The Effectiveness of Prophylactic Compression Sleeves in Reducing the Risk of Lymphedema in Patients Who Receive Breast Cancer Surgery: A Systematic Review.

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. 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. 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. 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.

Background Chronic inflammatory responses initiated by lymphatic injury play a key role in the pathophysiology of secondary lymphedema. However, it is unclear if baseline inflammation or ethnic/racial variability in inflammatory responses increase lymphedema risk. Crown-like structures of the breast (CLS-B), consisting of macrophages engulfing necrotic adipocytes, are a marker of systemic inflammation and have been implicated in the pathogenesis of breast cancer, but their role in lymphedema development is unknown. Here we determine whether baseline differences in inflammation, characterized by the presence of CLS-B, contributed to lymphedema risk in a diverse cohort of patients treated with ALND. Methods Patients ≥ 18 years undergoing ALND were enrolled in a prospective lymphedema screening study. Body mass index (BMI) and volumetric arm measurements (perometer) were performed at baseline, postoperatively, and every 6 months. Breast tissue obtained at definitive surgery was assessed for CLS-B with CD-68 IHC stain in non-tumor breast tissue. Inflammation severity was determined by number of CLS-B/cm2, with the median used to differentiate between mild and severe inflammation. Lymphedema was defined as a relative arm volume change of ≥10%. Lymphedema incidence was assessed using competing risk analysis and compared between patients with and without CLS-B. Uni- and multivariable analysis was performed to identify factors associated with lymphedema development. Results Between 11/2016-03/2020, 304 ALND patients were enrolled; 281 had at least 6 months of follow-up and were included in the study. Eleven percent self-identified as Asian, 20% Black, 6% Hispanic, and 60% White. Median age was 48 years; median BMI was 26.3 kg/m2, with higher BMI observed in Black and Hispanic women compared to Asian and White women (p < 0.001). Overall, 54% had CLS-B, with severe inflammation (> 0.4 CLS-B/cm2) identified in 71 (25%) patients. CLS-B presence correlated with BMI (36% [BMI < 25], 63% [BMI 25-30], 70% [BMI > 30], p < 0.001) and varied across racial/ethnic groups, with a higher prevalence in Black and Hispanic women (68% [Black], 69% [Hispanic] vs 59% [Asian], 46% [White], p = 0.03) (Table). Inflammation severity did not differ by race/ethnicity (p = 0.11). At 2.1 years median follow-up (IQR 1.6-3.1), 66 women developed lymphedema, with a 2-year lymphedema rate of 21.3% (95% CI 16.4-26.8). Lymphedema incidence was higher among Black and Hispanic women, compared to Asian and White women (2-year rate: 33.8% [Black], 31% [Hispanic], 17.4% [Asian], 18.2% [White], p = 0.002), and was higher among women with CLS-B (2-year rate: 28.2% [CLS-B] vs 12.9% [no CLS-B], p = 0.02). On multivariable analysis, Black race (White [referent]: HR 2.85, 95% CI 1.4-5.8; p = 0.03), receipt of NAC (upfront surgery [referent]: HR 2.46, 95% CI 1.04-5.8, p = 0.04) and older age (HR 1.03, 95% CI 1.01-1.06 per 1-year increase; p = 0.009) were independently associated with lymphedema development, while CLS-B was not (HR 1.37, 95% CI 0.81-2.34, p = 0.2). Conclusions In a prospective cohort of patients treated with ALND, Black race, receipt of NAC, and increasing age, but not CLS-B, were independently associated with lymphedema risk. However, the higher CLS-B prevalence in Black women suggests that they may have a propensity for increased inflammation, which may in part be contributing to the higher lymphedema risk observed, but is likely not the only inflammatory mechanism that modulates risk. Table. Clinical characteristics of study cohort stratified by the presence of CLS-B Citation Format: Andrea V. Barrio, Giacomo Montagna, Varadan Sevilimedu, Ethan Gomez, Dilip Giri, Babak Mehrara, Monica Morrow. Does Breast Inflammation Contribute to Lymphedema Risk in Patients Treated with Axillary Lymph Node Dissection? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-09.

e12620 Background: Neoadjuvant chemotherapy (NAC) is commonly utilized in women with locally advanced breast cancer, usually followed by surgery and radiation therapy (RT). Many studies aimed to address the risk factors contributing to a higher incidence of lymphedema in patients with breast cancer. Our group previously reported the extent of surgery increases the risk of lymphedema. Adjuvant chemotherapy with taxane-based regimens are associated with an increased risk of lymphedema likely due an increase in interstitial extracellular fluid volume therefore resulting in fluid retention. This study aims to directly compare and characterize the risk of lymphedema in patients receiving paclitaxel versus docetaxel-based NAC. Methods: This is a retrospective study approved by our institutional review board. The study included women with breast cancer treated consecutively at our institution with taxane-based NAC followed by surgery and RT from 2006 to 2018. Patients and tumor characteristics including age, race, body mass index (BMI), clinical stage, hormone receptor, HER2 status, type of surgery, RT techniques, and type of NAC (Paclitaxel versus Docetaxel), and its association to risk of lymphedema were analyzed using univariable and multivariable binary logic regression tests. Lymphedema was assessed before RT and at follow up visits, and was identified by >2.0-cm increase in arm circumference, or >10% increase in limb volume, or new self-reported lymphedema symptoms. Results: A total of 263 patients treated with either paclitaxel or docetaxel-based NAC were identified and analyzed. At a median follow up of 28.4 months (range 3.5-158.7 months). 26.2% (69/263) of patients developed lymphedema. On a multivariable analysis, patients who underwent axillary lymph node dissection (ALND) had a significantly higher rate of lymphedema (42.6%) compared to those who had only a sentinel lymph node biopsy (SLNB, 10.5%, p<0.05). Regardless of the type of surgery, there was no significant difference in rates of lymphedema between patients who received paclitaxel versus docetaxel-based NAC (28.7% vs 21.3%). However, among high-risk patients who underwent mastectomy with ALND, NAC with Paclitaxel was associated with a significantly higher rate of lymphedema compared to docetaxel (56.8% vs 22.7%, RR 2.50, p<0.05). Conclusions: This represents one of the largest studies examining the impact of taxane-based NAC on the risk of lymphedema in women with breast cancer. In this study, paclitaxel-based NAC was associated with a significantly higher risk of lymphedema in women who underwent mastectomy and ALND compared to docetaxel based chemotherapy. A larger, balanced, prospective study is warranted to verify this previously unidentified lymphedema risk from paclitaxel and guide individualized NAC decision.

Axillary lymph node dissection (ALND) and radiation therapy (RT) are commonly recommended for mastectomy patients with positive sentinel lymph node biopsy (SLNB). Effective alternatives to ALND that reduce lymphedema risk are needed. We evaluated rates of lymphedema in mastectomy patients who received SLNB with RT, compared to ALND with or without RT. 627 breast cancer patients who underwent 664 mastectomies between 2005 and 2013 were prospectively screened for lymphedema, median 22.8 months follow-up (range 3.0-86.9). Each mastectomy was categorized as SLNB-no RT, SLNB + RT, ALND-no RT, or ALND + RT. RT included chest wall ± nodal radiation. Perometer arm volume measurements were obtained pre- and post-operatively. Lymphedema was defined as ≥10 % arm volume increase. Kaplan-Meier and Cox regression analyses were performed to determine lymphedema rates and risk factors. Of 664 mastectomies, 52 % (343/664) were SLNB-no RT, 5 % (34/664) SLNB + RT, 9 % (58/664) ALND-no RT, and 34 % (229/664) ALND + RT. The 2 year cumulative lymphedema incidence was 10.0 % (95 % CI 2.6-34.4 %) for SLNB + RT compared with 19.3 % (95 % CI 10.8-33.1 %) for ALND-no RT, and 30.1 % (95 % CI 23.7-37.8 %) for ALND + RT. The lowest cumulative incidence was 2.19 % (95 % CI 0.88-5.40 %) for SLNB-no RT. By multivariate analysis, factors significantly associated with increased lymphedema risk included RT (p = 0.0017), ALND (p = 0.0001), greater number of lymph nodes removed (p = 0.0006), no reconstruction (p = 0.0418), higher BMI (p < 0.0001) and older age (p = 0.0021). In conclusion, avoiding completion ALND and instead receiving SLNB with RT may decrease lymphedema risk in patients requiring mastectomy. Future trials should investigate the safety of applying the ACOSOG Z0011 protocol to mastectomy patients.

The goal of this study was to investigate the association between blood draws, injections, blood pressure readings, trauma, cellulitis in the at-risk arm, and air travel and increases in arm volume in a cohort of patients treated for breast cancer and screened for lymphedema. Between 2005 and 2014, patients undergoing treatment of breast cancer at our institution were screened prospectively for lymphedema. Bilateral arm volume measurements were performed preoperatively and postoperatively using a Perometer. At each measurement, patients reported the number of blood draws, injections, blood pressure measurements, trauma to the at-risk arm(s), and number of flights taken since their last measurement. Arm volume was quantified using the relative volume change and weight-adjusted change formulas. Linear random effects models were used to assess the association between relative arm volume (as a continuous variable) and nontreatment risk factors, as well as clinical characteristics. In 3,041 measurements, there was no significant association between relative volume change or weight-adjusted change increase and undergoing one or more blood draws (P = .62), injections (P = .77), number of flights (one or two [P = .77] and three or more [P = .91] v none), or duration of flights (1 to 12 hours [P = .43] and 12 hours or more [P = .54] v none). By multivariate analysis, factors significantly associated with increases in arm volume included body mass index ≥ 25 (P = .0236), axillary lymph node dissection (P < .001), regional lymph node irradiation (P = .0364), and cellulitis (P < .001). This study suggests that although cellulitis increases risk of lymphedema, ipsilateral blood draws, injections, blood pressure readings, and air travel may not be associated with arm volume increases. The results may help to educate clinicians and patients on posttreatment risk, prevention, and management of lymphedema.

Axillary lymph node dissection (ALND) is recommended for patients with clinically node-positive breast cancer and carries a risk of lymphedema>30%. Patients with node-positive breast cancer may consider neoadjuvant chemotherapy, which can reduce node positivity. We sought to determine if neoadjuvant chemotherapy reduced the risk of lymphedema in patients undergoing ALND for node-positive breast cancer. The 229 patients who underwent unilateral ALND and chemotherapy were divided into two groups: 30% (68/229) had neoadjuvant and 70% (161/229) had adjuvant chemotherapy. Prospective arm volumes were measured via perometry preoperatively and at 3- to 7-month intervals after surgery. Lymphedema was defined as relative volume change (RVC)≥10%, >3 months from surgery. Kaplan-Meier curves and multivariate regression models were used to identify risk factors for lymphedema. Fifteen percent (10/68) of neoadjuvant patients compared with 23% (37/161) of adjuvant patients developed RVC≥10% (hazard ratio=0.76, p=0.39). For all patients, body mass index was significantly associated with lymphedema (p=0.0003). For neoadjuvant patients, residual lymph node disease after chemotherapy was associated with a ninefold greater risk of lymphedema compared to those without residual disease (p=0.038). Patients who underwent neoadjuvant chemotherapy did not have a statistically significant reduction in risk of lymphedema. Among patients who receive neoadjuvant chemotherapy, residual lymph node disease predicted a greater risk of lymphedema. These patients should be closely monitored for lymphedema and possible early intervention for the condition.

Identifying risk factors for lymphedema in patients treated for breast cancer has become increasingly important, given the current lack of standardization surrounding diagnosis and treatment. Reports on the association of body mass index (BMI) and weight change with lymphedema risk are conflicting. We sought to examine the impact of pre-operative BMI and post-treatment weight change on the incidence of lymphedema. From 2005 to 2011, 787 newly diagnosed breast cancer patients underwent prospective arm volume measurements with a Perometer pre- and post-operatively. BMI was calculated from same-day weight and height measurements. Lymphedema was defined as a relative volume change (RVC) of ≥ 10 %. Univariate and multivariate Cox proportional hazards models were used to evaluate the association between lymphedema risk and pre-operative BMI, weight change, and other demographic and treatment factors. By multivariate analysis, a pre-operative BMI ≥ 30 was significantly associated with an increased risk of lymphedema compared to a pre-operative BMI <25 and 25- <30 (p = 0.001 and p = 0.012, respectively). Patients with a pre-operative BMI 25- <30 were not at an increased risk of lymphedema compared to patients with a pre-operative BMI <25 (p = 0.409). Furthermore, a cumulative absolute weight fluctuation of 10 pounds gained/lost per month post-operatively significantly increased risk of lymphedema (HR: 1.97, p = < 0.0001). In conclusion, pre-operative BMI of ≥ 30 is an independent risk factor for lymphedema, whereas a BMI of 25- <30 is not. Large post-operative weight fluctuations also increase risk of lymphedema. Patients with a pre-operative BMI ≥ 30 and those who experience large weight fluctuations during and after treatment for breast cancer should be considered at higher-risk for lymphedema. Close monitoring or early intervention to ensure optimal treatment of the condition may be appropriate for these patients.

Arm lymphedema is a feared and presently incurable complication of breast cancer surgery and radiation treatment (RT). Lymphedema results from excess interstitial fluid accumulation, which leads to limb swelling and eventual tissue fibrosis that can cause lifelong impairment of arm use. Lymphedema concerns take center stage at many, if not the majority, of preoperative and postoperative consultations with patients who are undergoing breast cancer surgery, given that this complication can permanently harm quality of life, from both a physical/functional perspective as well as a psychosocial one. Findings from a 2013 systematic review and meta-analysis of 72 studies revealed an estimated 17% risk of arm lymphedema among patients with breast cancer, with risk increasing up to 2 years after surgery. The risk was four times higher in women who had a complete axillary lymph node dissection (ALND; 20%) versus those who had sentinel lymph node biopsy alone (5.6%). Among women who receive adjuvant RT after ALND, lymphedema risk is significantly higher. In a 2001 systematic review, the rate of lymphedema among women who underwent surgery plus axillary RT was an alarming 41%. Aside from treatment-related risk factors, a number of patient or disease-related risk factors exist for the development of lymphedema. Postoperative infection or delayed wound healing is associated with heightened lymphedema risk. A much more prevalent risk factor is obesity (body mass index 30 kg/m), which portends a nearly three-fold increase in risk for lymphedema. According to 2009/2010 Centers for Disease Control and Prevention statistics, 36% of all women and 42% of women age 60 years or older are obese in the United States. In the current era, with widening adoption of the findings of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, incidence of lymphedema should decline, given that we see decreasing rates of completion ALND among a subset of women undergoing breast-conserving therapy. However, there remains a large population of patients with node-positive disease for whom ALND is still indicated, including those with clinically positive nodes, locally advanced disease, those receiving neoadjuvant chemotherapy, and those undergoing mastectomy. Hence, research into the treatment of this chronic condition remains an important public health issue. Because many lymphedema risk factors are not modifiable, attention has largely been directed at treatment. To this aim, a number of studies have compared efficacy of various treatment options for lymphedema. Treatment options include, alone or in combination, exercise, skin care, compression bandaging, compression garments, manual therapy (massage), laser therapy, and pneumatic pumps. Complex decongestive therapy (CDT) incorporates manual lymphatic drainage, daily bandaging, exercise, and skin care. A systematic review of these therapies was published in 2006 and found that, in general, more intensive treatment by health professionals, such as CDT or manual lymphatic drainage, produced larger volume reductions than therapies undertaken by the patient, such as compression bandaging, exercise, or skin care. Studies of CDT showed an estimated 43% reduction in arm volume compared with only 11% with compression alone. However, excitement over CDT has been tempered by subsequent randomized trials that have thus far failed to demonstrate a significant benefit of CDT over standard compression therapy. In one trial by McNeely et al, 50 women were randomly assigned to 4 weeks of CDT or compression alone. Arm volume decreased significantly with both treatments, but no difference was observed between groups (46% CDT v 39% compression alone; P .22). This study was limited in follow-up to 1 month and did not assess quality-of-life parameters associated with treatment of lymphedema. Another trial by Andersen et al randomly assigned 42 women with lymphedema to CDT versus compression, and observed patients for 12 months. They also found no significant difference in arm volume reduction over the 12-month period between CDT and compression groups (48% v 60%, respectively; P .66). Armed with these data, one might question why yet another randomized controlled trial was necessary to examine this question. Limitations of the above trials included their small size, singleinstitution setting (and sometimes, even single CDT provider), and lack of long-term follow-up. In the article that accompanies this editorial, Dayes et al address all of these limitations in their eloquently designed, randomized, multicenter trial of CDT versus compression bandaging alone for patients with lymphedema. Dayes et al randomly assigned 103 women from six Canadian cancer centers to either CDT or compression bandaging between 2003 and 2009. Type and duration of CDT were standardized across groups, as were arm measurement techniques. Diary logs were JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 31 NUMBER 30 OCTOBER 2

Multiple lymphatic-venous anastomoses in reducing the risk of lymphedema in melanoma patients undergoing complete lymph node dissection. A retrospective case-control study

Prophylactic use of compression sleeves reduces the incidence of arm swelling in women at high risk of breast cancer–related lymphedema, according to results from a randomized controlled trial (RCT). The findings were reported in the Journal of Clinical Oncology.1 In the study, researchers from the University of Sydney in Australia and Tata Memorial Hospital in Parel, Mumbai, India, set out to determine whether prophylactic use of compression sleeves prevents arm swelling in women who have undergone axillary lymph node dissection (ALND) for breast cancer surgery. A total of 307 women were randomized to either receive usual postoperative care or usual care plus 2 compression sleeves to wear until 3 months following completion of adjuvant therapy. The researchers measured arm swelling, time free from arm swelling, and incidence of swelling. They also had patients complete the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the breast cancer–specific (BR23) questionnaire in order to measure the time to the first minimally important difference. “Lymphedema is a very prevalent and concerning symptom after cancer treatment where lymph nodes are involved. Thus, anything to prevent it is great. This study adds important evidence to the ability of compressive sleeves to prevent arm lymphedema,” says Electra Paskett, PhD, who holds the Marion N. Rowley Chair of Cancer Research and is the director of the Center for Cancer Health Equity at the James Cancer Hospital at The Ohio State University in Columbus. She notes, however, that there are a few issues. The first, she says, is cost. The sleeves are not inexpensive, and she says that many insurance plans do not cover them. Second, Dr. Paskett believes that a trained lymphedema provider should fit the sleeve. “And third, what was adherence to wearing the sleeve? I did an RCT study for lymphedema prevention, and the main issue was poor adherence,” says Dr. Paskett. “This was a very pragmatic trial in a setting in which lymphedema is common [advanced breast cancers with positive nodes], so that the risk for lymphedema is high,” says Patricia Ganz, MD, director of cancer prevention and control research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. “There are concerns that they did not report the length of time women had to wear the sleeves. The authors say, ‘instructed to wear them from the first postoperative day until 3 months after completion of adjuvant treatments.’ Three months after completion of treatment could be 9 months after surgery. So, the findings could be influenced by nearly continuous use of the compression sleeve.” Asked whether she would recommend the sleeve in women undergoing ALND, Dr. Ganz says she would need to see a more detailed analysis to understand which patients in this study benefited and whether benefit is sustained beyond 1 year. “While there is a measured difference, this did not seem to affect how women assessed their arm function, so this may not be a major benefit,” says Dr. Ganz. “This study is particularly useful because it evaluated the use of compression sleeves as a preventive strategy in women treated with axillary dissection, who are at the highest risk of developing lymphedema, and showed a reduction in lymphedema development at 1 year.” —Andrea Barrio, MD

Axillary-Lateral Thoracic Vessel Juncture Radiotherapy Dose Constraints for Predicting Long-Term Lymphedema Risk in Patients with Breast Cancer

Knowledge about long-term consequences of breast cancer treatment on shoulder and arm function and volume in stages I-II breast cancer survivors is limited. The effects of shoulder-arm function shortly after surgery on long-term function are unknown. One hundred and ninety-four women were examined pre-surgery (T0) and 6 weeks after surgery (T1). Of those, 110 were re-examined 7 years later (T2). Thirty-four women underwent sentinel lymph node biopsy (SLNB) and 76 underwent axillary lymph node dissection (ALND). Differences between affected and unaffected side were calculated for four ranges of motion functions, three strength functions and arm volume. These were used to analyse time and group effects. Differences exceeding 20° in range of motion, 20 % in strength and 200 ml in arm volume were considered clinically relevant. Multivariate regression analyses examined the effect of shoulder-arm function at T1 on shoulder-arm function at T2. Additional predictor variables included were age, follow-up time, Body Mass Index, complications, chemotherapy, radiation, SLNB/ALND and type of breast surgery. At T2, range of motion (except external rotation), abduction strength and arm volume were impaired compared to T0. After ALND, women had significantly more forward flexion impairment, increased arm volume and clinically relevant impairments (70 %) than after SLNB (41 %). T1 external rotation, abduction-external rotation, grip strength and arm volume were the strongest predictors of these variables at T2. Age was the strongest predictor of the remaining four variables. ALND predicted arm volume only. Seven years after breast cancer surgery, two-fifth of the women after SLNB and seven out of ten women after ALND had impairments. Impairments were found in five of eight shoulder-arm functions. After SLNB, women have less forward flexion impairment and less arm volume increase than after ALND. Shoulder-arm function at 6 weeks after surgery and age are the strongest predictors of long-term shoulder-arm function.

ObjectiveUpper limb lymphedema is one of the most common adverse events related to surgery owing to the large gap between guideline implementation and the intended clinical outcomes. However, the monitoring of limb lymphedema remains challenging because of vague clinical presentations. This study aimed to develop and validate practical predictive models for upper limb lymphedema through machine learning.MethodsWe retrospectively collected clinical data to develop models for early risk prediction of upper limb lymphedema based on a single-center electronic health record data from patients who underwent breast cancer surgery from June 2021 through June 2023. For prediction model building, 70% and 30% of the data were randomly split into training and testing sets, respectively. We then developed an upper limb lymphedema prediction model using machine learning algorithms, which included random forest model (RFM), generalized logistic regression model (GLRM), and artificial neural network model (ANNM). For evaluating the model’s performance, we used the area under the receiver operating characteristic curve (AUROC), calibration curve to compare different models. The potential clinical usefulness of the best model at the best threshold was assessed through a net benefit approach using a decision curve analysis (DCA).ResultsOf the 3201 patients screened for eligibility, 3160 participants were recruited for the prediction model. Among these, Body Mass Index (BMI), hypertension, TNM, lesion site, level of lymph node dissection(LNMD), treatment, and nurse were independent risk factors for upper limb lymphedema and were listed as candidate variables of ML-based prediction models. The RFM algorithm, in combination with seven candidate variables, demonstrated the highest prediction efficiency in both the training and internal verification sets, with an area under the curve (AUC) of 0.894 and 0.889 and a 95% confidence interval (CI) of 0.839–0.949 and 0.834–0.944, respectively. The other two types of prediction models had prediction efficiencies between AUCs of 0.731 and 0.819 and 95% CIs of 0.674–0.789 and 0.762–0.876, respectively.ConclusionThe interpretable predictive model helps physicians more accurately predict the upper limb lymphedema risk in patients undergoing breast cancer surgery. Especially for the RFM, this newly established machine learning-based model has shown good predictive ability for distinguishing high risk of upper limb lymphedema, which could facilitate future clinical decisions, hospital management, and improve outcomes.

Validity for the Simplified Water Displacement Instrument to Measure Arm Lymphedema as a Result of Breast Cancer Surgery

Patients undergoing axillary lymph node dissection (ALND) for breast cancer face a high risk of lymphedema, further increased by high body mass index (BMI) and insulin resistance. GLP-1 receptor agonists (GLP-1RAs) have the potential to reduce these risk factors, but their role in lymphedema has never been investigated. The purpose of this study was to determine if GLP-RAs can reduce the risk of lymphedema in patients undergoing ALND. All patients who underwent ALND at a tertiary cancer center between 2010 and 2023 were reviewed. Patients with less than 2years of follow-up from the time of ALND were excluded. Race, BMI, radiation, chemotherapy history, pre-existing diagnosis of diabetes, lymphedema development after ALND, and the use of GLP-1RAs were analyzed. Multivariate logistic regression analysis was performed to assess if there was a significant reduction in the risk of developing lymphedema after ALND. A sub-group analysis of non-diabetic patients was also performed. 3,830 patients who underwent ALND were included, 76 of which were treated with. GLP-1 RAs. The incidence of lymphedema in the GLP-1 RA cohort was 6.6% (5 patients). Compared to 28.5% (1,071 patients) in the non-GLP-1 RA cohort. On multivariate regression analysis, patients who were treated with GLP-1 RA were 86% less likely to develop lymphedema compared to the non-GLP-1 RA cohort (OR 0.14, 95% CI 0.04-0.32, p < 0.0001). A BMI of 25kg/m 2 or greater was a statistically significant risk factor for developing lymphedema with an odds ratio of 1.34 (95% CI 1.16-1.56, p < 0.0001). Diabetes was associated with lymphedema development that closely approached statistical significance (OR 1.32, 95% CI 0.97-1.78, p = 0.06). A subgroup analysis solely on non-diabetic patients showed similar results. The odds of developing lymphedema were 84% lower for patients without diabetes treated with GLP1-RAs compared to those who did not receive GLP-1 RAs (OR 0.16, 95% CI 0.05-0.40, p < 0.0001). GLP1-RAs appear to significantly reduce the risk of lymphedema in patientsundergoing ALND. The mechanism of action may be multifactorial and not limited to weight reduction and insulin resistance. Future prospective analysis is warranted to clarify the role of GLP-1RAs in reducing lymphedema risk.