical assessment was performed to determine the volume difference between both arms and hands (through circumference measurements and water displacement). Clinical BCRL was defined as a ≥5% increase in relative arm volume difference compared to the baseline value. Variables related to (1) the disturbance of lymphatic transport (through lymphofluoroscopy), (2) the demographics and general health of the patient and (3) the breast cancer and treatment of the patient were collected. We included data of 118 patients in the present study. Thirty-eight patients (39.8%) developed BCRL. Early disturbance of lymphatic transport was identified as a risk factor for the development of clinical BCRL (HR 2.808). Breast-cancer- and treatment-related variables such as axillary lymph node dissection (ALND) (HR 15.127), tumor stage (HR 1.745), mastectomy (HR 0.186), number of positive lymph nodes (HR 1.121), number of removed lymph nodes (HR 1.055), radiotherapy of the axilla (HR 2.715), adjuvant taxanes (HR 3.220) and postsurgical complications (HR 2.590) were identified as significant risk factors for the development of BCRL. In the multivariate analysis, age and ALND were withheld as independent risk factors for the development of BCRL. Lymphofluoroscopy can identify an early disturbance of lymphatic transport after breast cancer treatment. Patients with an early disturbance of lymphatic transport are considered to be a high-risk group for the development of BCRL. This study also confirms that age and ALND are predictors for the development of BCRL. Therefore, a surveillance program of these patients with lymphofluoroscopy could be useful to identify lymphedema in subclinical stages.

Agreement Between Optoelectronic Volumetry and Circumferential Girth Measurements to Diagnose Lymphedema in Patients Submitted to Axillary Radical Lymphadenectomy for Treatment of Cutaneous Melanoma

Background: To assess the agreement between indirect and optoelectronic volumetries to diagnose lymphedema based on arm volume difference in patients with axillary lymph node dissection (ALND) for cutaneous melanoma. Methods and Results: Patients were assessed by circumferential girth measurements (truncated cone formula) to determine the upper limb volumes (indirect volumetry) and by optoelectronic volumetry (Perometer®) of affected and control limbs. A diagnosis of lymphedema on each measuring method was defined as an absolute volume difference >200 mL or a relative volume >10%. Forty-six patients with ALND were included. There were no significant differences between the volume means or the mean absolute or relative differences measured by each method. Good correlation was observed between the volume of upper limbs for both the left (r = 0.998) and right (r = 0.985) arms. As for the diagnosis of lymphedema, an absolute volume difference >200 mL determined a prevalence of 28% (13/46) of lymphedema by indirect volumetry and 35% (16/46) by optoelectronics volumetry. The crude diagnostic agreement was 93% with a kappa = 85% (agreement adjusted by chance) between methods. If a 10% increase in the relative volume difference between the arms was used as the diagnostic criterion, prevalence was 20% (9/46) and 22% (10/46), respectively. Conclusion: There is good agreement between perometry and circumferential girth measurements when classifying patients as having a difference between arm volumes >200 mL or 10%, the most frequently used cutoffs to diagnose lymphedema.

Health‐related quality of life outcomes for the LEAP study—CALGB 70305 (Alliance): A lymphedema prevention intervention trial for newly diagnosed breast cancer patients

Lymphedema is an adverse effect of breast cancer treatment that causes swelling and pain in the arm and hand. We tested 2 lymphedema prevention interventions and their impact on health-related quality of life (HRQOL) in a group-randomized trial at 38 cooperative group sites within the United States. Patients were recruited before breast surgery. Sites were randomly assigned to education-only (EO) lymphedema prevention or education plus exercise and physical therapy (LEAP). Lymphedema was defined as a ≥10% difference in arm volume at any time from baseline to 18 months postsurgery. HRQOL was assessed using the Functional Assessment of Cancer Therapy-Breast plus 4 lymphedema items (FACT-B+4). Longitudinal mixed model regression analysis, adjusting for key demographic and clinical variables, examined participants' HRQOL by intervention group and lymphedema status. A total of 547 patients (56% LEAP) were enrolled and completed HRQOL assessments. The results revealed no differences between the interventions in preventing lymphedema (P = .37) or HRQOL (FACT-B+4 total score; P = .8777). At 18 months, the presence of lymphedema was associated with HRQOL at borderline significance (P = .0825). However, African American patients reported greater lymphedema symptoms (P = .0002) and better emotional functioning (P = .0335) than patients of other races or ethnicities. Lower HRQOL during the intervention was associated with younger age (P ≤ .0001), Eastern Cooperative Oncology Group performance status >0 (P = .0002), ≥1 positive lymph nodes (P = .0009), having no education beyond high school (P < .0001), having undergone chemotherapy (P = .0242), and having had only axillary node dissection or sentinel node biopsy versus both (P = .0007). The tested interventions did not differ in preventing lymphedema or in HRQOL outcomes. African American women reported greater HRQOL impacts due to lymphedema symptoms than women of other races or ethnicities.

L-Dex, arm volume, and symptom trajectories 24 months after breast cancer surgery.

PurposeStudy objectives were to examine: (a) biomarker trajectories (change from presurgical baseline values of Lymphedema index (L‐Dex) units and arm volume difference) and symptom cluster scores 24 months after breast cancer surgery and (b) associations of these objective biomarkers and symptom cluster scores. Patient/treatment characteristics influencing trajectories were also evaluated.MethodsA secondary analysis of data from the published interim analysis of a randomized parent study was undertaken using trajectory analysis. Five hundred and eight participants included in the prior analysis with 24 months of postsurgical follow‐up were initially measured with bioelectric impedance spectroscopy (BIS) and tape measure (TM) and completed self‐report measures. Patients were reassessed postsurgery for continuing eligibility and then randomized to either BIS or TM groups and measured along with self‐report data at regular and optional* visits 3, 6,12,15*,18, 21*, and 24‐months.ResultsThree subclinical trajectories were identified for each biomarker (decreasing, stable, increasing) and symptom cluster scores (stable, slight increase/decrease, increasing). Subclinical lymphedema was identified throughout the 24‐month period by each biomarker. An L‐Dex increase at 15 months in the BIS group was noted. The self‐report sets demonstrated contingency coefficients of 0.20 (LSIDS‐A soft tissue, P = .031) and 0.19 (FACTB+4, P = .044) with the L‐Dex unit change trajectories.ConclusionsThese data support the need for long‐term (24 months) prospective surveillance with frequent assessments (every 3 months) at least 15 months after surgery. Statistically significant convergence of symptom cluster scores with L‐Dex unit change supports BIS as beneficial in the early identification of subclinical lymphedema.

Effects of weight reduction on the breast cancer-related lymphedema: A systematic review and meta-analysis

BackgroundObesity has long been considered a risk factor for breast cancer–related lymphedema (BCRL), but the benefits of weight reduction in managing BCRL have not been clearly established. ObjectiveTo evaluate the beneficial effects of weight loss interventions (WLIs) on the reduction and prevention of BCRL. MethodsWe conducted a systematic review and meta-analysis by searching the PubMed, Scopus, and Embase databases from their earliest record to October 1st, 2019. We included randomized and non-randomized controlled trials involving adult patients with a history of breast cancer, that compared WLI groups with no-WLI groups, and provided quantitative measurements of lymphedema. ResultsInitial literature search yielded 461 nonduplicate records. After exclusion based on title, abstract, and full-text review, four randomized controlled trials involving 460 participants were included for quantitative analysis. Our meta-analysis revealed a significant between-group mean difference (MD) regarding the volume of affected arm (MD = 244.7 mL, 95% confidence interval [CI]: 145.3–344.0) and volume of unaffected arm (MD = 234.5 mL, 95% CI: 146.9–322.1). However, a nonsignificant between-group MD of −0.07% (95% CI: 1.22–1.08) was observed regarding the interlimb volume difference at the end of the WLIs. ConclusionsIn patients with BCRL, WLIs are associated with decreased volume of the affected and unaffected arms but not with decreased severity of BCRL measured by interlimb difference in arm volume.

Assessment of Upper Extremity Swelling Among Breast Cancer Survivors with a Commercial Infrared Sensor.

Background: There are various methods of detecting and monitoring arm lymphedema after breast cancer (BC) treatment. Using volumetric measurements is the most common method performed clinically in the United States, and several techniques exist. Recently, the use of infrared cameras has been explored by several groups. This study shows the use of this technology and its ability to assess arm volume measurements comparable to the Perometer while being more inexpensive, having a smaller footprint in clinics, and being easy to use. Methods and Results: Seventy-three BC survivors were scanned with the Perometer and the Kinect IR system, and arm volumes of 146 arms were calculated using their respective algorithms. Good correlation in the arm volume (R-squared = 0.8799) and percent difference (R-squared range 0.6277-0.7098) in the ranges where lymphedema diagnosis is made, and good clinical agreement of lymphedema status based on commonly used thresholds were found between the two modalities. The Cohen's kappa coefficient indicates that based on a 10% arm volume difference, there was a fair agreement (κ = 0.2663), and based on a 200 mL difference, there was a moderate agreement (κ = 0.5475) between the clinical outcomes of these two modalities. The Bland-Altman analysis of volume differences indicated a bias of 6.016 mL; thus, only a minor correction factor is necessary between the two modalities. Conclusion: The Kinect IR system presented can be used clinically for arm volume measurements to detect and monitor patients at risk for or managing lymphedema.

Manual lymph drainage may not have a preventive effect on the development of breast cancer-related lymphoedema in the long term: a randomised trial.

What are the short-term and long-term preventive effects of manual lymph drainage (MLD), when used in addition to information and exercise therapy, on the development of lymphoedema after axillary dissection for breast cancer? Randomised controlled trial with concealed allocation, blinded assessors and intention-to-treat analysis. Adults undergoing unilateral dissection for breast cancer were recruited, with 79 allocated to the experimental group and 81 to the control group. The experimental group received guidelines about prevention of lymphoedema, exercise therapy and MLD. The control group received the same guidelines and exercise therapy, but no MLD. The interventions in both groups were delivered for 6 months. The primary outcome was cumulative incidence of arm lymphoedema defined in four ways (≥200ml,≥2cm,≥5%, and≥10% increase), which represent the difference in arm volume or circumference between the affected and healthy sides compared with the difference before surgery. Secondary outcomes included point prevalence of lymphoedema, change in arm volume difference, shoulder range of movement, quality of life and function. Incidence rates were comparable between experimental and control groups at all follow-up measurements. Sixty months after surgery, the cumulative incidence rate for the≥200ml definition was 35% for the experimental group versus 29% for the control group (RR 0.89, 95% CI 0.51 to 1.54, p=0.45); for the≥2cm definition 35% versus 38% (RR 0.93, 95% CI 0.59 to 1.45, p=0.73); for the≥5% definition 68% versus 53% (RR 1.28, 95% CI 0.97 to 1.69, p=0.08) and for the≥10% definition 28% versus 24% (RR 1.18, 95% CI 0.66 to 2.10, p=0.57). The secondary outcomes were comparable between the groups at most assessment points. Manual lymph drainage may not have a preventive effect on the development of breast cancer-related lymphoedema in the short and long term. Netherlands Trial Register NTR 1055. [Devoogdt N, Geraerts I, Van Kampen M, De Vrieze T, Vos L, Neven P, Vergote I, Christiaens M-R, Thomis S, De Groef A (2018) Manual lymph drainage may not have a preventive effect on the development of breast cancer-related lymphoedema in the long term: a randomised trial. Journal of Physiotherapy 64: 245-254].

Perometry versus simulated circumferential tape measurement for the detection of breast cancer-related lymphedema.

Despite increasing emphasis on screening and early intervention for breast cancer-related lymphedema (BCRL), there is marked heterogeneity in diagnostic methodology, including for volumetric measures. This retrospective study compared two volumetric modalities, perometry and simulated circumferential tape measurement (anatomic- and interval-based), for BCRL detection. Between 2005 and 2017, 287 female patients with unilateral breast cancer were prospectively screened for BCRL by perometry and the relative volume change (RVC) formula. Circumferential measurement was performed by sampling at five anatomic landmark-based points or 4-cm intervals from pairs of perometerarm diameter measurements. Volumetric conversion was by a frustum model. The Bland-Altman method was used to compare segmental volume differences. Confusion matrix analysis was performed for each circumferential measurement technique against perometry. Median follow-up was 34.7months over4 postoperative visits. There was no difference in total arm volume comparing any of the circumferential measurementtechniques to perometry. Landmark-based methods significantly underestimated upper arm volume (mean difference - 207mL [- 336, - 78 mL]) and overestimated forearm volume (mean difference + 170mL [+ 105, + 237mL]). Landmark-based methods had greater sensitivity and specificity compared to 4-cm interval methods for detection of both RVC ≥ 10 and 5-10%. Landmark-based methods were comparable to perometry for detection of RVC ≥ 10%, but sensitivity was only 63.2-66.7% for RVC 5-10%. This hypothesis-generating study suggested the superiority of anatomic landmark-based circumferential tape measurement compared to interval-based methods, while generating questions about the underestimation of upper arm volume and overestimation of forearm volume of circumferential tape measurement compared to perometry.

Changes in volume and incidence of lymphedema during and after treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) in patients with breast cancer

PurposesThe purposes of this study were to investigate the incidence of lymphedema in patients with breast cancer during and after adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC), to identify predictors for development of lymphedema, and to describe consequences in daily life in relation to lymphedema.MethodsThis is a prospective study with measurements before chemotherapy (T0), during chemotherapy before cycle 2 (T1), cycle 4 (T2), and 1 month after completion of treatment (T3). Volume change was monitored using tape measurements. Lymphedema was defined as ≥ 10% volume difference. Linear mixed-effect models were estimated to analyze differences in arm volume and consequences in daily life (total score and domain scores of the Lymph-International Classification of Functioning (ICF) questionnaire) over time and to identify treatment and patient characteristics as predictors for changes in volume.ResultsForty-eight patients completed all measurements. Volume did not change during TAC treatment. One month after treatment, volume was significantly increased compared to T0-T2, and 12 patients (25%) had developed lymphedema. Axillary lymph node dissection was associated with lymphedema (ES 2.9, 95% CI 0.02–5.7; p < 0.05). In patients with and without lymphedema, 1 month after completion (T3), the Lymph-ICF questionnaire showed significant limitations in physical function compared to T0-T2. In patients with lymphedema at T3, a significant association between volume and total score on the Lymph-ICF questionnaire on physical function and mobility activities was observed.ConclusionsOne month after treatment in 12 patients (25%), volume difference increased over 10%. Axillary lymph node dissection was predictive for development of lymphedema. All patients, but more patients with lymphedema, perceived difficulties in activities in daily life after treatment.

The efficacy of lymphaticovenular anastomosis in breast cancer-related lymphedema

IntroductionLymphedema can be a debilitating condition, causing a great decrease in a person’s quality of life (QoL). Treatment with lymphaticovenular anastomosis (LVA), in which an anastomosis is created between the lymphatic and venous system, may attenuate lymphedema symptoms and reduce swelling. In this study, we share the results using LVA to treat breast cancer-related lymphedema (BCRL) at our institution.Materials and methodsPatients were eligible for inclusion if they suffered from unilateral BCRL, if functional lymphatics were available, if compression therapy was used for at least 6 months, and if the follow-up was 12 months at minimum. Lymph vessel functionality was assessed preoperatively using indocyanine green (ICG). During surgery, 1–3 anastomoses were created and shunt patency was confirmed using ICG. Arm volumes were measured before surgery and at 6- and 12-month follow-up. QoL was measured before surgery and at 6-month follow-up. Arm volume differences between the healthy arm and affected arm were compared between the time points.ResultsTwenty-nine consecutive female patients with unilateral BCRL were included. The preoperative mean difference in arm volumes was 701 ± 435 ml (36.9%). This was reduced to 496 ± 302 ml (24.7%) at 6-month follow-up (p = 0.00). At 12-month follow-up, the mean difference in arm volume was 467 ± 303 ml (23.5%) (p = 0.02). The overall perceived QoL was increased from 5.8 ± 1.1 to 7.4 ± 0.7 (p = 0.00). The functionality score decreased from 2.2 to 1.8 (p = 0.00), the appearance score decreased from 2.6 to 1.9 (p = 0.00), the symptoms score decreased from 2.8 to 1.8 (p = 0.00), and the mood score decreased from 2.7 to 1.5 (p = 0.00). Fifteen patients (53.6%) were able to discontinue the use of compression garment.ConclusionTreatment with LVAs is effective in reducing arm volume difference in patients suffering from BCRL. Although no complete reduction of the edema was achieved at 12-month follow-up, the procedure significantly increased the patients’ QoL.

A randomized cross-over trial to detect differences in arm volume after low- and heavy-load resistance exercise among patients receiving adjuvant chemotherapy for breast cancer at risk for arm lymphedema: study protocol.

BackgroundIn an effort to reduce the risk of breast cancer-related arm lymphedema, patients are commonly advised to avoid heavy lifting, impacting activities of daily living and resistance exercise prescription. This advice lacks evidence, with no prospective studies investigating arm volume changes after resistance exercise with heavy loads in this population. The purpose of this study is to determine acute changes in arm volume after a session of low- and heavy-load resistance exercise among women undergoing adjuvant chemotherapy for breast cancer at risk for arm lymphedema.Methods/DesignThis is a randomized cross-over trial. Participants: Women receiving adjuvant chemotherapy for breast cancer who have undergone axillary lymph node dissection will be recruited from rehabilitation centers in the Copenhagen area. Intervention: Participants will be randomly assigned to engage in a low- (two sets of 15–20 repetition maximum) and heavy-load (three sets of 5–8 repetition maximum) upper-extremity resistance exercise session with a one week wash-out period between sessions. Outcome: Changes in extracellular fluid (L-Dex score) and arm volume (ml) will be assessed using bioimpedance spectroscopy and dual-energy x-ray absorptiometry, respectively. Symptom severity related to arm lymphedema will be determined using a visual analogue scale (heaviness, swelling, pain, tightness). Measurements will be taken immediately pre- and post-exercise, and 24- and 72-hours post-exercise. Sample size: A sample size of 20 participants was calculated based on changes in L-Dex scores between baseline and 72-hours post exercise sessions.DiscussionFindings from this study are relevant for exercise prescription guidelines, as well as recommendations regarding participating in activities of daily living for women following surgery for breast cancer and who may be at risk of developing arm lymphedema.Trial registrationCurrent Controlled Trials ISRCTN97332727. Registered 12 February 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2548-y) contains supplementary material, which is available to authorized users.

A longitudinal analysis of chronic arm morbidity following breast cancer surgery.

Arm morbidity (AM) arising from breast cancer (BC) treatment can detrimentally impact quality of life; often limiting a survivor's ability to participate in valued activities. The present study explored (a) the developmental time course of AM [restricted range of motion (ROM), pain, and arm volume changes], negative affect, and perceived disability in the immediate years post-surgery, and (b) the mediating role of perceived disability on the relationship between AM and negative affect over time. In this 5-year longitudinal study, BC survivors from four Canadian oncology clinics (n=431) completed five annual clinical assessments, where differences in ROM (shoulder abduction, external rotation) and arm volume between the affected and non-affected arm were measured. The profile of mood states (POMS), disability of arm, shoulder, hand, and McGill Pain Questionnaire-Short form were completed. Results from general linear modeling showed that AM, negative affect, and perceived disability were greatest 1-year post-surgery, declined, and with the exception of arm volume changes, were significantly lower 5years later. Negative affect was significantly associated with restrictions in shoulder abduction and external rotation (average r=-0.15; p<0.05) and present arm pain (average r=0.28, p<0.01) at most assessments. The mediating role of perceived disability on the relationship between AM and negative affect was statistically significant in a majority of assessments. Perceived disability is the underlying factor driving the relationship between AM and mood disturbance over time. Rehabilitative therapy to improve survivors' functional well-being might mitigate the negative impacts of AM on emotional health.

A Prospective Validation Study of Bioimpedance with Volume Displacement in Early-Stage Breast Cancer Patients at Risk for Lymphedema.

Although volume displacement (VD) is considered the gold standard for diagnosing breast cancer-related lymphedema, it is inconvenient. We compared bioimpedance (L-Dex) and VD measurements in a prospective cohort of breast cancer patients at risk for lymphedema. Between 2010 and 2014, a total of 223 breast cancer patients were enrolled. Following exclusions (n = 37), 186 received baseline VD and L-Dex; follow-up measurements were performed at 3-6 months intervals for 3 years. At each visit, patients fitted into one of three categories: normal (normal VD and L-Dex); abnormal L-Dex (L-Dex > 10 or increase in 10 from baseline and normal VD); or lymphedema (relative arm volume difference of >10 % by VD ± abnormal L-Dex). Change in L-Dex was plotted against change in VD; correlation was assessed using the Pearson correlation. At a median follow-up of 18.2 months, 152 patients were normal, 25 had an abnormal L-Dex, and 9 developed lymphedema without a prior L-Dex abnormality. Of the 25 abnormal L-Dex patients, 4 progressed to lymphedema, for a total of 13 patients with lymphedema. Evaluating all time points, 186 patients had 829 follow-up measurements. Sensitivity and specificity of L-Dex compared with VD were 75 and 93 %, respectively. There was no correlation between change in VD and change in L-Dex at 3 months (r = 0.31) or 6 months (r = 0.21). VD and bioimpedance demonstrated poor correlation with inconsistent overlap of measurements considered abnormal. Of patients with an abnormal L-Dex, few progressed to lymphedema; most patients with lymphedema did not have a prior L-Dex abnormality. Further studies are needed to understand the clinical significance of bioimpedance.

Yoga management of breast cancer-related lymphoedema: a randomised controlled pilot-trial.

BackgroundSecondary arm lymphoedema continues to affect at least 20% of women after treatment for breast cancer requiring lifelong professional treatment and self-management. The holistic practice of yoga may offer benefits as an adjunct self-management option. The aim of this small pilot trial was to gain preliminary data to determine the effect of yoga on women with stage one breast cancer-related lymphoedema (BCRL). This paper reports the results for the primary and secondary outcomes.MethodsParticipants were randomised, after baseline testing, to receive either an 8-week yoga intervention (n = 15), consisting of a weekly 90-minute teacher-led class and a 40-minute daily session delivered by DVD, or to a usual care wait-listed control group (n = 13). Primary outcome measures were: arm volume of lymphoedema measured by circumference and extra-cellular fluid measured by bioimpedance spectroscopy. Secondary outcome measures were: tissue induration measured by tonometry; levels of sensations, pain, fatigue, and their limiting effects all measured by a visual analogue scale (VAS) and quality of life based on the Lymphoedema Quality of Life Tool (LYMQOL). Measurements were conducted at baseline, week 8 (post-intervention) and week 12 (four weeks after cessation of the intervention).ResultsAt week 8, the intervention group had a greater decrease in tissue induration of the affected upper arm compared to the control group (p = 0.050), as well as a greater reduction in the symptom sub-scale for QOL (p = 0.038). There was no difference in arm volume of lymphoedema or extra-cellular fluid between groups at week 8; however, at week 12, arm volume increased more for the intervention group than the control group (p = 0.032).ConclusionsAn 8-week yoga intervention reduced tissue induration of the affected upper arm and decreased the QOL sub-scale of symptoms. Arm volume of lymphoedema and extra-cellular fluid did not increase. These benefits did not last on cessation of the intervention when arm volume of lymphoedema increased. Further research trials with a longer duration, higher levels of lymphoedema and larger numbers are warranted before definitive conclusions can be made.

Arm lymphoedema after axillary surgery in women with invasive breast cancer

The primary aim was to compare arm lymphoedema after sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) in women with node-negative and node-positive breast cancer. The secondary aim was to examine the potential association between self-reported and objectively measured arm lymphoedema. Women who had surgery during 1999-2004 for invasive breast cancer in four centres in Sweden were included. The study groups were defined by the axillary procedure performed and the presence of axillary metastases: SLNB alone, ALND without axillary metastases, and ALND with axillary metastases. Before surgery, and 1, 2 and 3 years after operation, arm volume was measured and a questionnaire regarding symptoms of arm lymphoedema was completed. A mixed model was used to determine the adjusted mean difference in arm volume between the study groups, and generalized estimating equations were employed to determine differences in self-reported arm lymphoedema. One hundred and forty women had SLNB alone, 125 had node-negative ALND and 155 node-positive ALND. Women who underwent SLNB had no increase in postoperative arm volume over time, whereas both ALND groups showed a significant increase. The risk of self-reported arm lymphoedema 1, 2 and 3 years after surgery was significantly lower in the SLNB group compared with that in both ALND groups. Three years after surgery there was a significant association between increased arm volume and self-reported symptoms of arm lymphoedema. SLNB is associated with a minimal risk of increased arm volume and few symptoms of arm lymphoedema, significantly less than after ALND, regardless of lymph node status.

The effect of a varied exercise program (VEP) on shoulder function and lymphedema (LE) in breast cancer survivors (BCs): A pilot study.

82 Background: A common physical sequel after adjuvant therapy is a decrease in shoulder movement of the upper-limb of the affected side and the development of LE. Resistance exercise is known to be safe and does not increase the risk of LE. The objective of this study is to evaluate the effect of a VEP on shoulder range of motion and upper-limb LE after adjuvant therapy in BCs. Methods: 22 BCs treated with surgery and adjuvant therapy were randomly assigned to the VEP (n=12) or the control (n=10). The VEP aimed at improving aerobic endurance, joint mobility and muscle strength. The frequency of the VEP was 2 times a week, during 3 months, with a total of 30 sessions. Primary endpoints included the range shoulder motion and arm volumes of both arms. The secondary outcome was quality of life (QoL) as measured by the EORTC QLQ-C30. All outcome measures were assessed at baseline and after 3 months. Results: After ending the VEP, in the exercise group, the movements such as abduction (p=0.04), external rotation (p=0.02), extension (p=0.03) and flexion (p=0.01) of the affected arm increased significantly but there was no change for internal rotation (0.27). No significant changes in arm volume (p=0.06) were found after 3 months compared to baseline, whereas the quality of life did improve significantly (p=0.01). After 3 months the range of motion of the shoulder of the affected arm (sum of abduction, external rotation, extension and flexion) in the exercise group tended to be better although this was not significant (p=0.50). The arm volume difference between the two groups was not significant (p=0.10) but it was for the QoL (p=0.02). Conclusions: A VEP lead to significant specific improvements in arm mobility compared to baseline. These BCs also compared favourably to the control cohort, but this was not significant. The study confirms that exercising the ipsilateral arm and shoulder has no detrimental effect on LE and has a positive impact on the QoL. Standard guidelines concerning physical therapy to ameliorate shoulder function and LE are not available. Additional patients will be enrolled to develop standard recommendations for physical therapy to improve shoulder and limb function in BCs.

15. How frequently is breast conservation possible after neoadjuvant chemotherapy in women with breast cancer – Overview of our surgical practice

15. How frequently is breast conservation possible after neoadjuvant chemotherapy in women with breast cancer – Overview of our surgical practice

Abstract P2-14-02: A Pilot Study of Vascular Endothelial Growth Factor Inhibition with Pazopanib in Patients (pts) with Lymphedema Following Breast Cancer Treatment

Abstract Purpose: Lymphedema is a significant long-term complication of primary therapy for breast cancer. VEGF has a major impact on vascular permeability and lymphangiogenesis. In a prior case control study, we found a significant increase in serum VEGF-C (median 6895 vs. 5349 pg/mL, p=0.0016) in women with lymphedema compared to women without lymphedema suggesting inhibition of VEGF-C as a potential therapeutic strategy. Methods: Pts with significant unilateral lymphedema were treated with pazopanib 800 mg/day continuously. Baseline assessments include arm volume, interstitial fluid pressure (IFP), extracellular fluid volume by lymphometer (ECF), quality of life (QOL) and plasma VEGF-C,-D, and R3. IFP was measured serially for 24 hours after the first treatment; arm volume, ECF, QOL, and plasma VEGF-C/D/R3 are assessed every 4 weeks. Results: Ten pts were enrolled. Median duration of lymphedema was 3.5 years (0.7-8.2) Median time since surgery was 5.1 years (1.0-14.2); median time since radiation (n=9) was 4.7 years (0.4-8.8). Complete IFP data are available in 7 pts. Baseline IFP was significantly higher in the affected compared to unaffected arm (mean 5.73 vs. -1.78 mmHg; p=0.0005). Mean IFP in the affected arm decreased an average of 76% 24 hours after initiation of pazopanib (5.73 vs. 1.56 mmHg; p=0.0061). Toxicity was greater than anticipated with grade 3 fatigue (n=3), arthralgia (n=2), and anorexia (n=1); three pts discontinued therapy prior to the first post-treatment assessment. Five pts met the definition of response with a ≥25% reduction in excess arm volume four weeks after initiating treatment. ECF significantly (p=0.014) decreased as well though the mean difference in excess arm volume did not significantly change (p=0.06). Conclusions: Preliminary data supports the hypothesis that VEGF plays a role in the development and/or persistence of lymphedema after local therapy for breast cancer. Pazopanib acutely decreases IFP, leading to a decrease in ECF and modest improvement in arm volume but results in significant toxicity at the dose used on this study. Subsequent studies will explore a lower dose of pazopanib in this population. This study was supported by the Breast Cancer Research Foundation with pazopanib supplied by GSK. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-02.

Arm lymphoedema in a cohort of breast cancer survivors 10 years after diagnosis

Introduction. Arm lymphoedema is a frequent complication after breast cancer treatment. Early diagnosis and treatment is considered important for successful management of breast cancer related arm lymphoedema (BCRL). The purpose was to identify BCRL incidence, time of onset, progression/regression and associated factors 10 years after breast cancer diagnosis. Material and methods. Two hundred and ninety two patients treated with axillary node dissection and radiotherapy were included in this retrospective study. A total of 111 diagnosed with BCRL (incidence 38.7%). Of these women 98 were followed for up to 10 years after BCRL diagnosis. Forty consecutive patients registered with no BCRL were included in the control group. BCRL was defined as an increase in arm volume difference ≥5% and an increased thickness of subcutis. Follow-up was performed twice a year, including assessment of lymphoedema relative volume (LRV) by water displacement method and compression treatment. Additional intensive treatment was given if LRV increased by more than 5% since the previous visit or exceeded 20% in total. Results. Mean LRV was 8.1 ±3.6% at diagnosis and 9.0±6.7% at last follow-up measurement (mean 48.9±39.2 months) with no significant difference. There was no difference in progression of LRV between groups with early versus late diagnosis (within or after 12 months postoperatively), small (5–<10%) versus large (≥10%) LRV at time of diagnosis, or regular (at least twice a year) versus non-regular treatment. More BCRL patients with large LRV at diagnosis (15.8%), exceeded LRV ≥20% during follow-up time, than patients with small LRV at diagnosis (10.1%). Conclusion. BCRL can be identified at an early stage both in regard to time of diagnosis after operation and to edema volume, and that edema volume can be kept at a low level for at least 10 years. Small LRV at time of diagnosis appears to be more important for minimizing the progression of LRV than time of diagnosis after operation.