Screening for Breast Cancer-Related Lymphedema: A Cross-Sectional Study Using Ultrasound and Bioelectrical Impedance Analysis

Screening for Breast Cancer-Related Lymphedema: A Cross-Sectional Study Using Ultrasound and Bioelectrical Impedance Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Screening for Breast Cancer-Related Lymphedema: A Cross-Sectional Study Using Ultrasound and Bioelectrical Impedance Analysis Jialin Fan, Yu Qu, Yujuan Liu, Yurong Zhang, Die Sang, Xin Zhang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7414488/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Breast cancer-related lymphoma (BCRL) develops in 25% of breast cancer patients following treatment. It is a chronic condition where swelling persists despite interventions like compression hosiery and manual lymphatic drainage. Aim This study aimed to determine factors associated with early-stage lymphedema in women with breast cancer, investigate the relationship between lymphedema, lymphatic flow velocity, and body composition, and explore potential mechanisms for preventing BCRL. Design: Cross-sectional study. Setting: Inpatient rehabilitation unit Population: Thirty-four female patients with confirmed BCRL (age: 49.6 ± 8.7 years; height: 158.6 ± 4.1 cm; weight: 60.2 ± 9.8 kg) and 26 healthy controls (age: 50.5 ± 15.1 years; height: 160.9 ± 5.9 cm; weight: 62.9 ± 10.1 kg) were enrolled between 2024 and 2025. Methods Lymphatic duct diameter and flow velocity at the right venous angle were measured using ultrasound. Hand grip strength was assessed using a dynamometer, and body composition was analyzed using a bioimpedance analyzer (InBody 770; InBody Co., Seoul, Korea). Statistical analyses included paired t-tests to compare BCRL and control groups and Spearman's correlation for associations between clinical characteristics. Receiver operating characteristic analysis was used to determine diagnostic thresholds for BCRL. Results Compared to healthy controls, the BCRL group showed significantly higher lymphatic flow velocity, lower phase angle, and reduced grip strength (all p < 0.01). Age was positively correlated with extracellular water (ECW) but negatively with phase angle, while grip strength was positively correlated with phase angle. The optimal diagnostic cutoffs for lymphedema were: lymphatic flow velocity ≥ 7.7 cm/s (35.3% sensitivity, 96.2% specificity), phase angle ≤ 4.05° (92.3% sensitivity, 70.6% specificity), and grip strength ≤ 18.1 N (88.5% sensitivity, 67.6% specificity). Conclusion Increased lymphatic flow velocity, decreased phase angle, and reduced grip strength were significant early-stage indicators of BCRL. Clinical rehabilitation impact: Identifying early risk factors for lymphedema can help clinicians understand its mechanism and enable timely interventions to prevent its progression. lymphedema risk factors breast cancer ultrasound phase angle Figures Figure 1 Background Breast cancer is the second leading cause of cancer-related deaths in women, accounting for 25% of all global female cancer diagnoses [ 1 , 2 ]. In some developed countries, the 5-year relative survival rate for breast cancer patients exceeds 80%, due to early prevention and advancements in treatment [ 3 ]. Breast cancer-related lymphedema (BCRL) is one of the most common and disabling complications in patients with breast cancer. It results from the accumulation of protein-rich interstitial fluid, leading to progressive limb swelling. Common symptoms include arm swelling, pain, and heaviness, which impair physical function, psychosocial well-being, and quality of life [ 4 ]. Moreover, lymphedema is a chronic condition, where swelling persists for years despite treatments like compression hosiery, manual lymphatic drainage, and others [ 5 ]. Research has identified several risk factors for BCRL, including young age, obesity, smoking, comorbidities like collagen disease and hypertension, advanced cancer stage, total mastectomy, axillary dissection, higher levels of axillary node excision, and surgical complications such as postoperative bleeding or infection. Chemotherapy also increases risk. [ 6 ]. However, as BCRL cannot be cured, early diagnosis, particularly in the early stages of lymphedema, and exploration of its underlying mechanisms are crucial [ 7 ]. High-resolution ultrasonography has been used to assess the diameters, structures, and chyle flow of lymphatic vessels. BCRL is no longer considered to be a result of lymphatic obstruction, as recent studies have identified failed peripheral lymphatic function as a principal contributing factor [ 8 ]. This study aims to determine the diameter and flow velocity of lymphatic vessels in patients with lymphedema using ultrasonographic imaging. Additionally, handgrip strength in the affected hand is often reduced compared to the unaffected side. Radiotherapy may also impair muscle metabolism, leading to muscle wasting and declines in strength and function [ 9 ]. In mild-to-moderate BCRL, the affected limb exhibits subtle volume changes that tape circumference measurement (TVM) may overlook. Bioelectrical impedance analysis (BIA), which used the phase angle (PhA) to assess cellular integrity, has emerged as an effective tool for quantifying BCRL volume [ 10 ]. The objective of this study is to identify early variations in lymphedema, facilitating timely intervention to prevent its manifestation. Materials and Methods Participants and setting This cross-sectional study enrolled 34 female patients (aged > 18 years) with right breast cancer who underwent modified radical mastectomy at Beijing Chaoyang District Sanhuan Cancer Hospital between 2024–2025, alongside 26 healthy control volunteers. All participants provided informed consent. Inclusion criteria were right breast cancer (diagnosed according to the Chinese Anti-Cancer Association guidelines) presenting with stage 0-I lymphedema after axillary lymph node dissection. Exclusion criteria included severe comorbidities, contraindications to ultrasound examination, secondary lymphedema from other malignancies, tumor metastasis, or upper extremity thrombosis. Assessments Grip strength examination Maximal handgrip strength was measured using a hand dynamometer. Participants were seated with their upper arm adjacent the torso and the elbow fully extended. Three trials were performed with the right hand, and the mean value was recorded. Sonographic examination Half an hour postprandial, patients were placed in the supine position. Using color Doppler ultrasonography (PHILIPS EPIQ 5, Netherlands), we measured the diameter and flow velocity of lymphatic ducts at the right venous angle. Body composition measurements Anthropometric indices were measured using a bio-impedance analyzer (BIA; InBody 770; InBody Co., Seoul, Korea). Participants were instructed to avoid excessive fluid intake, alcohol, and strenuous physical activity before assessment. Subjects removed metallic items, stood barefoot on the analyzer's foot electrodes, and lightly gripped the hand electrodes. The BIA recorded body mass index (BMI), muscle mass, muscle proportion, extracellular water ratio (ECW/TBW), PhA, and bioelectrical impedance (at 5 kHz). Statistical analysis Statistical analyses were conducted using SPSS software (version 26.0), with a significance threshold set at p < 0.05. Data were reported as mean (standard deviation [SD]). Depending on the Shapiro-Wilk normality test results, either independent sample t-tests or Mann-Whitney U tests were applied to continuous variables for intergroup comparison. Receiver operating characteristic (ROC) analysis assessed the diagnostic ability of lymphatic flow velocity, grip strength, and phase angle in distinguishing BCRL patients from controls. Results Table 1 Subject characteristics Study Group Age (years) Height (cm) Weight(kg) Control Group (n = 26) 50.5 ± 15.1 160.9 ± 5.9 62.9 ± 10.1 Lymphedema Group (n = 34) 49.6 ± 8.7 158.6 ± 4.1 60.2 ± 9.8 Values are presented as the mean ± (SD). The demographic characteristics of the subjects are shown in Table 1 . A total of 60 participants completed the study, consisting of 34 women with right-sided lymphedema (age: 49.6 ± 8.7 years, height: 158.6 ± 4.1 cm, weight: 60.2 ± 9.8 kg) and 26 healthy control (age: 50.5 ± 15.1 years, height: 160.9 ± 5.9 cm, weight: 62.9 ± 10.1 kg). The groups were similar in physical characteristics (p age = 0.776, p height : 0.091, p weight : 0.293). Comparisons of ultrasound-and physiologically measured variables between women with right lymphedema and healthy individuals are shown in Table 2 . Lymphatic flow velocity was significantly higher in the lymphedema group relative to controls (p = 0.019); however, lymphatic diameter did not differ significantly between the groups. Additionally, grip strength (p = 0.000) and phase angle (p = 0.000) were lower in the lymphedema group than in the control group. Table 2 Comparison of measured variables between groups Variable Control Group (n = 26) Lymphedema Group (n = 34) p -value Lymphatic flow velocity 12.53 ± 3.70 15.69 ± 6.29 0.019** Lymphatic diameter 0.11 ± 0.02 0.11 ± 0.03 0.623 Grip strength 23.45 ± 4.81 16.92 ± 6.07 0.000** Phase angle 4.70 ± 0.50 3.81 ± 0.56 0.000** Impedance ratio at 5 kHz 1.01 ± 0.02 1.09 ± 0.23 0.055 The correlations between sonographic and BIA measurements are summarized in Table 3 . Specifically, ECW ratio had a significant negative correlation with phase angle (Spearman rho = − 0.430, p < 0.01), and a positive correlation with age (Spearman rho = 0.412, p < 0.01) and lymphatic diameter (Spearman rho = 0.261, p < 0.05). The phase angle was positively correlated with grip strength (Spearman rho = 0.567, p < 0.01) but negatively correlated with age (Spearman rho = − 0.262, p < 0.05) and impedance ratio at 5 kHz (Spearman rho = − 0.368, p < 0.01). ROC curve analysis identified the following cut-off values for distinguishing lymphedema patients from healthy controls: phase angle 4.05° (sensitivity = 92.3%, specificity = 70.6%); lymphatic flow velocity 17.7cm/s (sensitivity = 35.3%, specificity = 96.2%); and grip strength 18.1 N (sensitivity = 88.5%, specificity = 67.6% ). The area under the curve (AUC) values were: phase angle-AUC = 0.8829; lymphatic flow velocity-AUC = 0.6510; and grip strength-AUC = 0.8026. Discussion This study provides novel insights into the early detection of BCRL by simultaneously evaluating lymphatic flow dynamics via ultrasound and cellular integrity/body composition via BIA. Our findings demonstrate significant alterations in lymphatic flow velocity, phase angle (PhA), and grip strength in patients with early-stage BCRL, suggesting potential objective indicators for screening. The etiology of lymphedema remains poorly understood, but lymph node removal and radiation therapy are thought to impair the lymphatic system’s ability to transport excess fluid and macromolecules away from tissues back to the blood vasculature [ 11 ]. The most striking observation in this study was the significantly increased lymphatic flow velocity at the right venous angle in the BCRL group. While this may seem counterintuitive—since lymphedema is associated with fluid accumulation—this aligns with emerging evidence suggesting that BCRL involves more than just lymphatic vessel obstruction. Our results support the concept of failing peripheral lymphatic function [ 12 ], where initial damage to peripheral lymphatics (from surgery or radiotherapy) leads to increased interstitial filtration rate, overwhelming the system’s drainage capacity. This compensatory hyperactivity could be an early subclinical sign of lymphatic stress, preceding overt swelling detectable by traditional methods such as tape measurement. However, the low sensitivity (35.3%) of the lymphatic flow velocity cutoff (≥ 17.7 cm/s), despite its high specificity (96.2%), suggests that while it is a specific indicator, it may miss early cases when used alone. The lack of significant difference in lymphatic diameter further supports the idea that structural changes in the later stages of lymphedema, detectable by ultrasound, might occur later than functional alterations in flow dynamics in the early lymphedema stage. Previous studies have found lymphatic architectural abnormalities in both the affected and unaffected arms of patients with BCRL [ 11 ], suggesting that the promotion of lymphangiogenesis and lymphatic vessel remodeling is critical for restoring tissue fluid drainage and treating secondary lymphedema [ 13 ]. The significant reduction in phase angle (PhA) in the BCRL group is equally important. PhA, derived from BIA, reflects changes in fluid balance, cellular membrane integrity, and cellular function, serving as an indicator of cellular health [ 14 ]. The markedly lower PhA in patients with BCRL strongly suggests early changes in fluid distribution and cellular function. This is corroborated by the significant negative correlation between PhA and ECW, indicating that as PhA decreases, the proportion of fluid trapped outside the cells increases—a hallmark of lymphedema, consistent with previous studies [ 10 ]. The high sensitivity (92.3%) and excellent AUC (0.883) of the PhA cutoff (≤ 4.05°) highlight its potential as a highly sensitive screening tool for early BCRL, capable of identifying patients before significant arm volume changes occur. Additionally, the positive correlation between PhA and grip strength (Spearman rho = 0.567, p < 0.01) further supports their combined use in early BCRL detection. This also aligns with evidence that PhA can serve as a prognostic indicator, such as predicting 6-month mortality in chronic conditions [ 15 ]. Reduced grip strength was another significant feature that differentiated the BCRL group. Handgrip strength is known to be severely affected by lymphedema secondary to breast cancer. Previous research has shown that reduced grip strength affects both power and precision of hand function, limiting activities like lifting heavy or bulky objects, writing, and simulated feeding [ 9 ]. Furthermore, radiotherapy may disrupt muscle metabolism, leading to muscle wasting and a decline in muscle strength and fitness [ 16 ]. The good sensitivity (88.5%) and AUC (0.803) of the grip strength cutoff (≤ 18.1 N) support its utility as a simple, functional marker for screening. The correlation analysis provides additional insights. The positive correlation between age and ECW, along with the negative correlation between age and PhA, suggests that older patients may be more prone to fluid dysregulation and cellular changes that increase the risk of BCRL. The positive correlation between BMI and muscle mass/muscle proportion reinforces the validity of the BIA measurements in assessing body composition. Limitations This study has several limitations. Its cross-sectional design prevents the establishment of causality. While the sample size is adequate to detect the main effects, it remains relatively small. The study’s focus on right-sided BCRL and specific measurement sites may limit the generalizability of the findings. Additionally, the use of 0-I classification, although targeting early stages, relies on clinical assessment, potentially missing the earliest subclinical changes. Conclusion The findings of this study suggest that increased lymphatic flow velocity (indicating compensatory central pumping), decreased phase angle (reflecting cellular dysfunction and fluid shifts), and reduced grip strength are key features of early-stage BCRL. The application of these screening markers could facilitate timely preventive interventions, ultimately improving patient outcomes and quality of life. Abbreviations BCRL Breast Cancer–Related Lymphedema PhA Phase Angle BMI Body Mass Index ECW Extracellular Water TBW Total Body Water BIA Bioelectrical Impedance Analysis ROC Receiver Operating Characteristic AUC Area Under the Curve SD Standard Deviation TVM Tape Circumference Measurement Declarations Ethical approval and consent to participate This study was performed in accordance with the guidelines of the Declaration of Helsinki. Ethical approval was granted by the Ethics Review Committee of the Sanhuan Cancer Hospital in Chaoyang District, Beijing (SH-2023036). All participants provided informed consent. Data availability statement The original contributions presented in this study are included in the article/supplementary material, and further inquiries can be directed to the corresponding author. Competing interests The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. Funding The authors declare that they received financial support for this research and publication of the article. This study was supported by the National Natural Science Foundation of China (No. 82372585). Author contributions JF: Data curation, Investigation, Writing, review, and editing. YQ: Formal analysis, writing the original draft, writing the review, and editing.YL:Data curation, Investigation.YZ:Data curation, Investigation.DS:Data curation, Investigation.XZ:Data curation, Investigation.MH:Data curation, Investigation.SS:Data curation, Investigation. MH: Data curation, Formal analysis, Investigation, Supervision, Writing, review and editing. References Sun, Y.-S., et al., Risk Factors and Preventions of Breast Cancer. International Journal of Biological Sciences, 2017. 13 (11): p. 1387-1397. Marotta, N., et al., Efficacy of kinesio taping on upper limb volume reduction in patients with breast cancer-related lymphedema: a systematic review of randomized controlled trials. Eur J Phys Rehabil Med, 2023. 59 (2): p. 237-247. DeSantis, C.E., et al., Breast cancer statistics, 2015: Convergence of incidence rates between black and white women. CA Cancer J Clin, 2016. 66 (1): p. 31-42. Ahn, H.R., et al., Incidence and risk factors of breast cancer-related lymphedema in Korea: a nationwide retrospective cohort study. Int J Surg, 2024. 110 (6): p. 3518-3526. Clark, B., J. Sitzia, and W. Harlow, Incidence and risk of arm oedema following treatment for breast cancer: a three-year follow-up study. QJM, 2005. 98 (5): p. 343-8. Konishi, T., et al., Risk factors for arm lymphedema following breast cancer surgery: a Japanese nationwide database study of 84,022 patients. Breast Cancer, 2023. 30 (1): p. 36-45. Sarri, A.J., et al., Lymphoscintigraphy detecting alterations of upper limb lymphatic flow following early sentinel lymph node biopsy in breast cancer. Breast Cancer (Dove Med Press), 2017. 9 : p. 279-285. Bates, D.O., An interstitial hypothesis for breast cancer related lymphoedema. Pathophysiology, 2010. 17 (4): p. 289-94. Shinde, S.B., et al., Estimation of Hand Function Impairment in Breast Cancer Survivors with Lymphedema. South Asian J Cancer, 2025. 14 (1): p. 23-29. Kim, W.J., et al., Feasibility of segmental bioelectrical impedance analysis for mild- to moderate-degree breast cancer-related lymphedema: Correlation with circumferential volume measurement and phase angle. Medicine (Baltimore), 2021. 100 (4): p. e23722. Aldrich, M.B., et al., Lymphatic abnormalities in the normal contralateral arms of subjects with breast cancer-related lymphedema as assessed by near-infrared fluorescent imaging. Biomed Opt Express, 2012. 3 (6): p. 1256-65. Modi, S., et al., Human lymphatic pumping measured in healthy and lymphoedematous arms by lymphatic congestion lymphoscintigraphy. J Physiol, 2007. 583 (Pt 1): p. 271-85. Li, N., et al., An arabinogalactan isolated from Cynanchum atratum promotes lymphangiogenesis and lymphatic vessel remodeling to alleviate secondary lymphedema. Int J Biol Macromol, 2024. 273 (Pt 2): p. 133061. Norman, K., et al., Bioelectrical phase angle and impedance vector analysis--clinical relevance and applicability of impedance parameters. Clin Nutr, 2012. 31 (6): p. 854-61. Norman, K., et al., Cutoff percentiles of bioelectrical phase angle predict functionality, quality of life, and mortality in patients with cancer. Am J Clin Nutr, 2010. 92 (3): p. 612-9. Clarkson, P.M. and S.A. Kaufman, Should resistance exercise be recommended during breast cancer treatment? Med Hypotheses, 2010. 75 (2): p. 192-5. Table 3 Table 3 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table3.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 15 Sep, 2025 Editor invited by journal 21 Aug, 2025 Editor assigned by journal 20 Aug, 2025 Submission checks completed at journal 20 Aug, 2025 First submitted to journal 20 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7414488","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":518751370,"identity":"70041b78-38a1-4d4d-99b3-3cadcf83b91f","order_by":0,"name":"Jialin Fan","email":"","orcid":"","institution":"Beijing Chaoyang District Sanhuan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jialin","middleName":"","lastName":"Fan","suffix":""},{"id":518751371,"identity":"0f721537-75a6-4ef8-be9b-549cc194bea8","order_by":1,"name":"Yu Qu","email":"","orcid":"","institution":"Qilu Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Qu","suffix":""},{"id":518751372,"identity":"0f4a172f-6624-4a91-8270-776a14760302","order_by":2,"name":"Yujuan Liu","email":"","orcid":"","institution":"Beijing Chaoyang District Sanhuan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yujuan","middleName":"","lastName":"Liu","suffix":""},{"id":518751373,"identity":"eee142bc-7641-4871-b822-1bcdb1efb96a","order_by":3,"name":"Yurong Zhang","email":"","orcid":"","institution":"Beijing Chaoyang District Sanhuan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yurong","middleName":"","lastName":"Zhang","suffix":""},{"id":518751374,"identity":"6ce4d118-b8df-4c1a-9c73-9cf97a390fb0","order_by":4,"name":"Die Sang","email":"","orcid":"","institution":"Beijing Chaoyang District Sanhuan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Die","middleName":"","lastName":"Sang","suffix":""},{"id":518751375,"identity":"ee135fc5-a498-4535-8d67-d136abe47f3c","order_by":5,"name":"Xin Zhang","email":"","orcid":"","institution":"Beijing Chaoyang District Sanhuan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Zhang","suffix":""},{"id":518751376,"identity":"55838754-27bd-482c-b664-7b5191f2a528","order_by":6,"name":"Miao He","email":"","orcid":"","institution":"Beijing Chaoyang District Sanhuan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Miao","middleName":"","lastName":"He","suffix":""},{"id":518751377,"identity":"dbdded66-9640-4bd1-a85d-80d57b62a258","order_by":7,"name":"Saixuan Shen","email":"","orcid":"","institution":"Beijing Chaoyang District Sanhuan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Saixuan","middleName":"","lastName":"Shen","suffix":""},{"id":518751378,"identity":"316851a0-f03c-4d38-80f1-ff9701de1156","order_by":8,"name":"Ming Huo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyElEQVRIiWNgGAWjYBACAxCRwMAgxw9mFJCgxViyAcQwIFYLECRuOIDMxQfMJZKPbni4o9bY+PzqxA8PDBjk+cUO4NdiOSMt7UbimeNyZjfebpYAOsxw5uwEAg67kWN2I7HtmLHZjbMbQFoSDG4TqSVx84yzm3+QoqUmcQN/7zYibTnzDOiXtgPGEjd4t1kkGEgQ4Zfjycdu/myrk+PvP7v55o8KG3l+aQJaoOAwA4MEWKUEUcpBoI6Bgf8A0apHwSgYBaNghAEAhL5L6t7ruRkAAAAASUVORK5CYII=","orcid":"","institution":"Beijing Chaoyang District Sanhuan Cancer Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ming","middleName":"","lastName":"Huo","suffix":""}],"badges":[],"createdAt":"2025-08-20 07:23:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7414488/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7414488/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":92048326,"identity":"5fc80ea2-5379-4521-87fa-33eaca135a0e","added_by":"auto","created_at":"2025-09-24 05:13:17","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":143902,"visible":true,"origin":"","legend":"","description":"","filename":"ScreeningforBreastCancerRelatedLymphedemaDevelopmentUsingUltrasoundandBioimpedanceanalyzer1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7414488/v1/6de3a5ddf4a265594649242e.docx"},{"id":92048321,"identity":"1f5f13c1-9ca0-428a-a7b5-f7ceea694c95","added_by":"auto","created_at":"2025-09-24 05:13:17","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":10493,"visible":true,"origin":"","legend":"","description":"","filename":"eeefc231a3fd4cc781d34c31fb878306.json","url":"https://assets-eu.researchsquare.com/files/rs-7414488/v1/7438e0dfaa488a6ecb81eb5d.json"},{"id":92048325,"identity":"b92dd067-2500-4b8d-97f9-bad5c1fc7d86","added_by":"auto","created_at":"2025-09-24 05:13:17","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":85003,"visible":true,"origin":"","legend":"","description":"","filename":"eeefc231a3fd4cc781d34c31fb8783061enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7414488/v1/4b903006ffa299d550460075.xml"},{"id":92048319,"identity":"c328d6c6-dc63-4bee-af08-de2cd2d86b59","added_by":"auto","created_at":"2025-09-24 05:13:17","extension":"jpeg","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":121779,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7414488/v1/6e583e791c6334e10763c4af.jpeg"},{"id":92048324,"identity":"927723b9-c3c9-457c-95ba-ea1a686170be","added_by":"auto","created_at":"2025-09-24 05:13:17","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":19146,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7414488/v1/c0299027ffb8bd29cd132f9a.png"},{"id":92063212,"identity":"b9978d51-62aa-4525-815d-d1292578c470","added_by":"auto","created_at":"2025-09-24 08:37:23","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":81805,"visible":true,"origin":"","legend":"","description":"","filename":"eeefc231a3fd4cc781d34c31fb8783061structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7414488/v1/fd69eb83ea7a6322cc1939c4.xml"},{"id":92063099,"identity":"84bbf089-02b6-420f-8ddd-8452c1f0a466","added_by":"auto","created_at":"2025-09-24 08:36:55","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":92055,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7414488/v1/32b89c7baf22eb40f9f0bad6.html"},{"id":92062936,"identity":"b874d9b7-e67d-4ce9-b016-258225431572","added_by":"auto","created_at":"2025-09-24 08:36:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":51341,"visible":true,"origin":"","legend":"\u003cp\u003eUnnumbered image in the Results section.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7414488/v1/9f4915f9c4609c5e31a05aa4.png"},{"id":92063545,"identity":"e6d1d300-68c1-40f8-8d39-39a5fc989035","added_by":"auto","created_at":"2025-09-24 08:38:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":665310,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7414488/v1/f93093c9-436f-4aa7-b3f5-c5a5872463b4.pdf"},{"id":92048323,"identity":"75de61d3-470f-46d0-bf3c-e3c46264bd28","added_by":"auto","created_at":"2025-09-24 05:13:17","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16616,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-7414488/v1/11a31647ab3a640258abc3aa.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Screening for Breast Cancer-Related Lymphedema: A Cross-Sectional Study Using Ultrasound and Bioelectrical Impedance Analysis","fulltext":[{"header":"Background","content":"\u003cp\u003eBreast cancer is the second leading cause of cancer-related deaths in women, accounting for 25% of all global female cancer diagnoses [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In some developed countries, the 5-year relative survival rate for breast cancer patients exceeds 80%, due to early prevention and advancements in treatment [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eBreast cancer-related lymphedema (BCRL) is one of the most common and disabling complications in patients with breast cancer. It results from the accumulation of protein-rich interstitial fluid, leading to progressive limb swelling. Common symptoms include arm swelling, pain, and heaviness, which impair physical function, psychosocial well-being, and quality of life [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Moreover, lymphedema is a chronic condition, where swelling persists for years despite treatments like compression hosiery, manual lymphatic drainage, and others [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eResearch has identified several risk factors for BCRL, including young age, obesity, smoking, comorbidities like collagen disease and hypertension, advanced cancer stage, total mastectomy, axillary dissection, higher levels of axillary node excision, and surgical complications such as postoperative bleeding or infection. Chemotherapy also increases risk. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, as BCRL cannot be cured, early diagnosis, particularly in the early stages of lymphedema, and exploration of its underlying mechanisms are crucial [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHigh-resolution ultrasonography has been used to assess the diameters, structures, and chyle flow of lymphatic vessels. BCRL is no longer considered to be a result of lymphatic obstruction, as recent studies have identified failed peripheral lymphatic function as a principal contributing factor [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This study aims to determine the diameter and flow velocity of lymphatic vessels in patients with lymphedema using ultrasonographic imaging.\u003c/p\u003e\u003cp\u003eAdditionally, handgrip strength in the affected hand is often reduced compared to the unaffected side. Radiotherapy may also impair muscle metabolism, leading to muscle wasting and declines in strength and function [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn mild-to-moderate BCRL, the affected limb exhibits subtle volume changes that tape circumference measurement (TVM) may overlook. Bioelectrical impedance analysis (BIA), which used the phase angle (PhA) to assess cellular integrity, has emerged as an effective tool for quantifying BCRL volume [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe objective of this study is to identify early variations in lymphedema, facilitating timely intervention to prevent its manifestation.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eParticipants and setting\u003c/h2\u003e\u003cp\u003eThis cross-sectional study enrolled 34 female patients (aged\u0026thinsp;\u0026gt;\u0026thinsp;18 years) with right breast cancer who underwent modified radical mastectomy at Beijing Chaoyang District Sanhuan Cancer Hospital between 2024\u0026ndash;2025, alongside 26 healthy control volunteers. All participants provided informed consent. Inclusion criteria were right breast cancer (diagnosed according to the Chinese Anti-Cancer Association guidelines) presenting with stage 0-I lymphedema after axillary lymph node dissection. Exclusion criteria included severe comorbidities, contraindications to ultrasound examination, secondary lymphedema from other malignancies, tumor metastasis, or upper extremity thrombosis.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eAssessments\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eGrip strength examination\u003c/h2\u003e\u003cp\u003eMaximal handgrip strength was measured using a hand dynamometer. Participants were seated with their upper arm adjacent the torso and the elbow fully extended. Three trials were performed with the right hand, and the mean value was recorded.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSonographic examination\u003c/h3\u003e\n\u003cp\u003eHalf an hour postprandial, patients were placed in the supine position. Using color Doppler ultrasonography (PHILIPS EPIQ 5, Netherlands), we measured the diameter and flow velocity of lymphatic ducts at the right venous angle.\u003c/p\u003e\n\u003ch3\u003eBody composition measurements\u003c/h3\u003e\n\u003cp\u003eAnthropometric indices were measured using a bio-impedance analyzer (BIA; InBody 770; InBody Co., Seoul, Korea). Participants were instructed to avoid excessive fluid intake, alcohol, and strenuous physical activity before assessment. Subjects removed metallic items, stood barefoot on the analyzer's foot electrodes, and lightly gripped the hand electrodes. The BIA recorded body mass index (BMI), muscle mass, muscle proportion, extracellular water ratio (ECW/TBW), PhA, and bioelectrical impedance (at 5 kHz).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analyses were conducted using SPSS software (version 26.0), with a significance threshold set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Data were reported as mean (standard deviation [SD]). Depending on the Shapiro-Wilk normality test results, either independent sample t-tests or Mann-Whitney U tests were applied to continuous variables for intergroup comparison. Receiver operating characteristic (ROC) analysis assessed the diagnostic ability of lymphatic flow velocity, grip strength, and phase angle in distinguishing BCRL patients from controls.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSubject characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy Group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHeight (cm)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWeight(kg)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eControl Group (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e50.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e160.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e62.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphedema Group (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e49.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e158.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e60.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eValues are presented as the mean \u0026plusmn; (SD).\u003c/p\u003e\u003cp\u003eThe demographic characteristics of the subjects are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 60 participants completed the study, consisting of 34 women with right-sided lymphedema (age: 49.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7 years, height: 158.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1 cm, weight: 60.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8 kg) and 26 healthy control (age: 50.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1 years, height: 160.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9 cm, weight: 62.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1 kg). The groups were similar in physical characteristics (p\u003csub\u003eage\u003c/sub\u003e = 0.776, p\u003csub\u003eheight\u003c/sub\u003e: 0.091, p\u003csub\u003eweight\u003c/sub\u003e: 0.293).\u003c/p\u003e\u003cp\u003eComparisons of ultrasound-and physiologically measured variables between women with right lymphedema and healthy individuals are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Lymphatic flow velocity was significantly higher in the lymphedema group relative to controls (p\u0026thinsp;=\u0026thinsp;0.019); however, lymphatic diameter did not differ significantly between the groups. Additionally, grip strength (p\u0026thinsp;=\u0026thinsp;0.000) and phase angle (p\u0026thinsp;=\u0026thinsp;0.000) were lower in the lymphedema group than in the control group.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of measured variables between groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl Group (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLymphedema Group (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphatic flow velocity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e12.53\u0026thinsp;\u0026plusmn;\u0026thinsp;3.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e15.69\u0026thinsp;\u0026plusmn;\u0026thinsp;6.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.019**\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphatic diameter\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.623\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrip strength\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e23.45\u0026thinsp;\u0026plusmn;\u0026thinsp;4.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e16.92\u0026thinsp;\u0026plusmn;\u0026thinsp;6.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.000**\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhase angle\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e4.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.000**\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImpedance ratio at 5 kHz\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.055\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe correlations between sonographic and BIA measurements are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Specifically, ECW ratio had a significant negative correlation with phase angle (Spearman rho\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.430, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and a positive correlation with age (Spearman rho\u0026thinsp;=\u0026thinsp;0.412, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and lymphatic diameter (Spearman rho\u0026thinsp;=\u0026thinsp;0.261, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The phase angle was positively correlated with grip strength (Spearman rho\u0026thinsp;=\u0026thinsp;0.567, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) but negatively correlated with age (Spearman rho\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.262, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and impedance ratio at 5 kHz (Spearman rho\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.368, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eROC curve analysis identified the following cut-off values for distinguishing lymphedema patients from healthy controls: phase angle 4.05\u0026deg; (sensitivity\u0026thinsp;=\u0026thinsp;92.3%, specificity\u0026thinsp;=\u0026thinsp;70.6%); lymphatic flow velocity 17.7cm/s (sensitivity\u0026thinsp;=\u0026thinsp;35.3%, specificity\u0026thinsp;=\u0026thinsp;96.2%); and grip strength 18.1 N (sensitivity\u0026thinsp;=\u0026thinsp;88.5%, specificity\u0026thinsp;=\u0026thinsp;67.6% ). The area under the curve (AUC) values were: phase angle-AUC\u0026thinsp;=\u0026thinsp;0.8829; lymphatic flow velocity-AUC\u0026thinsp;=\u0026thinsp;0.6510; and grip strength-AUC\u0026thinsp;=\u0026thinsp;0.8026.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides novel insights into the early detection of BCRL by simultaneously evaluating lymphatic flow dynamics via ultrasound and cellular integrity/body composition via BIA. Our findings demonstrate significant alterations in lymphatic flow velocity, phase angle (PhA), and grip strength in patients with early-stage BCRL, suggesting potential objective indicators for screening.\u003c/p\u003e\u003cp\u003eThe etiology of lymphedema remains poorly understood, but lymph node removal and radiation therapy are thought to impair the lymphatic system\u0026rsquo;s ability to transport excess fluid and macromolecules away from tissues back to the blood vasculature [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe most striking observation in this study was the significantly increased lymphatic flow velocity at the right venous angle in the BCRL group. While this may seem counterintuitive\u0026mdash;since lymphedema is associated with fluid accumulation\u0026mdash;this aligns with emerging evidence suggesting that BCRL involves more than just lymphatic vessel obstruction. Our results support the concept of failing peripheral lymphatic function [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], where initial damage to peripheral lymphatics (from surgery or radiotherapy) leads to increased interstitial filtration rate, overwhelming the system\u0026rsquo;s drainage capacity.\u003c/p\u003e\u003cp\u003eThis compensatory hyperactivity could be an early subclinical sign of lymphatic stress, preceding overt swelling detectable by traditional methods such as tape measurement. However, the low sensitivity (35.3%) of the lymphatic flow velocity cutoff (\u0026ge;\u0026thinsp;17.7 cm/s), despite its high specificity (96.2%), suggests that while it is a specific indicator, it may miss early cases when used alone. The lack of significant difference in lymphatic diameter further supports the idea that structural changes in the later stages of lymphedema, detectable by ultrasound, might occur later than functional alterations in flow dynamics in the early lymphedema stage. Previous studies have found lymphatic architectural abnormalities in both the affected and unaffected arms of patients with BCRL [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], suggesting that the promotion of lymphangiogenesis and lymphatic vessel remodeling is critical for restoring tissue fluid drainage and treating secondary lymphedema [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe significant reduction in phase angle (PhA) in the BCRL group is equally important. PhA, derived from BIA, reflects changes in fluid balance, cellular membrane integrity, and cellular function, serving as an indicator of cellular health [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The markedly lower PhA in patients with BCRL strongly suggests early changes in fluid distribution and cellular function. This is corroborated by the significant negative correlation between PhA and ECW, indicating that as PhA decreases, the proportion of fluid trapped outside the cells increases\u0026mdash;a hallmark of lymphedema, consistent with previous studies [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The high sensitivity (92.3%) and excellent AUC (0.883) of the PhA cutoff (\u0026le;\u0026thinsp;4.05\u0026deg;) highlight its potential as a highly sensitive screening tool for early BCRL, capable of identifying patients before significant arm volume changes occur. Additionally, the positive correlation between PhA and grip strength (Spearman rho\u0026thinsp;=\u0026thinsp;0.567, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) further supports their combined use in early BCRL detection. This also aligns with evidence that PhA can serve as a prognostic indicator, such as predicting 6-month mortality in chronic conditions [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eReduced grip strength was another significant feature that differentiated the BCRL group. Handgrip strength is known to be severely affected by lymphedema secondary to breast cancer. Previous research has shown that reduced grip strength affects both power and precision of hand function, limiting activities like lifting heavy or bulky objects, writing, and simulated feeding [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFurthermore, radiotherapy may disrupt muscle metabolism, leading to muscle wasting and a decline in muscle strength and fitness [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The good sensitivity (88.5%) and AUC (0.803) of the grip strength cutoff (\u0026le;\u0026thinsp;18.1 N) support its utility as a simple, functional marker for screening.\u003c/p\u003e\u003cp\u003eThe correlation analysis provides additional insights. The positive correlation between age and ECW, along with the negative correlation between age and PhA, suggests that older patients may be more prone to fluid dysregulation and cellular changes that increase the risk of BCRL. The positive correlation between BMI and muscle mass/muscle proportion reinforces the validity of the BIA measurements in assessing body composition.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eThis study has several limitations. Its cross-sectional design prevents the establishment of causality. While the sample size is adequate to detect the main effects, it remains relatively small. The study\u0026rsquo;s focus on right-sided BCRL and specific measurement sites may limit the generalizability of the findings. Additionally, the use of 0-I classification, although targeting early stages, relies on clinical assessment, potentially missing the earliest subclinical changes.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe findings of this study suggest that increased lymphatic flow velocity (indicating compensatory central pumping), decreased phase angle (reflecting cellular dysfunction and fluid shifts), and reduced grip strength are key features of early-stage BCRL. The application of these screening markers could facilitate timely preventive interventions, ultimately improving patient outcomes and quality of life.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBCRL\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBreast Cancer\u0026ndash;Related Lymphedema\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePhA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePhase Angle\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBody Mass Index\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eECW\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eExtracellular Water\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTBW\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTotal Body Water\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBIA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBioelectrical Impedance Analysis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eROC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eReceiver Operating Characteristic\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAUC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eArea Under the Curve\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eStandard Deviation\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTVM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTape Circumference Measurement\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in accordance with the guidelines of the Declaration of Helsinki. Ethical approval was granted by the Ethics Review Committee of the Sanhuan Cancer Hospital in Chaoyang District, Beijing (SH-2023036).\u003c/p\u003e\n\u003cp\u003eAll participants provided informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in this study are included in the article/supplementary material, and further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they received financial support for this research and publication of the article. This study was supported by the National Natural Science Foundation of China (No. 82372585).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJF: Data curation, Investigation, Writing, review, and editing. YQ: Formal analysis, writing the original draft, writing the review, and editing.YL:Data curation, Investigation.YZ:Data curation, Investigation.DS:Data curation, Investigation.XZ:Data curation, Investigation.MH:Data curation, Investigation.SS:Data curation, Investigation.\u003c/p\u003e\n\u003cp\u003eMH: Data curation, Formal analysis, Investigation, Supervision, Writing, review and editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSun, Y.-S., et al., \u003cem\u003eRisk Factors and Preventions of Breast Cancer.\u003c/em\u003e International Journal of Biological Sciences, 2017. \u003cstrong\u003e13\u003c/strong\u003e(11): p. 1387-1397.\u003c/li\u003e\n\u003cli\u003eMarotta, N., et al., \u003cem\u003eEfficacy of kinesio taping on upper limb volume reduction in patients with breast cancer-related lymphedema: a systematic review of randomized controlled trials.\u003c/em\u003e Eur J Phys Rehabil Med, 2023. \u003cstrong\u003e59\u003c/strong\u003e(2): p. 237-247.\u003c/li\u003e\n\u003cli\u003eDeSantis, C.E., et al., \u003cem\u003eBreast cancer statistics, 2015: Convergence of incidence rates between black and white women.\u003c/em\u003e CA Cancer J Clin, 2016. \u003cstrong\u003e66\u003c/strong\u003e(1): p. 31-42.\u003c/li\u003e\n\u003cli\u003eAhn, H.R., et al., \u003cem\u003eIncidence and risk factors of breast cancer-related lymphedema in Korea: a nationwide retrospective cohort study.\u003c/em\u003e Int J Surg, 2024. \u003cstrong\u003e110\u003c/strong\u003e(6): p. 3518-3526.\u003c/li\u003e\n\u003cli\u003eClark, B., J. Sitzia, and W. Harlow, \u003cem\u003eIncidence and risk of arm oedema following treatment for breast cancer: a three-year follow-up study.\u003c/em\u003e QJM, 2005. \u003cstrong\u003e98\u003c/strong\u003e(5): p. 343-8.\u003c/li\u003e\n\u003cli\u003eKonishi, T., et al., \u003cem\u003eRisk factors for arm lymphedema following breast cancer surgery: a Japanese nationwide database study of 84,022 patients.\u003c/em\u003e Breast Cancer, 2023. \u003cstrong\u003e30\u003c/strong\u003e(1): p. 36-45.\u003c/li\u003e\n\u003cli\u003eSarri, A.J., et al., \u003cem\u003eLymphoscintigraphy detecting alterations of upper limb lymphatic flow following early sentinel lymph node biopsy in breast cancer.\u003c/em\u003e Breast Cancer (Dove Med Press), 2017. \u003cstrong\u003e9\u003c/strong\u003e: p. 279-285.\u003c/li\u003e\n\u003cli\u003eBates, D.O., \u003cem\u003eAn interstitial hypothesis for breast cancer related lymphoedema.\u003c/em\u003e Pathophysiology, 2010. \u003cstrong\u003e17\u003c/strong\u003e(4): p. 289-94.\u003c/li\u003e\n\u003cli\u003eShinde, S.B., et al., \u003cem\u003eEstimation of Hand Function Impairment in Breast Cancer Survivors with Lymphedema.\u003c/em\u003e South Asian J Cancer, 2025. \u003cstrong\u003e14\u003c/strong\u003e(1): p. 23-29.\u003c/li\u003e\n\u003cli\u003eKim, W.J., et al., \u003cem\u003eFeasibility of segmental bioelectrical impedance analysis for mild- to moderate-degree breast cancer-related lymphedema: Correlation with circumferential volume measurement and phase angle.\u003c/em\u003e Medicine (Baltimore), 2021. \u003cstrong\u003e100\u003c/strong\u003e(4): p. e23722.\u003c/li\u003e\n\u003cli\u003eAldrich, M.B., et al., \u003cem\u003eLymphatic abnormalities in the normal contralateral arms of subjects with breast cancer-related lymphedema as assessed by near-infrared fluorescent imaging.\u003c/em\u003e Biomed Opt Express, 2012. \u003cstrong\u003e3\u003c/strong\u003e(6): p. 1256-65.\u003c/li\u003e\n\u003cli\u003eModi, S., et al., \u003cem\u003eHuman lymphatic pumping measured in healthy and lymphoedematous arms by lymphatic congestion lymphoscintigraphy.\u003c/em\u003e J Physiol, 2007. \u003cstrong\u003e583\u003c/strong\u003e(Pt 1): p. 271-85.\u003c/li\u003e\n\u003cli\u003eLi, N., et al., \u003cem\u003eAn arabinogalactan isolated from Cynanchum atratum promotes lymphangiogenesis and lymphatic vessel remodeling to alleviate secondary lymphedema.\u003c/em\u003e Int J Biol Macromol, 2024. \u003cstrong\u003e273\u003c/strong\u003e(Pt 2): p. 133061.\u003c/li\u003e\n\u003cli\u003eNorman, K., et al., \u003cem\u003eBioelectrical phase angle and impedance vector analysis--clinical relevance and applicability of impedance parameters.\u003c/em\u003e Clin Nutr, 2012. \u003cstrong\u003e31\u003c/strong\u003e(6): p. 854-61.\u003c/li\u003e\n\u003cli\u003eNorman, K., et al., \u003cem\u003eCutoff percentiles of bioelectrical phase angle predict functionality, quality of life, and mortality in patients with cancer.\u003c/em\u003e Am J Clin Nutr, 2010. \u003cstrong\u003e92\u003c/strong\u003e(3): p. 612-9.\u003c/li\u003e\n\u003cli\u003eClarkson, P.M. and S.A. Kaufman, \u003cem\u003eShould resistance exercise be recommended during breast cancer treatment?\u003c/em\u003e Med Hypotheses, 2010. \u003cstrong\u003e75\u003c/strong\u003e(2): p. 192-5.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 3","content":"\u003cp\u003eTable 3 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"lymphedema, risk factors, breast cancer, ultrasound, phase angle","lastPublishedDoi":"10.21203/rs.3.rs-7414488/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7414488/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eBreast cancer-related lymphoma (BCRL) develops in 25% of breast cancer patients following treatment. It is a chronic condition where swelling persists despite interventions like compression hosiery and manual lymphatic drainage.\u003c/p\u003e\u003ch2\u003eAim\u003c/h2\u003e\u003cp\u003eThis study aimed to determine factors associated with early-stage lymphedema in women with breast cancer, investigate the relationship between lymphedema, lymphatic flow velocity, and body composition, and explore potential mechanisms for preventing BCRL.\u003c/p\u003e\u003ch2\u003eDesign:\u003c/h2\u003e\u003cp\u003eCross-sectional study.\u003c/p\u003e\u003ch2\u003eSetting:\u003c/h2\u003e\u003cp\u003eInpatient rehabilitation unit\u003c/p\u003e\u003ch2\u003ePopulation:\u003c/h2\u003e\u003cp\u003eThirty-four female patients with confirmed BCRL (age: 49.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7 years; height: 158.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1 cm; weight: 60.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8 kg) and 26 healthy controls (age: 50.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1 years; height: 160.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9 cm; weight: 62.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1 kg) were enrolled between 2024 and 2025.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eLymphatic duct diameter and flow velocity at the right venous angle were measured using ultrasound. Hand grip strength was assessed using a dynamometer, and body composition was analyzed using a bioimpedance analyzer (InBody 770; InBody Co., Seoul, Korea). Statistical analyses included paired t-tests to compare BCRL and control groups and Spearman's correlation for associations between clinical characteristics. Receiver operating characteristic analysis was used to determine diagnostic thresholds for BCRL.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eCompared to healthy controls, the BCRL group showed significantly higher lymphatic flow velocity, lower phase angle, and reduced grip strength (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Age was positively correlated with extracellular water (ECW) but negatively with phase angle, while grip strength was positively correlated with phase angle. The optimal diagnostic cutoffs for lymphedema were: lymphatic flow velocity\u0026thinsp;\u0026ge;\u0026thinsp;7.7 cm/s (35.3% sensitivity, 96.2% specificity), phase angle\u0026thinsp;\u0026le;\u0026thinsp;4.05\u0026deg; (92.3% sensitivity, 70.6% specificity), and grip strength\u0026thinsp;\u0026le;\u0026thinsp;18.1 N (88.5% sensitivity, 67.6% specificity).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIncreased lymphatic flow velocity, decreased phase angle, and reduced grip strength were significant early-stage indicators of BCRL.\u003c/p\u003e\u003ch2\u003eClinical rehabilitation impact:\u003c/h2\u003e\u003cp\u003eIdentifying early risk factors for lymphedema can help clinicians understand its mechanism and enable timely interventions to prevent its progression.\u003c/p\u003e","manuscriptTitle":"Screening for Breast Cancer-Related Lymphedema: A Cross-Sectional Study Using Ultrasound and Bioelectrical Impedance Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-24 05:13:12","doi":"10.21203/rs.3.rs-7414488/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2025-09-15T14:07:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-21T16:43:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-21T00:34:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-21T00:34:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2025-08-20T07:11:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a306c39a-5e13-4b23-8023-5ae1fd467c0c","owner":[],"postedDate":"September 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-24T05:13:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-24 05:13:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7414488","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7414488","identity":"rs-7414488","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}