Impact of neoadjuvant chemotherapy on breast cancer-related lymphedema after axillary lymph node dissection: a retrospective cohort study.

PURPOSE: We aimed to evaluate whether neoadjuvant chemotherapy (NAC) could be a risk factor for breast cancer-related lymphedema (BCRL) associated with axillary lymph node dissection (ALND). PATIENTS AND METHODS: A total of 596 patients with cT0-4N0-3M0 breast cancer who underwent ALND and chemotherapy were retrospectively analyzed between March 2012 and March 2022. NAC was administered in 188 patients (31.5%), while up-front surgery in 408 (68.5%). Univariate and multivariable Cox regression analyses were performed to determine whether NAC was an independent risk factor for BCRL. With propensity score matching (PSM), the NAC group and up-front surgery group were matched 1:1 by age, body mass index (BMI), molecular subtypes, type of breast surgery, and the number of positive lymph nodes. Kaplan-Meier survival analyses were performed for BCRL between groups before and after PSM. Subgroup analyses were conducted to explore whether NAC differed for BCRL occurrence in people with different characteristics. RESULTS: At a median follow-up of 36.3 months, 130 patients (21.8%) experienced BCRL [NAC, 50/188 (26.60%) vs. up-front surgery, 80/408 (19.61%); P = 0.030]. Multivariable analysis identified that NAC [hazard ratio, 1.503; 95% CI (1.03, 2.19); P = 0.033] was an independent risk factor for BCRL. In addition, the hormone receptor-negative/human epidermal growth factor receptor 2-negative (HR-/HER2-) subtype, breast-conserving surgery (BCS), and increased positive lymph nodes significantly increased BCRL risk. After PSM, NAC remained a risk factor for BCRL [hazard ratio, 1.896; 95% CI (1.18, 3.04); P = 0.007]. Subgroup analyses showed that NAC had a consistent BCRL risk in most clinical subgroups. CONCLUSION: NAC receipt has a statistically significant increase in BCRL risk in patients with ALND. These patients should be closely monitored and may benefit from early BCRL intervention.

Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema.

BACKGROUND: Lymphedema is a common problem after breast cancer treatment. Lymfactin® is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels. METHODS: Lymfactin® was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up. RESULTS: Fifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 1010 viral particles (vp)), and 12 patients received a higher dose (1 × 1011 vp) of Lymfactin®, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life. CONCLUSIONS: During 24 months' of follow-up, the results indicate that Lymfactin® is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.

Invention and Clinical Application of an Oversleeve for Measuring Limb Volume in Postoperative Breast Cancer Patients.

BACKGROUND: Lymphedema is a common complication of breast cancer treatment, affecting 1/5 of breast cancer survivors, but there is no reliable way to detect subclinical lymphedema. OBJECTIVE: The purpose of this study was to determine the feasibility and reliability of using an oversleeve as a postoperative limb volume measurement tool in breast cancer patients. METHODS: Fifty patients were analyzed based on inclusion criteria. A body volume measurement kit was designed based on the drainage volume method and the circumference measurement method. Twenty-two normal healthy people were measured by the drainage volume (LV) and oversleeve measuring limb volume (OMLV) methods, so as to verify the accuracy of OMLV. Twenty-eight patients with lymphedema diagnosed by the circumdiameter measurement (CDM) method were measured with OMLV for comparison. The difference in measurements between OMLV and CDM was compared in 50 patients with early lymphedema diagnosed by the LV method. RESULTS: There was no significant difference between the sleeve method and the drainage volume method in the normal population (P = 0.74). All patients with lymphedema diagnosed by CDM met the diagnostic criteria by the OMLV method. In patients with early lymphedema diagnosed by LV, the diagnostic rate with OMLV was significantly higher than that with CDM (P = 0.008). CONCLUSION: Similar to LV in the diagnosis of lymphedema, OMLV can effectively improve the diagnostic rate of early lymphedema, providing a new option for the diagnosis and treatment of lymphedema.

Feasibility of segmental bioelectrical impedance analysis for mild- to moderate-degree breast cancer-related lymphedema: Correlation with circumferential volume measurement and phase angle.

ABSTRACT: Segmental multi-frequency bioelectrical impedance analysis (s-MFBIA) has been adopted recently to evaluate the volume of breast cancer-related lymphedema (BCRL). This procedure uses the segmental phase angle (s-PhA) as an indicator of cellular integrity. In the smaller-built Asian population, the BCRL often has a small volume difference and can be overlooked by tape circumference volume measurement (TVM). This study aimed to investigate the clinical feasibility of s-MFBIA for the assessment of lymphedema severity compared with TVM and evaluate the association between lymphedema severity and cellular integrity of the affected arm based on s-PhA values for a patient with mild- to moderate-degree BCRL.Segmental PhA and extracellular water (ECW)/total body water (TBW) ratio of bilateral arms were measured using InBody S10, an s-MFBIA device, in 128 BCRL patients. Inter-limb volume ratio was measured using TVM. The inter-limb ECW/TBW ratio was correlated with inter-limb volume ratio. Inter-limb ECW/TBW ratio and inter-limb volume ratio were then correlated with inter-limb PhA ratio to demonstrate the association between lymphedema severity and arm cellular integrity.The inter-limb ECW/TBW ratio and inter-limb volume ratio were positively correlated (r = 0.654, P < .001). The same result was obtained after adjusting for age, body mass index, postoperative survival, and duration of lymphedema (r = 0.636, 0.653, 0.652, and 0.648, P < .001). The inter-limb PhA ratio demonstrated significant negative correlation with inter-limb ECW/TBW ratio and inter-limb volume ratio (r = -0.896, -0.562, P < .001).s-MFBIA has high consistency with the conventional TVM method, and its relation to cellular integrity by segmental PhA enables better understanding of the cellular state of the affected limb in mild- to moderate-degree BCRL. Therefore, it is clinically feasible for severity assessment and monitoring of mild- to moderate-degree BCRL in smaller-built Asian patients.

Reverse Lymph Node Mapping Using Indocyanine Green Lymphography: A Step Forward in Minimizing Donor-Site Morbidity in Vascularized Lymph Node Transfer.

BACKGROUND: Reverse lymphatic mapping before harvesting a lymph node flap is crucial to avoid donor-site lymphedema; however, the technique is complex and unavailable in many centers. The authors introduce radioisotope-free reverse lymphatic mapping using indocyanine green and Patent Blue dye. METHODS: The authors conducted a prospective study in patients undergoing free vascularized groin lymph node transfer for postmastectomy upper extremity lymphedema. The day before surgery, 0.2 ml of technetium-99 was injected into the first and second web spaces of the ipsilateral foot. The following day, once the patient was anesthetized, indocyanine green was injected into the same web spaces of the same foot and Patent Blue dye was injected just proximal to the upper margin of the skin paddle of the lymph node flap. The main lymph nodes draining the limb were localized using indocyanine green lymphography and gamma probe. RESULTS: Thirty-nine patients underwent vascularized groin lymph node transfer with or without deep inferior epigastric artery perforator flap breast reconstruction. Navigation of the main lower extremity draining inguinal lymph nodes using the gamma probe and indocyanine green lymphography was identical in all patients. The blue-stained lymphatics in the skin paddle drained to the superficial proximal inguinal lymph node and were targeted for transfer. No donor-site lymphedema was reported, and lymphatic drainage of the lower extremity was preserved in all cases. CONCLUSIONS: Reverse lymphatic mapping using indocyanine green lymphography provides identical results to those using technetium-99 isotope scanning. However, indocyanine green is preferable in terms of safety and reproducibility and also avoids the complexity and hazards of radioisotope mapping. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Patients who report cording after breast cancer surgery are at higher risk of lymphedema: Results from a large prospective screening cohort.

OBJECTIVES: To identify the association between cording and breast cancer-related lymphedema (BCRL); describe time course, location, symptoms and functional impairments. METHODS: A total of 1181 patients were prospectively screened for BCRL after breast cancer (BC) surgery, including patient-reported outcome measures (4193) and perometric arm volume measurements (BCRL defined as relative or weight-adjusted volume change [RVC or WAC] ≥10% ≥3 months postoperatively). RESULTS: A total of 374/1181 patients (31.7%) reported cording first a median of 4.5 months postoperatively, and were more likely to: have body mass index less than 30 kg/m2 ; be less than 55 years of age; have had mastectomy, axillary lymph node dissection, regional lymph node radiation, neoadjuvant chemotherapy (all P < .001), or RVC/WAC ≥10% (P = .002). Patients who reported cording had 2.4 times the odds of developing BCRL compared to those who did not (odds ratio = 2.40; 95% confidence interval = 1.40-4.11; P = .002), and most frequently reported these symptoms: tenderness (61.2%), aching (60.7%), and firmness/tightness (59.8%). On multivariable analysis, cording was significantly correlated with functional difficulty for 17 actions. CONCLUSIONS: Patients frequently present with cording, potentially months after BC surgery. Risk factors for and symptoms of cording are identified, and treatment is recommended. Patients reporting cording are at higher risk of BCRL, therefore, cording should be incorporated into BCRL risk stratification.

Incidence and predictors of axillary web syndrome and its association with lymphedema in women following breast cancer treatment: a retrospective study.

PURPOSE: Axillary web syndrome (AWS) presents as a common postsurgical complication in individuals with breast cancer. Breast cancer-related lymphedema (BCRL) contributes to the shoulder and arm morbidity common in breast cancer survivors and often associated to cancer treatment. A paucity of literature exists evaluating the risk factors for developing AWS and the association between AWS and BCRL. The purposes of this study were (1) to identify risk factors for AWS in individuals with breast cancer, (2) to examine the association between BCRL and AWS, and (3) to determine if AWS increases the risk for developing BCRL. METHODS: A retrospective study of 354 women who underwent breast cancer treatment and received physical therapy was included. RESULTS: Axillary web syndrome developed in a third of women and predominately occurred in the first 8 postoperative weeks. The odds of AWS development were 73% greater for participants over the age of 60 (OR = 1.73, CI 95% 1.05-2.84). Women with AWS had 44% greater risk to develop lymphedema during the first postoperative year (RR = 1.44, CI 95% 1.12-1.84, p = 0.002). If AWS developed within the first postoperative month, women were almost 3 times more likely to develop lymphedema within the first 3 postoperative months compared with other women with AWS (RR = 2.75, CI 95% 1.199-6.310, p = 0.007). CONCLUSIONS: Our findings suggest that 30% of breast cancer survivors will have AWS during the first year of survivorship. As institutions prioritize screening efforts, early postoperative prospective surveillance is needed for women over 60 due to high risk for AWS development and any women with AWS for increased risk of lymphedema development based on our findings.

Correlation between superficial and deep lymphatic systems using magnetic resonance lymphangiography in breast cancer-related lymphedema: Clinical implications.

BACKGROUND: Magnetic resonance lymphangiography (MRL) has increased our knowledge of lymphatic anatomy and lymphedema pathophysiology and improved the efficacy of microsurgical procedures to manage peripheral lymphedema. The aim of this study is to investigate the ability of MRL to detect communications between superficial and deep lymphatic systems in breast cancer-related lymphedema (BRCL) and to investigate whether these communications could preserve lymphatic drainage of the hand. METHODS: Between 2008 and 2017 we used MRL imaging in 59 women with BCRL. Lymphedema of the arm and hand was detected in 30 patients while the hand was spared in 29. Using axial and coronal MRL reconstruction images we investigated the existence of any communication between the superficial and deep lymphatic systems. RESULTS: Among the 29 patients with spared hand, MRL revealed that 24 had at least one communicating lymphatic perforator at the wrist region (p < 0.001). Lymphatic flow at the axilla was clearly visualized in 16 of the 29 patients (55.2%), no perforating lymphatic vessels were detected in the group with lymphedema in the hand (30 patients). CONCLUSIONS: Communications between the deep and superficial lymphatic systems at the wrist region in BCRL patients without hand lymphedema should be considered when planning microsurgical lymphatic procedures at the wrist and in postoperative compression therapy.

Compression Vest Treatment for Symptomatic Breast Edema in Women Treated for Breast Cancer: A Pilot Study.

Background: Lymphedema of the breast/chest wall after breast cancer treatment is often associated with pain and reduced quality of life. We conducted a pilot study to evaluate whether the use of a compression vest reduced symptoms of breast/chest wall edema in breast cancer patients. Methods and Results: This single-center study included patients (n = 25) with symptomatic breast/chest wall edema with a pain score of ≥3 on the Numerical Rating Scales (range 1-10). The patients were instructed to wear a compression vest (Lymphatrex, Class II) for 6 months. Wilcoxon signed-rank tests were used to compare differences in patient-reported pain intensity/severity. Analyses included all patients with available data. In total, 17 (68%) continued to wear their vests for 6 months, whereas the other 8 withdrew prematurely. At baseline, median pain severity (4.9, interquartile range [IQR] 3.6-6.0) and pain interference (4.3, IQR 2.1-5.9) scores were significantly higher compared with pain scores after wearing the compression vest for 6 months (1.8 IQR 1.0-4.8 and 1.4 IQR 0.9-4.4, resp.). Patient-reported breast/chest wall swelling decreased from 92% (n = 22) at baseline to 71% (n = 12) at 6 months. The prevalence of moderate/severe patient-reported breast/chest wall pain declined from 63% (n = 15) at baseline to 18% (n = 3) at 6 months. Physical, emotional, and social functioning improved over time and was comparable to scores of the Dutch reference population. Conclusion: The results of this pilot study suggest that a compression vest could be an acceptable and effective treatment option for patients with painful breast/chest wall edema. In compliant patients, swelling and pain was significantly reduced.

The Concept of Chronic Edema-A Neglected Public Health Issue and an International Response: The LIMPRINT Study.

Lymphedema has always been a neglected global health care problem. A central requirement for the development of any chronic disease is the clear use of public health definitions that can be used internationally to define populations. The term "lymphedema" has historically been defined as either primary, resulting from failure of lymphatic development, or secondary, following damage to the lymphatics (e.g., cancer treatment, injury, or filariasis). Attempts to integrate causes of edema arising from damage to the venous system or the effects of gravity, immobility, and systemic disease have rarely been integrated. More recently, the prominent role of the lymphatics in tissue fluid homeostasis in all forms of chronic edema has been recognized. These advances led to the development of the term: "Chronic edema: a broad term used to describe edema, which has been present for more than three months." It can be considered an umbrella term that includes not only conventional "lymphedema" but also chronic swelling, which may have a more complex cause. This definition has been adapted in the international epidemiology study (LIMPRINT) that identified people throughout the health and social care systems in participating countries. Clearer definitions will allow for examination of this important public health problem that is likely to escalate given the projections of an aging population with multiple comorbidities. It will be possible to define both the hidden mortality and morbidity associated with complications, such as cellulitis and the impact on health-related quality of life. This evidence is urgently required to lobby for increased resource and effective health care in an increasingly competitive health care arena in which more established conditions have greater priority and funding.

The Development and Validation of the LIMPRINT Methodology.

The acronym Limprint stands for Lymphedema IMpact and PRevalence INTernational and was run under the auspices of the International Lymphedema Framework (ILF), a charity dedicated to improving provision of care globally. The primary aim was to identify the number of people with chronic edema (chronic edema present for >3 months and due to a range of underlying etiologies and associated risk factors) within diverse health services in nine participating countries and to determine its impact using validated methods. An international protocol and sampling framework, online data capture system, and standard operating procedures were adopted. An international consensus was used to create a core data tool that covered 13 domains. Specialist data on demographics and disability, details of swelling, wounds, cancer, and health-related quality of life were also available for sites. The study protocol was designed to allow flexibility in the types of studies undertaken within complex health care systems. All cases were confirmed using the modified pitting test. Sensitivity and specificity for this method were determined in Japanese and European populations. Following confirmation of a chronic edema case, Lymphologists defined whether it was a primary of a secondary form. The study was designed to provide robust evidence that chronic edema is an important and unrecognized public health problem in health services with significant morbidity. Without evidence of the size and complexity, it will remain considered a rare phenomenon and people affected will be denied access to appropriate treatment that would allow them to have fulfilled and productive lives.

Prevalência de linfedema após mastectomia em portadoras de câncer de mama: uma revisão sistemática acerca da influência da reconstrução imediata / Prevalence of lymphedema after mastectomy in women living with breast cancer: a systematic review of the influence of immediate reconstruction

Este estudo objetivou analisar, por meio de uma revisão sistemática da literatura, a influência da reconstrução imediata na prevalência de linfedema após mastectomia em pacientes portadoras de câncer de mama. Foram analisados os mais relevantes estudos publicados originalmente em qualquer idioma até agosto de 2018, indexados às bases de dados US National Library of Medicine, Cochrane Central Register of Controlled Trials, Web of Science e Scientific Electronic Library Online. A amostra foi composta por 10 publicações que se adequaram aos critérios de inclusão e exclusão estabelecidos, incluindo 2.425 pacientes submetidas a apenas mastectomia e 2.772 pacientes submetidas à mastectomia associada à reconstrução imediata da mama. A prevalência de linfedema foi 20,95% nas pacientes submetidas a apenas mastectomia (n = 508) e de 5,23% nas pacientes submetidas à mastectomia associada à reconstrução imediata (n = 145), havendo diferença estatisticamente significativa (p < 0,001). Concluiu-se que a mastectomia associada à reconstrução imediata influencia positivamente o prognóstico das pacientes portadoras de câncer de mama, proporcionando um índice significativamente menor de linfedema, quando comparada à realização de apenas mastectomia.

This study aimed to analyze, through systematic review of literature, the influence of immediate reconstruction on the prevalence of lymphedema after mastectomy, in women living with breast cancer. The analysis considered the most relevant studies originally published, in any language, up to August 2018, indexed on the databases of the US National Library of Medicine, Cochrane Central Register of Controlled Trials, Web of Science, and Scientific Electronic Library Online. The sample comprised 10 publications that met the established criteria for inclusion and exclusion, including 2,425 patients who were subjected to mastectomy alone, and 2,772 patients who were subjected to mastectomy associated with immediate reconstruction of the breast. The prevalence of lymphedema was 20.95% in patients who had been subjected to mastectomy alone (n = 508), and 5.23% among those patients who were subjected to mastectomy associated with immediate reconstruction of the breast (n = 145), the difference being statistically significant (p < 0.001). We concluded that mastectomy, when associated with immediate breast reconstruction, has a positive influence on the prognosis of patients living with breast cancer, thereby providing a much lower rate of lymphedema when compared with mastectomy alone.

Complex Decongestive Therapy in Breast Cancer-Related Lymphedema: Does Obesity Affect the Outcome Negatively?

BACKGROUND: The aim of this prospective clinical study was to compare the long-term efficacy of complex decongestive therapy (CDT) in obese and nonobese patients with breast cancer-related lymphedema (BCRL). MATERIALS AND METHODS: A total of 59 patients (29 obese patients group 1, 30 normoweight overweight patients group 2) with unilateral BCRL were enrolled. All patients underwent CDT that included manual lymphatic drainage, intermittent pneumatic compression pump, multilayer compression bandaging, lymphedema exercises, and skin care. The CDT was performed for 1 hour a day, 5 days a week for 3 weeks. Patients were assessed according to limb volume difference before CDT, after CDT, and after 1 year. RESULTS: The initial lymphedema volume of group 1 was 866.34 ± 389.34 mL and that of group 2 was 661.84 ± 470.6 mL (p = 0.031). The lymphedema severity percentage of excess volume (PEV) of group 1 was 33.37 ± 15.71 and that of group 2 was 31.86 ± 19.63, which was moderate lymphedema. After 15 sessions of CDT program, in group 1, lymphedema volume decreased to 771.46 ± 389.14 mL (post-CDT p = 0.013) and in group 2, lymphedema volume decreased to 468.38 ± 417.36 mL (post-CDT p < 0.0001), and in group 1, PEV decreased to 28.54 ± 16.84 (post-CDT p = 0.002) and that in group 2 decreased to 22.1 ± 16.87 (post-CDT p < 0.0001). After 1 year, group 1 reached the baseline values of the extremity volumes, but in group 2, the volumes of extremities could maintain their post-CDT values. CONCLUSION: Obesity is a factor that deteriorates the CDT efficacy. Early treatment, before developing fat accumulation and fibrosis, must be primary goal in the treatment of BCRL.

Do Compression Sleeves Reduce the Incidence of Arm Lymphedema and Improve Quality of Life? Two-Year Results from a Prospective Randomized Trial in Breast Cancer Survivors.

BACKGROUND: In a previous randomized controlled trial it has been demonstrated that arm compression sleeves worn immediately after breast cancer surgery, including axillary lymph node removal in addition to physical therapy are able to reduce the occurrence of early postoperative swelling and of arm lymphedema up to 1 year and to improve quality of life. The aim of the present investigation was to check the further development of the arm swelling in patients using compression sleeves or not, and to compare the quality of life in women treated due to breast cancer 2 years after surgery. MATERIALS AND METHODS: Twenty from originally 23 patients who still wore their compression sleeves (15 mmHg) and 21 from 22 patients who had been randomized into the control group without compression could be seen after one more year. Arm volume measurements were performed and quality of life (QLQ-C30 and QLQ-BR23 questionnaires) was assessed. RESULTS: Three from 20 patients in the compression group (CG) and 6 from 21 without compression showed arm lymphedema, defined by an increase of the arm volume exceeding 10% compared with the preoperative values. Significant improvement of several quality of life parameters were found in the CG. CONCLUSION: Light compression sleeves worn for 2 years are not only able to reduce the incidence of early postoperative edema and of lymphedema, but also lead to a significant improvement of important quality-of-life parameters like physical functioning, fatigue, pain, arm and breast symptoms, and future perspectives.

Bone loss in the affected forearm in patients with breast cancer-related lymphedema: a controlled study.

PURPOSE: We aimed to investigate the association between lymphedema and bone mass density (BMD) of affected and unaffected forearms in patients with breast cancer-related lymphedema (BCRL). We also explored whether there was a relationship between any disability and BMD on the affected side. METHODS: We evaluated 111 patients (53.75 ± 9.07) with unilateral lymphedema (group 1) and 61 patients (50.90 ± 12.44) without lymphedema (group 2) after breast cancer surgery. BMD was performed by dual-energy x-ray absorptiometry (DXA) in lumbar spine, femoral neck, and distal forearm on both sides. Functional situation was assessed by the Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire. RESULTS: The total Z score (p = 0.018), T score (p = 0.005), and BMD value (p = 0.014) were lower in the affected forearm than the unaffected forearm in group 1. There was no difference between the affected or unaffected sides in the total Z score (p = 0.394), T score (p = 0.518), and BMD value (p = 0.629) in group 2. The DXA measurements in terms of the total forearm Z, T scores, and BMD value on the affected side were statistically significantly different between the groups. There was no difference between groups in the femur neck and lumbar total Z and T scores. There was also a positive correlation between the QuickDASH scores and lymphedema stage (r = 0.469, p = 0.001) and the duration without treatment of lymphedema (r = 0.298, p = 0.02) in group 1. CONCLUSION: We recommend early diagnosis and treatment of lymphedema for the protection of upper extremity disability and localized osteoporosis in patients with BCRL.

Validity and Reliability of Three-Dimensional Imaging for Measuring Breast Cancer-Related Lymphedema in the Upper Limb: A Cross-Sectional Study.

Background: In the past, measurement of upper limb lymphedema was done by water displacement (WD), which is frequently cited as the gold standard. For various reasons, however, the use of WD is restricted in clinical settings. A more precise and easy-to-use method would be favorable. The high precision of three-dimensional (3D) imaging in comparison to WD has already been reported for healthy subjects. The aim of this study is to determine the validity and reliability of 3D imaging by comparing it to the WD method in women with unilateral upper limb lymphedema. Methods and Results: Thirty-nine women with unilateral breast cancer-related lymphedema (BCRL) were included, of which 37 completed two volume measurement techniques (3D and WD) on the BCRL and contralateral healthy arm. Slightly larger volumes were measured by the WD method in healthy arms (+9.8 mL; p = 0.058) and also in BCRL arms (+18.5 mL; p < 0.001). All measurements were performed twice by the same researcher to evaluate reliability. There was no significant difference between the two measurements for healthy arms (p = 0.323) or BCRL arms (p = 0.807) in 3D imaging. Bland-Altman plots showed a high limit of agreement between the single measurements. 3D imaging had a high intrarater reliability (Intraclass Correlation Coefficient = 0.999). Conclusion: Results show that 3D imaging is an innovative method for measuring upper limb volume in BCRL patients. Even though image processing is time consuming, 3D imaging combines high reproducibility with high precision. By software automation, this technique could easily be integrated into clinical routine. It is for this reason that we would recommend implementing the Vectra 3D imaging technique for measurement of BCRL.

Lymphovascular invasion and extranodal tumour extension are risk indicators of breast cancer related lymphoedema: an observational retrospective study with long-term follow-up.

BACKGROUND: Breast cancer related lymphoedema (BCRL) occurs in a substantial proportion of breast cancer survivors and is a major contributor to patients' disability. Regrettably, there are no validated predictive biomarkers, diagnostic tools, and strong evidence-supported therapeutic strategies for BCRL. Here, we provide an integrative characterization of a large series of women with node-positive breast cancers and identify new bona fide predictors of BCRL occurrence. METHODS: Three hundred thirty-two cases of surgically-treated node-positive breast cancers were retrospectively collected (2-10.2 years of follow-up). Among them, 62 patients developed BCRL. To identify demographic and clinicopathologic features related to BCRL, Fisher's exact test or Chi-squared test were carried out for categorical variables; the Wilcoxon rank-sum was employed for continuous variables. Factors associated with BCRL occurrence were assessed using a Cox proportional hazards regression model. RESULTS: En-bloc dissection of the axillary lymph nodes but not the type of breast surgery impacted on BCRL development. Most of BCRL patients had a Luminal A-like neoplasm. The median number of lymph nodes involved by metastatic deposits was significantly higher in BCRL compared to the control group (p = 0.04). Both peritumoral lymphovascular invasion (LVI) and extranodal extension (ENE) of the metastasis had a negative impact on BCRL-free survival (p = 0.01). Specifically, patients with LVI and left side localization harboured 4-fold higher risk of developing BCRL, while right axillary nodes metastases with ENE increased the probability of BCRL compared to ENE-negative patients. CONCLUSIONS: Assessment of LVI and ENE should be integrated with clinical and surgical data to improve BCRL risk stratification.

Correlation of Bioimpedance Spectroscopy with Risk Factors for the Development of Breast Cancer-Related Lymphedema.

Background: We reviewed serial bioimpedance measurements in order to quantify the relationship between changes in these scores and a patient's risk for developing breast cancer-related lymphedema (BCRL). Methods and Results: From April 2010 through November 2016, 505 patients were prospectively evaluated using bioimpedance spectroscopy (BIS/L-Dex). Patients received preoperative and postoperative L-Dex measurements and were categorized based upon risk for BCRL with respect to axillary staging procedure, radiation use, taxane use, and body mass index (BMI). L-Dex change was associated with the type and number of BCRL risk factors. Both axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) were associated with a greater change in L-Dex (p < 0.001), although elevated BMI was not associated. The median, maximal change in L-Dex for patients treated with ALND, RNI, and taxanes was 16.7 versus 5.2 for ALND alone and 3.7 for sentinel lymph node biopsy (SLNB) alone (p = 0.016). In a model using all four risk factors to predict the maximal change in L-Dex, ALND and RNI remained significantly associated with maximum change (p < 0.05). The time required to reach maximal change in L-Dex was shorter in patients treated with ALND or RNI (the time for 25% of patients achieving an L-Dex ≥7 was 4.3 months for ALND, RNI, and taxanes patients versus 30.8 months for SLNB-alone patients). Conclusions: Risk factors for development of BCRL were associated with both the magnitude and timing of change in L-Dex scores. These findings demonstrate the utility of serial L-Dex measurements in providing an objective assessment of a patient's lymphedema status and the value of L-Dex serial measurements to assist in monitoring patients for the development of BCRL. This supports the clinical utilization of serial L-Dex scores to follow patients at risk for BCRL.