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Purpose/Objective Lymphedema following breast cancer treatment can be an irreversible condition with a negative impact on quality of life. The goal of this study was to identify radiotherapy-related risk factors for lymphedema. Methods and Materials From 2005–2012, we prospectively performed arm volume measurements on 1,476 breast cancer patients at our institution using a Perometer. Treating each breast individually, 1099/1501 (73%) received radiotherapy. Arm measurements were performed pre- and post-operatively. Lymphedema was defined as ≥10% arm volume increase occurring >3 months post-operative. Univariate and multivariate Cox proportional hazard models were used to evaluate risk factors for lymphedema. Results At a median follow-up of 25.4 months (range 3.4–82.6), the 2-year cumulative incidence of lymphedema was 6.8%. Cumulative incidence by radiotherapy type was: 3.0% (no radiotherapy), 3.1% (breast or chest wall alone), 21.9% (supraclavicular (SC)), and 21.1% (SC and posterior axillary boost (PAB)). On multivariate analysis, the hazard ratio for RLNR (SC±PAB) was 1.7 (p = 0.025) compared to breast/chest wall radiation alone. There was no difference in lymphedema risk between SC and SC+PAB (p=0.96). Other independent risk factors included early post-operative swelling (p <0.0001), higher BMI (p<0.0001), greater number of lymph nodes dissected (p =0.018), and axillary lymph node dissection (p=0.0001). Conclusions In a large cohort of breast cancer patients prospectively screened for lymphedema, RLNR significantly increased risk of lymphedema compared to breast/chest wall radiation alone. When considering use of RLNR, clinicians should weigh the potential benefit of RLNR for control of disease with the increased risk of lymphedema.

Purpose-The lack of standard method to quantify developing breast cancer related lymphedema (BCRL) impedes the progress in research and clinical practice. We therefore developed a simple and practical formula for quantifying both the asymmetry of upper extremities' volumes and their temporal changes.Methods & Materials-We present the analysis of bilateral perometer measurements of the upper extremity in a series of 677 women who prospectively underwent lymphedema screening during their treatment for unilateral breast cancer at Massachusetts General Hospital between August 2005 and November 2008. Four sources of variation are analyzed: between repeated measurements on the same arm at the same session, between both arms at the baseline (preoperative) visit, in follow-up measurements, and between patients. We analyze the effects of hand dominance, time since diagnosis and surgery, age, weight, and body mass index (BMI).Results-The statistical distribution of variation of measurements suggests that the ratio of volume ratios is most appropriate for quantification of both asymmetry and temporal changes. Therefore, we present the formula for Relative Volume Change (RVC): RVC=(A 2 U 1 )/(U 2 A 1 )-1, where A 1 , A 2 are arm volumes on the side of the treated breast at two different time points, and U 1 , U 2 are volumes on the contralateral side. RVC is not significantly associated with hand dominance, age, or time since diagnosis. Baseline weight correlates (P=0.0016) with higher RVC; however, baseline BMI or weight changes over time do not. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-We propose the use of RVC formula to assess the presence and the course of BCRL in clinical practice and research. Conflicts of Interest

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