New insights in breast cancer-related lymphedema.

Upper limb lymphedema after breast cancer treatment including axillary dissection occurs in almost 20% of women. Its treatment consists of complete decongestive physiotherapy based on low-stretch bandage to reduce volume, followed by elastic compression to maintain it. In this article, we will detail recent data on lymphedema risk factors with possible genetic predisposition, prevention (surgical, compression), manual lymphatic drainage, physical activity, weight, advice, and treatments including gene therapy.

Breast cancer-related lymphedema: A critical review on recent progress.

Lymphedema is a chronic and debilitating condition characterized by an abnormal buildup of protein-rich fluid in the interstitial tissue, leading to the development of edema and tissue structural alterations. Breast cancer-related lymphedema (BCRL) remains a significant healthcare burden because it can develop within days and up to 11-years after the surgery. Specifically, axillary lymph node dissection leads to 30-50 % upper limb lymphedema, which involves the accumulation of protein-rich fluid. In this article, we provide a comprehensive/critical overview of post-mastectomy lymphedema, focusing on key aspects as diagnosis, prevention, and treatment methods. Beginning with clinical condition, the article explores the pathophysiology and risk factors associated with post-mastectomy lymphedema. It further delves into various diagnostic modalities available, highlighting the importance of early detection for optimal management of BCRL. We also examine preventive strategies, emphasizing the role of patient education, lifestyle modifications, and proactive measures in reducing the risk of lymphedema development. In terms of treatment, the article covers a wide array of interventions ranging from conservative approaches like manual lymphatic drainage and compression therapy to surgical techniques such as lymph node transfer and lymphaticovenular anastomosis. Thus, through a comprehensive synthesis of current evidence and clinical practices updates, the review aims to guide healthcare professionals in delivering preventive and effective care while improving outcomes for individuals affected by post-mastectomy lymphedema.

Evidence for the clinical effectiveness of decongestive lymphoedema treatment for breast cancer-related arm lymphoedema, a systematic review.

PURPOSE: Early treatment is advised for breast cancer-related arm lymphoedema (BCRL), a common sequelae of breast cancer treatment. Expert guidance recommends two-phase decongestive lymphoedema treatment (DLT), although evidence is lacking for current treatment protocols and UK women are routinely offered self-treatment with hosiery. This systematic review considered evidence regarding treatment of early BCRL, that is, within 12 months of developing BCRL. METHODS: A systematic review of evidence for clinical effectiveness of DLT for women with less than 12-month BCRL duration (early BCRL) was undertaken using the Joanna Briggs Institute (JBI) method. Studies included women with < 12-month or mean < 9-month BCRL duration; some studies reported only one eligible group. The original search was conducted in 2016 and updated in 2018 and 2022. Methodological quality of identified studies was assessed using JBI critical appraisal instruments. Outcomes of interest were extracted with eligible results displayed in narrative and tabular format. Strength of evidence was rated using the GRADE system. RESULTS: Seven trials and three descriptive studies provided weak evidence (grade B) for effectiveness of DLT for early BCRL. Heterogeneous protocols limited comparison of findings. There was no evidence for the most effective treatment or treatment combination or optimal frequency or duration of treatment. CONCLUSION: There is no evidence to justify change in current lymphoedema treatment, whether self-treatment with hosiery (UK) or two-phase DLT (other countries). Further research for the early BCRL population is required. IMPLICATIONS FOR CANCER SURVIVORS: Women with early BCRL require early and effective treatment although this updated review shows there is still no evidence for what that treatment should be.

LYMPH-Q translation, cultural adaptation and validation in Italian language: A prospective PROMs-based study on breast cancer-related arm lymphedema for patients' education.

BACKGROUND: Upper Extremity Lymphedema following oncological breast surgery affects not only the patient's physique, but also the patient's psychological sphere. One of the best known PROMs-based questionnaires for investigating the condition is the LYMPH-Q. The study aimed to perform the Italian translation and cultural adaptation of the LYMPH-Q and to assess if, independently from disease evolution, arm sleeve improves QoL in these patients. MATERIALS AND METHODS: Translation included 4 steps: Forward translation, Back translation, Back translation review and Patient interviews. The questionnaire was administered to 50 female patients older than 18 years of age with UEL who received a prescription for daily use of a compression sheath. A second administration took place 30 days after. Forty-four patients completed the study (Group 1: 26 patients with indication to use compression sleeve who wore it; Group 2:18 patients who despite the prescription did not want to wear it. A descriptive statistical analysis was performed with Prism 9 software. RESULTS: T-tests showed statistical significance for changes in "Symptoms," "Function," "Appearance" and "Psychological" scales. There were no statistically significant changes for "Information scale" in Group 1 and for all scales in Group 2. CONCLUSION: Data from this observational study show that HR-QOL analyzed from the patients' perspective also tends to improve in terms of symptoms, function, appearance, and psychological sphere in patients with BCRL when using a compression sheath. The Lymph-Q has proven to be a valuable ally of the physician attempting to improve treatment approaches for BCRL based not only on scientific evidence but also on PROMs.

Analysis of Different Lymphedema Assessment Tools in Women with Breast Cancer After Mastectomy.

Background: Lymphedema is a common complication after mastectomy in women with breast cancer. Several methods have been described to assess and diagnose lymphedema, one of the most studied being the perimeter and ultrasonography. However, the reliability of these methods and the correlation between them are still controversial. The aim of this study was to analyze the reliability of cytometry and ultrasound imaging in the assessment of lymphedema after mastectomy in women with breast cancer and to study the correlation between them. Methods and Results: A cross-sectional study was conducted in 29 women with mastectomy after breast cancer. Lymphedema in the arm was measured both with cytometry and ultrasonography. Reliability was calculated with intraclass correlation coefficient. The correlation between the two methods was carried out with the Pearson correlation coefficient. Both cytometry (M1: α = 0.999, ICC = 0.996; M2: = α = 0.998, ICC = 0.994) and ultrasonography (M1: α = 0.992, ICC = 0.976; M2: = α = 0.991, ICC = 0.973) are reliable methods to assess lymphedema in the arm. No significant correlation was found between them (p > 0.05). Conclusions: Cytometry and ultrasonography appear to be adequate for the measurement of edema in women with breast cancer after mastectomy. However, for an accurate measurement of lymphedema, these measurements should not be used interchangeably.

Prevention and Treatment of Lymphedema in Breast Cancer.

Breast cancer related lymphedema (BCRL) affects many breast cancer survivors and drastically affects their quality of life. There are several surveillance methods for BCRL that are critical at early detection. Prevention of BCRL involves knowledge of alternatives to aggressive axillary surgery, avoidance of axillary surgery, and de-escalation of axillary surgery. There are also techniques to better delineate the anatomy in the axilla to avoid taking nodes that drain the upper extremity. A multidisciplinary approach with medical oncology and radiation oncology can also help avoid unnecessary surgery or radiation that can together strongly increase the risk of BCRL.

Contemporaneous Symptom Networks of Breast Cancer-Related Upper Limb Lymphedema: A Network Analysis.

BACKGROUND: Upper limb lymphedema (ULL) is a common and deliberating complication for breast cancer survivors (BCSs). Breast cancer survivors with ULL reported a wide range of symptoms. However, little is known about symptom patterns and interrelationships among them. This study was designed to explore symptom clusters and construct symptom networks of ULL-related symptoms among BCSs and to identify the core symptoms. METHODS: This study is a secondary data analysis using datasets from three cross-sectional studies of BCSs in China. A total of 341 participants with maximum interlimb circumference ≥2 cm and complete responses in Part I of the Breast Cancer and Lymphedema Symptom Experience Index were included. Symptom clusters were identified through principal component analysis, and multiple linear regression analysis was employed to explore factors associated with severity of overall ULL-related symptoms. A contemporaneous network with 20 frequently reported symptoms were constructed after controlling for covariates. RESULTS: Three symptom clusters, including lymph stasis symptom cluster, nerve symptom cluster, and movement limitation symptom cluster, were identified. Postsurgery time, axillary lymph node dissection, and radiotherapy were associated with the severity of ULL-related symptoms. Tightness (rs = 1.379; rscov = 1.097), tingling (rs = 1.264; rscov = 0.925), and firmness (rs = 1.170; rscov = 0.923) were the most central symptoms in both networks with and without covariates. CONCLUSIONS: Breast cancer survivors with ULL experienced severe symptom burden. Tightness, tingling, and firmness were core symptoms of ULL among BCSs. Our findings demonstrated that the assessment and targeted intervention of specific core symptoms might help to relive effectively the burden of ULL-related symptom among BCSs.

A comparative evaluation of the efficacy of complete decongestive therapy in the treatment of unilateral breast cancer-related lymphedema with and without metabolic syndrome.

AIM: This study aimed to investigate the effect of the presence of metabolic syndrome (MetS) on the limb volume and quality of life (QoL) of patients who underwent complex decongestive therapy (CDT) due to unilateral breast cancer-related lymphedema (BCRL). METHODS: Forty female patients with unilateral BCRL, of whom 20 had MetS (MetS group) and 20 did not have MetS (control group), were included in the study. The participants received CDT 5 days a week for 3 weeks. The participants' limb volume (percentage of excess volume (PEV) and percentage reduction of excess volume (PREV) was determined using a tape measure, and their QoL was assessed using the Lymphedema Quality of Life questionnaire (LYMQoL) before and after treatment. RESULTS: After the treatment, the PEV and PREV values and LYMQoL-symptoms scores of the patients improved (p < 0.05); however, the LYMQoL-function, appearance/body image, mood/emotions, and overall QoL scores did not change in the MetS group (p > 0.05). In the control group, the PEV and PREV values and the LYMQoL-appearance/body image, mood/emotions, and overall QoL scores improved (p < 0.05), but the LYMQoL-symptoms and LYMQoL-function scores did not change (p > 0.05). There was a greater increase in the post-treatment PEV and PREV values of the control group compared to the MetS group (p < 0.001). CONCLUSION: The study yielded that CDT was an effective treatment in BCRL with and without MetS; however, the improvement was greater in BCRL cases without MetS than in those with MetS. Therefore, the presence of MetS should be taken into account in the treatment of lymphedema in patients who develop BCRL. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT05426993. Registered 2022-06-16. https://clinicaltrials.gov/search?cond=NCT05426993.

Development and validation of a nomogram for breast cancer-related lymphedema.

To establish and validate a predictive model for breast cancer-related lymphedema (BCRL) among Chinese patients to facilitate individualized risk assessment. We retrospectively analyzed data from breast cancer patients treated at a major single-center breast hospital in China. From 2020 to 2022, we identified risk factors for BCRL through logistic regression and developed and validated a nomogram using R software (version 4.1.2). Model validation was achieved through the application of receiver operating characteristic curve (ROC), a calibration plot, and decision curve analysis (DCA), with further evaluated by internal validation. Among 1485 patients analyzed, 360 developed lymphedema (24.2%). The nomogram incorporated body mass index, operative time, lymph node count, axillary dissection level, surgical site infection, and radiotherapy as predictors. The AUCs for training (N = 1038) and validation (N = 447) cohorts were 0.779 and 0.724, respectively, indicating good discriminative ability. Calibration and decision curve analysis confirmed the model's clinical utility. Our nomogram provides an accurate tool for predicting BCRL risk, with potential to enhance personalized management in breast cancer survivors. Further prospective validation across multiple centers is warranted.

The effect of exercise and educational programs for breast cancer patients on the development of breast cancer-related lymphoedema: secondary endpoint from a randomized controlled trial in the Setouchi Breast Project-10.

BACKGROUND: Although the association between higher physical activity and preventive effect on breast-cancer-related lymphoedema (BCRL) has been reported, it is unclear what intervention is optimal. We aimed to investigate the effect of exercise and educational programs on BCRL development. METHODS: This study was a secondary endpoint analysis from a prospective randomized controlled trial. We enrolled patients with stage 0-III breast cancer from March 2016 to March 2020 and randomly assigned them to the control (n = 111), education (n = 115), or exercise (n = 104) group. As secondary endpoint, we assessed the incidence of and preventive effect on BCRL at 12 months post-intervention. RESULTS: There were no significant differences in the incidence of BCRL at 12 months post-intervention between the exercise and control groups (9.8% and 10.8%, P = 0.83) and the education and control groups (11.6% and 10.8%, P = 1.00). There were no significant differences in time to BCRL onset from the day of surgery between the exercise and control groups (event rate at 12 months: 20.7% and 17.2%, log-rank, P = 0.54) and the education and control groups (18.8% and 17.2%, log-rank, P = 0.57). The multivariable analyses indicated that axillary dissection and obesity significantly increased the risk of BCRL [hazard ratio (HR): 2.36, 95% confidence interval (CI) 1.52-3.67 and HR: 1.68, 95% CI 1.07-2.63, respectively]. CONCLUSIONS: The intervention did not decrease the risk of BCRL, and axillary dissection and obesity were the risk factors of BCRL. TRIAL REGISTRATION NUMBER: UMIN000020595 at UMIN Clinical Trial Registry.

Complex decongestive therapy improves finger tapping score in patients with breast cancer-related lymphedema.

PURPOSE: Breast cancer-related lymphedema (BCRL) impairs upper limb function and cognitive performance. This study aimed to evaluate the effects of fifteen sessions of complex decongestive therapy (CDT) on fine motor performance and information processing speed in women with BCRL. METHODS: Thirty-eight women with BCRL (54.97 ± 10.78 years) were recruited in the study. Participants either received five times weekly CDT consisting of manual lymphatic drainage, skin care, compression bandaging, and remedial exercises (n = 19) or served as a wait-list control group (n = 19). We used the Finger Tapping Task to assess fine motor performance and the Digit Symbol Substitution Test to assess information processing speed. ANCOVA was performed to analyze the effect of CDT on the dependent variables, adjusting for covariates and baseline values. RESULTS: CDT significantly improved finger tapping score (p < 0.001) compared to the wait-list to the control group, whereas information processing speed did not significantly change (p = 0.673). CONCLUSION: The findings suggest that CDT is an effective conservative therapeutic approach to improve upper extremity fine motor function in women with BCRL. Future studies are needed to investigate the effect of CDT on different cognitive domains.

Influence of the anchor system on body sway in women affected and not affected by lymphedema secondary to breast cancer: A cross-sectional study.

BACKGROUND: Postural control is an essential ability for functional independence modified by therapeutic approaches and morbidities secondary to breast cancer. The anchor system enables additional haptic perception of body position in front of the support base and can be used alone or in conjunction with sensorimotor training. RESEARCH QUESTION: What is the influence of the anchor system, through different manual contacts on the upper limb, on body sway in women affected and not affected by lymphedema secondary to breast cancer treatment? METHODS: Cross-sectional study involving 60 women homogeneously distributed to the group affected by lymphedema (GAL), with a mean age of 62.53 (SD = 12.54) years and upper limb volume difference (ULVD = Ipsilateral - Contralateral) of 636.21 (SD = 387.94) cm3, and group not affected by lymphedema (GNAL), with a mean age of 57.24 (SD = 11.43) years and ULVD of -8.91 (SD = 121.72) cm3. Baropodometry was used to assess body sway, through the presence and absence of the visual sense, associated with different manual contacts of the anchor system designated absence, simulation of use, unilateral and bilateral contact. The Shapiro-Wilk and Student's T-tests with Bonferroni Post-Hoc were used in the statistical analysis (p ≤ 0.05). RESULTS: The GAL expressed non-significant values compared to the GNAL in the absence of visual sense and non-use of the anchor system. The unilateral contact of the anchor system on the preferred upper limb in the presence of the visual sense, and bilateral contact of the anchor system in the presence and absence of the visual sense promoted a significant reduction of body sway in both groups. SIGNIFICANCE: In breast cancer survivors, the anchor system with bilateral contact effectively maintains postural control, regardless of the visual sense and the volume of the upper limb.

The role of breast cancer-related arm lymphedema in physical functioning and physical activity participation among long-term African American breast cancer survivors.

PURPOSE: Breast cancer-related arm lymphedema (BCRL) is a common chronic and debilitating condition that involves accumulation of lymphatic fluid in the arm or hand. Limited data are available on BCRL in African American women. Lack of physical activity (PA) and poor physical functioning (PF) are both associated with increased morbidity and mortality among breast cancer survivors. We examined the association of BCRL with PA and PF among African American breast cancer survivors. METHODS: 323 African American women who previously participated in a case-only study in three states (TN, GA, SC) completed a survivorship-focused questionnaire (mean: 4.2 years post-diagnosis) in 2015-2016. Validated measures were used to determine BCRL, PF, and PA. Adjusted binary logistic regression models estimated ORs and 95% CIs for the association of BCRL and meeting PA guidelines (≥ 150 min/week), while multinomial logistic regression was used for PF and PA (minutes/week) categorized based on tertiles. RESULTS: Approximately 32% reported BCRL since diagnosis; 25.4% reported BCRL in the last 12-months. About 26% and 50% reported that BCRL interfered with exercise and ability to do daily activities, respectively. The mean PF among those with BCRL was 51.0(SD:29.0) vs. 68.5(SD:30.1) among those without BCRL. BCRL was associated with lower PF (adjusted-OR for tertile 2: 2.12(95% CI:1.03-4.36) and adjusted-OR for tertile 1: 2.93(95% CI:1.44-5.96)). CONCLUSIONS: BCRL was associated with lower PF among long-term African American breast cancer survivors. Continued monitoring by health care professionals and increased education and behavioral interventions to support PA and improved PF among survivors living with BCRL are warranted.

The Impact of Obesity on Success of Immediate Lymphatic Reconstruction for Prevention of Breast Cancer-Related Lymphedema.

BACKGROUND: Breast cancer-related lymphedema (BRCL) is a potential sequela of high-risk breast cancer treatment. Preventive treatment with immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) has emerged as the standard of care; however, there is relatively little known about factors that may contribute to procedural failure. METHODS: A retrospectively maintained, institutional review board-approved study followed patients who underwent ILR at the time of ALND at our tertiary care center between May 2018 and May 2023. Patients who presented for at least one follow-up visit in our multidisciplinary lymphedema clinic met the criteria for inclusion. Patients who developed lymphedema despite ILR and potential contributing factors were further explored. RESULTS: 349 patients underwent ILR at our institution between May 2018 and May 2023. 341 of these patients have presented for follow-up in our multidisciplinary lymphedema clinic. 32 (9.4%) patients developed lymphedema despite ILR. This cohort was significantly more likely to be obese (56% vs 35%, P = 0.04). Multivariate logistic regression demonstrates increased odds of procedural failure in patients with a body mass index (BMI) ≥30 kg/m2 (odds ratio 2.6 [1.2-5.5], P = 0.01). CONCLUSION: These data comment upon our institutions outcomes following ILR. Patients who develop lymphedema despite ILR tend to have a higher BMI, with a significantly increased risk in patients with a BMI of 30 or greater. Consideration of these data is critical for preprocedural counseling and may support a BMI cutoff when considering candidacy for ILR going forward, as well as when optimizing failures for secondary lymphedema procedures.

Defining breast cancer-related lymphedema (BCRL) prevalence and risk factors: A pragmatic approach to lymphedema surveillance.

Introduction: We presented the key findings from Singapore's Changi General Hospital Breast Centre's lymphedema surveillance strategy that used patients' reported symptoms, standard arm circumference measurements and clinical assessment in the diagnosis of breast cancer-related lymphedema (BCRL). Our secondary aim was to highlight and discuss important elements of a surveillance strategy that can be implemented to track this outcome measure of breast cancer treatment for future research. Method: We conducted a cross-sectional study of 511 breast cancer patients to assess the prevalence of BCRL and its associated risk factors. We defined BCRL prevalence rates based on patients' self-reporting, objective arm circumference measure-ments and clinical diagnosis based on International Society of Lymphology (ISL) staging. Results: The median follow-up of patients was 88.8 months. The cumulative prevalence rate in the cohort was 30.9%. The cohort of BCRL patients were older (58.4 versus [vs] 54.9 years), had higher mean Body Mass Index (27.7 vs 25.2), higher proportion of mastectomy (77% vs 64.3%), axillary clearance, less likely breast reconstruction, higher-grade tumour, more lymph nodes excised, more advanced nodal disease, and had undergone adjuvant chemotherapy. However, clinically apparent BCRL was only 6.5% (33 out of 511 patients). The proportion of clinically significant BCRL in patients undergoing sentinel lymph node biopsy (SLNB) or axillary sampling was 1.7% compared to 9.9% in patients who had undergone axillary clearance. Majority of the BCRL were subclinical or mild in severity. Conclusion: Our study showed that our rates of BCRL were comparable to international rates and highlighted similar patient profiles who were at risk of developing the disease. Having a comprehensive lymphedema surveillance strategy is paramount in paving the way for future studies.

Axillary Reverse Mapping Aids in Reducing the Rates of Breast Cancer-Related Lymphedema in Underserved Ethnically Diverse Population.

BACKGROUND: Breast cancer-related lymphedema (BCRL) poses a significant risk following sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND), particularly affecting ethnic minorities, with a twofold increased risk. Axillary reverse mapping (ARM), a novel technique, shows potential in reducing BCRL rates, yet its utility in ethnic minorities lacks sufficient exploration. Therefore, our study aims to investigate the utility and outcomes of ARM on BCRL in an ethnic diverse group. METHODS: A retrospective chart review of ARM patients from January 2019 to July 2022 was conducted, monitoring patients over 24 months at 3-month intervals using SOZO® scores, with comparisons with preoperative baselines. RESULTS: Of the 212 patients, 83% belonged to ethnic minorities. SLNB was performed in 83%, ALND in 17%, and 62.3% underwent radiation therapy. Positive lymph nodes were found in 31.6%, with 22.2% exhibiting blue nodes and 25.9% exhibiting blue lymphatics. Of identified blue nodes, 70.2% were excised, including 51.5% crossover nodes. Lymphedema occurred in 3 patients, resulting in a BCRL rate of 1.4%. Compared with an historical BCRL incidence of 40.4% following ALND in ethnic minorities, our study reported a significantly lower rate of 8% (p < 0.001). CONCLUSION: The ARM procedure can significantly lower BCRL in ethnic minority groups. The combination of ARM and bioimpedance spectroscopy led to a remarkably low BCRL rate of 1.4%. Notably, none of the patients in our study developed an axillary recurrence at 24-month follow-up. Nevertheless, future studies with larger sample sizes are warranted to better understand the utility of the ARM technique in this population.