Lymphedema Risk In Patients Research Articles

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of developing cancer-related lymphedema following axillary lymph node dissection (ALND).

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.

Development and Validation of Upper Limb Lymphedema in Patients After Breast Cancer Surgery Using a Practicable Machine Learning Model: A Retrospective Cohort Study.

Upper 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. We 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). Of 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. The 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.

Evaluating Operative Times for Intraoperative Conversion of Axillary Node Biopsy to Axillary Lymph Node Dissection with Immediate Lymphatic Reconstruction.

Lymphedema can occur in patients undergoing axillary lymph node dissection (ALND) and radiation for breast cancer. Immediate lymphatic reconstruction (ILR) is performed to decrease the risk of lymphedema in patients after ALND. Some patients who ultimately require ALND are candidates for attempted sentinel lymph node biopsy (SLNB) or targeted axillary excision. In those scenarios, ALND can be performed (1) immediately if frozen sections are positive or (2) as a second operation following permanent pathology. The purpose of this study is to evaluate immediate ALND/ILR following positive intraoperative frozen sections to guide surgical decision-making and operative planning. A single-center retrospective review was performed (2019-2022) for breast cancer patients undergoing axillary node surgery with breast reconstruction. Patients were divided into two groups: immediate conversion to ALND/ILR (Group 1) and no immediate conversion to ALND (Group 2). Demographic data and operative time were recorded. There were 148 patients who underwent mastectomy, tissue expander (TE) reconstruction, and axillary node surgery. Group 1 included 30 patients who had mastectomy, sentinel node/targeted node biopsy, TE reconstruction, and intraoperative conversion to immediate ALND/ILR. Group 2 had 118 patients who underwent mastectomy with TE reconstruction and SLNB with no ALND or ILR. Operative time for bilateral surgery was 303.1 ± 63.2 minutes in Group 1 compared with 222.6 ± 52.2 minutes in Group 2 (p = 0.001). Operative time in Group 1 patients undergoing unilateral surgery was 252.3 ± 71.6 minutes compared with 171.3 ± 43.2 minutes in Group 2 (p = 0.001). Intraoperative frozen section of sentinel/targeted nodes extended operative time by approximately 80 minutes in patients undergoing mastectomy with breast reconstruction and conversion of SLNB to ALND/ILR. Intraoperative conversion to ALND adds unpredictability to the operation as well as additional potentially unaccounted operative time. However, staging ALND requires an additional operation.

Quantifying radiation in the axillary bed at the site of lymphedema surgical prevention.

Immediate lymphatic reconstruction (ILR) is a procedure known to reduce the risk of lymphedema in patients undergoing axillary lymph node dissection (ALND). However, patients who receive adjuvant radiotherapy are at increased risk of lymphedema. The aim of this study was to quantify the extent of radiation at the site of surgical prevention. We recently began deploying clips at the site of ILR to identify the site during radiation planning. A retrospective review was performed to identify breast cancer patients who underwent ILR with clip deployment and adjuvant radiation therapy from October 2020 to April 2022. Patients were excluded if they had not completed radiotherapy. The exposure and dose of radiation received by the site was determined and recorded. In a cohort of 11 patients, the site fell within the radiation field in 7 patients (64%) and received a median dose of 4280cGy. Among these 7 patients, 3 had sites located within tissue considered at risk of oncologic recurrence and the remaining 4 sites received radiation from a tangential field treating the breast or chest wall. The median dose to the ILR site for the 4 patients whose sites were outside the radiation fields was 233cGy. Our findings suggest that even when the site of surgical prevention was not within the targeted radiation field during treatment planning, it remains susceptible to radiation. Strategies for limiting radiation at this site are needed.

Risk of Lymphedema and Death after Lymph Node Dissection with Neoadjuvant and Adjuvant Treatments in Patients with Breast Cancer: An Eight-Year Nationwide Cohort Study.

Knowledge on the impact of neoadjuvant and adjuvant treatments on post-surgery lymphedema (LE) in patients with breast cancer is limited due to methodological limitations and an insufficient sample size. We investigated the risk of LE in patients going through long-term anticancer treatment regimens using a national cohort from the Korean National Health Insurance Service database from 2011-2013. Incidence rate ratio, Kaplan-Meier analysis, and Cox proportional regression analysis were performed. A total of 39,791 patients were included. While minimal lymph node dissection (SLNB) reduced the risk of LE (hazard ratio [HR] 0.51) as expected, neoadjuvant chemotherapy (NAC) followed by SLNB did not reduce the risk. Adjusting for adjuvant chemotherapy (AC) as time-varying exposure decreased the risk of LE in the SLNB group (HR 0.51), but not the mortality risk (HR 0.861). A longer duration of NAC, especially taxane-based, combined with SLNB reversed the effect and increased risk of LE. The findings highlight the importance of not only early surveillance before and after surgery, but also long-term surveillance during adjuvant treatment by surgeons and oncologists in order to reduce the risk of LE.

Abstract P5-08-09: Does Breast Inflammation Contribute to Lymphedema Risk in Patients Treated with Axillary Lymph Node Dissection?

Abstract 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 &amp;lt; 0.001). Overall, 54% had CLS-B, with severe inflammation (&amp;gt; 0.4 CLS-B/cm2) identified in 71 (25%) patients. CLS-B presence correlated with BMI (36% [BMI &amp;lt; 25], 63% [BMI 25-30], 70% [BMI &amp;gt; 30], p &amp;lt; 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.

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

<h3>Purpose/Objective(s)</h3> To study the relationship between the axillary-lateral thoracic vessel juncture (ALTJ) dose and lymphedema risk in women with breast cancer in the context of other known risk factors. <h3>Materials/Methods</h3> A total of 1,488 women with breast cancer, from two institutions, treated with multimodal therapies were analyzed. ALTJ was delineated, and dose-volume histogram (DVH) parameters (maximum dose [D_max], D_mean, D_min, volume receiving 5 Gy [V_5Gy], V_10Gy, V_15Gy, V_20Gy, V_25Gy, V_30Gy, V_35Gy, V_40Gy, V_45Gy, and V_50Gy) were assessed. Doses were converted to the equivalent dose of 2 Gy using a linear-quadratic model (<i>α</i>/<i>β</i> = 3). <h3>Results</h3> The cumulative incidence of lymphedema development was 6.8% at 5-years. Lymphedema risk increased for each 10-Gy increment in the ALTJ D_mean (adjusted hazard ratio 1.2, 95% confidence interval (CI) 1.1–1.4). The random survival forest model better predicted lymphedema risk when ALTJ DVH parameters were integrated into the model with a c-index of 0.91 (<i>p</i> < 0.001). Surgical extent followed by ALTJ D_mean were the most significant indicators of lymphedema risk. In the decision tree model developed with a hierarchical classification and regression tree, the 5-year lymphedema risk was significantly elevated in patients with an ALTJ D_mean >35 Gy (12.8% vs. 1.0%, <i>p</i> < 0.001) among patients who had ≤6 sampled lymph nodes. <h3>Conclusion</h3> A mean dose ≤35 Gy to the ALTJ is a suggested dose constraint for preventing lymphedema in patients who undergo less extensive axillary surgery. Although further validation is required, our dose constraints can be incorporated into future prospective protocols to investigate the impact of axillary treatment.

Paclitaxel versus docetaxel-based neoadjuvant chemotherapy and risk of lymphedema in breast cancer patients.

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 &gt;2.0-cm increase in arm circumference, or &gt;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&lt;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&lt;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.

Repurposing the Mammographic Breast Density Category for Predicting Lymphedema Risk in Patients With Breast Cancer

Repurposing the Mammographic Breast Density Category for Predicting Lymphedema Risk in Patients With Breast Cancer

Lower extremity lymphatic function predicted by body mass index: a lymphoscintigraphic study of obesity and lipedema.

Patients with obesity and lipedema commonly are misdiagnosed as having lymphedema. The conditions share phenotypic overlap and can influence each other. The purpose of this study was to delineate obesity-induced lymphedema, obesity without lymphedema, and lipedema in order to improve their diagnosis and treatment. Our Lymphedema Center database of 700 patients was searched for patients with obesity-induced lymphedema (OIL), obesity without lymphedema (OWL), and lipedema. Patient age, sex, diagnosis, cellulitis history, body mass index (BMI), and treatment were recorded. Only subjects with lymphoscintigraphic documentation of their lymphatic function were included. Ninety-eight patients met inclusion criteria. Subjects with abnormal lymphatic function (n = 46) had a greater BMI (65 ± 12) and cellulitis history (n = 30, 65%) compared to individuals with normal lymphatic function [(BMI 42 ± 10); (cellulitis n = 8, 15%)] (p < 0.001). Seventeen patients had a history of lipedema and two exhibited abnormal lymphatic function (BMI 45, 54). The risk of having lower extremity lymphedema was predicted by BMI: BMI < 40 (0%), 40-49 (17%), 50-59 (63%), 60-69 (86%), 70-79 (91%), ≥80 (100%). Five patients with OIL (11%) underwent resection of massive localized lymphedema (MLL) or suction-assisted lipectomy. Three individuals (18%) with lipedema were treated with suction-assisted lipectomy. The risk of lymphedema in patients with obesity and lipedema can be predicted by BMI; confirmation requires lymphoscintigraphy. Individuals with OIL are at risk for cellulitis and MLL. Patients with a BMI > 40 are first managed with weight loss. Excisional procedures can further reduce extremity size once BMI has been lowered.

Immediate Lymphatic Reconstruction after Axillary Lymphadenectomy: A Single-Institution Early Experience.

Lymphedema is progressive arm swelling from lymphatic dysfunction which can occur in 30% patients undergoing axillary dissection/radiation for breast cancer. Immediate lymphatic reconstruction (ILR) is performed in an attempt decrease the risk of lymphedema in patients undergoing axillary lymph node dissection (ALND). The purpose of this study was to assess the efficacy of ILR in preventing lymphedema rates in ALND patients. An institutional review board-approved retrospective review was performed of all patients who underwent ILR from 2017 to 2019. Patient demographics, comorbidities, operative and pathologic findings, number of LVAs, limb measurements, complications, and follow-up were recorded and analyzed. Student's sample t-test, Fisher's exact test, and ANOVA were used to analyze data; significance was set at p < 0.05. Thirty-three patients were included in this analysis. Three patients (9.1%) developed persistent lymphedema, and two patients (6.1%) developed transient arm edema that resolved with compression and massage therapy. A significant effect was found for body mass index and the number of lymph nodes taken on the development of lymphedema (p < 0.01). The rate of lymphedema in this series was 9.1%, which is an improvement from historical rates of lymphedema. Our findings support ILR as a technique that potentially decreases the incidence of lymphedema after axillary lymphadenectomy. Obesity and number of lymph nodes removed were significant predictive variables for the development of lymphedema following LVA.

An Investigational Surgical Procedure (Vascularized Lymph Node Transfer) in Reducing the Risk of Lymphedema in Patients With Breast Cancer Undergoing Breast Reconstruction

An Investigational Surgical Procedure (Vascularized Lymph Node Transfer) in Reducing the Risk of Lymphedema in Patients With Breast Cancer Undergoing Breast Reconstruction

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

Sentinel lymph node biopsy (SLNB) is an indispensable surgical procedure in staging and management of intermediate-to-thick melanomas. Although recent studies have demonstrated that complete lymph node dissection (CLND) does not improve 3-year specific survival, its utility in increasing the disease-free period and the control of local disease remains confirmed. The most frequent complication related to CLND is lymphedema, which may affect up to 20% of patients undergoing CLND. The preventive use of lymphatic-venous micro-anastomoses could avoid this complication. We performed a single-institution retrospective case-control study. CLND was proposed to all subjects with positive-SLNB; a preventive procedure involving multiple lymphaticovenular anastomoses (PMA) was performed in a cohort of subjects undergoing CLND. Frequency of lymphedema was compared among subjects undergoing and not-undergoing PMA during CLND. We selected patients affected by melanoma of the trunk and with a minimum follow-up of 3 years, identifying 23 patients who underwent PMA during CLND (PMA group) and 120 subjects who underwent CLND without PMA (control group). The frequency of lymphedema was significantly lower in the PMA group than in the control group (4.3% vs. 24.2%, p = 0.03). Patients of the PMA group and the control group showed similar 3-year recurrence-free period (65.2% vs. 62.5%, log-rank test p = 0.88) and 3-year overall survival (73.9% vs. 72.5%, log-rank test p = 0.97) and frequency of nonsentinel-nodemetastases (26.7% vs. 30.4%, p = 0.71). PMA appear to represent a useful and safe procedure in reducing the risk of lymphedema in patients with melanoma undergoing CLND.

A Lymphedema Surveillance Program for Breast Cancer Patients Reveals the Promise of Surgical Prevention

BackgroundBreast cancer–related lymphedema (BCRL) is one of the most significant survivorship issues in breast cancer management. Presently, there is no cure for BCRL. The single greatest risk factor for developing BCRL is an axillary lymph node dissection (ALND). Lymphatic Microsurgical Preventative Healing Approach (LYMPHA) is a surgical procedure to reduce the risk of lymphedema in patients undergoing an ALND. We present our single institution results after offering LYMPHA in the context of an established lymphedema surveillance program. Materials and methodsA retrospective review of our lymphedema surveillance program at the University of Florida was performed over a 2-year period (March 2014-March 2016). LYMPHA was offered to patients undergoing ALND beginning in March 2015. Patients who developed lymphedema were compared with those who did not. Demographics and potential risk factors for development of lymphedema such as age, body mass index, clinical stage, radiotherapy, and chemotherapy were reviewed. ResultsEighty-seven patients participated in the surveillance program over the study period with an average age of 60 y (range 32-83) and body mass index of 30 kg/m2 (range 17-46). The single most significant risk factor for the development for lymphedema was an ALND (P < 0.001). One of 67 patients undergoing a sentinel lymph node biopsy developed lymphedema (1.5%). Four of 10 patients who underwent an ALND alone developed lymphedema (40%). One of 8 patients in the ALND + LYMPHA group developed transient lymphedema (12.5%). ConclusionsOffering LYMPHA with ALND decreased our institutional rate of lymphedema from 40% to 12.5%. Long-term follow-up and randomized control trials are necessary to further elucidate the promise of this surgical technique to reduce the incidence of BCRL.

Risk of lymphedema after mastectomy: potential benefit of applying ACOSOG Z0011 protocol to mastectomy patients

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.

Impact of body mass index and weight fluctuation on lymphedema risk in patients treated for breast cancer

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.

Residual Lymph Node Disease After Neoadjuvant Chemotherapy Predicts an Increased Risk of Lymphedema in Node-Positive Breast Cancer Patients

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.