Impact of Ipsilateral Blood Draws, Injections, Blood Pressure Measurements, and Air Travel on the Risk of Lymphedema for Patients Treated for Breast Cancer.

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.

Immediate Implant Reconstruction Is Associated With a Reduced Risk of Lymphedema Compared to Mastectomy Alone: A Prospective Cohort Study.

OBJECTIVE: We sought to determine the risk of lymphedema associated with immediate breast reconstruction compared to mastectomy alone. BACKGROUND: Immediate breast reconstruction is increasingly performed at the time of mastectomy. Few studies have examined whether breast reconstruction impacts development of lymphedema. METHODS: A total of 616 patients with breast cancer who underwent 891 mastectomies between 2005 and 2013 were prospectively screened for lymphedema at our institution, with 22.2 months' median follow-up. Mastectomies were categorized as immediate implant, immediate autologous, or no reconstruction. Arm measurements were performed preoperatively and during postoperative follow-up using a Perometer. Lymphedema was defined as 10% or more arm volume increase compared to preoperative. Kaplan-Meier and Cox regression analyses were performed to determine lymphedema rates and risk factors. RESULTS: Of 891 mastectomies, 65% (580/891) had immediate implant, 11% (101/891) immediate autologous, and 24% (210/891) no reconstruction. The two-year cumulative incidence of lymphedema was as follows: 4.08% [95% confidence interval (CI): 2.59-6.41%] implant, 9.89% (95% CI: 4.98-19.1%) autologous, and 26.7% (95% CI: 20.4-34.4%) no reconstruction. By multivariate analysis, immediate implant [hazards ratio (HR): 0.352, P < 0.0001] but not autologous (HR: 0.706, P = 0.2151) reconstruction was associated with a significantly reduced risk of lymphedema compared to no reconstruction. Axillary lymph node dissection (P < 0.0001), higher body mass index (P < 0.0001), and greater number of nodes dissected (P = 0.0324) were associated with increased lymphedema risk. CONCLUSIONS: This prospective study suggests that in patients for whom implant-based reconstruction is available, immediate implant reconstruction does not increase the risk of lymphedema compared to mastectomy alone.

Impact of adjuvant taxane-based chemotherapy on development of breast cancer-related lymphedema: results from a large prospective cohort.

Taxane-based chemotherapy for the treatment of breast cancer is associated with fluid retention in the extremities; however, its association with development of breast cancer-related lymphedema is unclear. We sought to determine if adjuvant taxane-based chemotherapy increased risk of lymphedema or mild swelling of the upper extremity. 1121 patients with unilateral breast cancer were prospectively screened for lymphedema with perometer measurements. Lymphedema was defined as a relative volume change (RVC) of ≥10 % from preoperative baseline. Mild swelling was defined as RVC 5- <10 %. Clinicopathologic characteristics were obtained via medical record review. Kaplan-Meier and Cox proportional hazard analyses were performed to determine lymphedema rates and risk factors. 29 % (324/1121) of patients were treated with adjuvant taxane-based chemotherapy. The 2-year cumulative incidence of lymphedema in the overall cohort was 5.27 %. By multivariate analysis, axillary lymph node dissection (ALND) (p < 0.0001), higher body mass index (p = 0.0007), and older age at surgery (p = 0.04) were significantly associated with increased risk of lymphedema; however, taxane chemotherapy was not significant when compared to no chemotherapy and non-taxane chemotherapy (HR 1.14, p = 0.62; HR 1.56, p = 0.40, respectively). Chemotherapy with docetaxel was significantly associated with mild swelling on multivariate analysis in comparison to both no chemotherapy and non-taxane chemotherapy groups (HR 1.63, p = 0.0098; HR 2.15, p = 0.02, respectively). Patients who receive taxane-based chemotherapy are not at an increased risk of lymphedema compared to patients receiving no chemotherapy or non-taxane adjuvant chemotherapy. Those treated with docetaxel may experience mild swelling, but this does not translate into subsequent lymphedema.

Radiation therapy risk factors for development of lymphedema in patients treated with regional lymph node irradiation for breast cancer.

PURPOSE: We previously evaluated the risk of breast cancer-related lymphedema (LE) with the addition of regional lymph node irradiation (RLNR) and found an increased risk when RLNR is used. Here we analyze the association of technical radiation therapy (RT) factors in RLNR patients with the risk of LE development. METHODS AND MATERIALS: From 2005 to 2012, we prospectively screened 1476 women for LE who underwent surgery for breast cancer. Among 1507 breasts treated, 172 received RLNR and had complete technical data for analysis. RLNR was delivered as supraclavicular (SC) irradiation (69% [118 of 172 patients]) or SC plus posterior axillary boost (PAB) (31% [54 of 172]). Bilateral arm volume measurements were performed pre- and postoperatively. Patients' RT plans were analyzed for SC field lateral border (relative to the humeral head), total dose to SC, RT fraction size, beam energy, and type of tangent (normal vs wide). Cox proportional hazards models were used to analyze associated risk factors for LE. RESULTS: Median postoperative follow-up was 29.3 months (range: 4.9-74.1 months). The 2-year cumulative incidence of LE was 22% (95% confidence interval [CI]: 15%-32%) for SC and 20% (95% CI: 11%-37%) for SC plus PAB (SC+PAB). None of the analyzed variables was significantly associated with LE risk (extent of humeral head: P=.74 for <1/3 vs >2/3, P=.41 for 1/3 to 2/3 vs >2/3; P=.40 for fraction size of 1.8 Gy vs 2.0 Gy; P=.57 for beam energy 6 MV vs 10 MV; P=.74 for tangent type wide vs regular; P=.66 for SC vs SC+PAB). Only pretreatment body mass index (hazard ratio [HR]: 1.09; 95% CI: 1.04-1.15, P=.0007) and the use of axillary lymph node dissection (HR: 7.08, 95% CI: 0.98-51.40, P=.05) were associated with risk of subsequent LE development. CONCLUSIONS: Of the RT parameters tested, none was associated with an increased risk of LE development. This study underscores the need for future work investigating alternative RLNR risk factors for LE.

The impact of breast cancer-related lymphedema on the ability to perform upper extremity activities of daily living.

We sought to assess the association of breast cancer-related lymphedema (BCRL) with the ability to perform upper extremity activities of daily living (ADL) in our patient population. 324 breast cancer patients who had received treatment for unilateral breast cancer at our institution between 2005 and 2014 were prospectively screened for lymphedema. Bilateral arm measurements were performed pre-operatively and during post-operative follow-up using a Perometer. Patients completed an extensive quality of life (QOL) questionnaire at the time of each study assessment. Lymphedema was defined as a relative volume change (RVC) of ≥10% from the patient's pre-operative baseline measurement. Linear regression models were used to evaluate the relationship between post-operative arm function score (as a continuous variable) and RVC, demographic, clinical, and QOL factors. By multivariate analysis, greater fear of lymphedema (p < 0.0001), more pain (p < 0.0001), body mass index >25 (p = 0.0015), mastectomy (p = 0.0001), and having an axillary node dissection (p = 0.0045) were all associated with lower functional scores. Higher emotional well-being score (p < 0.0001) and adjuvant chemotherapy (p = 0.0005) were associated with higher post-operative functional score. Neither low-level volume changes (5-10 % RVC) nor BCRL (RVC ≥10 %) were associated with ability to perform upper extremity ADL as measured by self-report (p = 0.99, p = 0.79). This prospective study demonstrates that low-level changes in arm volume (RVC 5-10 %) as well as clinically significant BCRL (RVC ≥10 %) did not impact the self-reported ability to use the affected extremity for ADL. These findings may help to inform clinicians and patients on the importance of prospective screening for lymphedema and QOL which enables early detection and intervention.

Lymphedema following breast cancer treatment and impact on quality of life: a review.

Lymphedema resulting from breast cancer treatment is a chronic condition which can significantly compromise quality of life. We sought to review various aspects of breast-cancer related lymphedema including measurement techniques, definitions, risk factors, and specifically, impact on physical, psychological, and emotional well-being of women treated for breast cancer. For the purpose of this review, we performed a literature search using PubMed for articles on lymphedema secondary to breast cancer treatment published since 1997. While improvements in breast cancer therapy have contributed to a decrease in the incidence of lymphedema, the overall negative impact the condition has on patients and survivors has remained unchanged. The development of lymphedema results in physical impairments including compromised function, diminished strength, fatigue, and pain in the affected arm. Affected women may have decreased self-confidence resulting from a distorted body image. Negative emotions reported by women with lymphedema include anxiety, frustration, sadness, anger, fear, and increased self-consciousness. Lymphedema secondary to breast cancer treatment remains a significant quality of life issue, with known consequences related to a woman's physical, psychological, and emotional well-being.

Factors associated with fear of lymphedema after treatment for breast cancer.

PURPOSE/OBJECTIVES: To identify demographic and treatment characteristics associated with postoperative fear of lymphedema. DESIGN: Prospective cohort study. SETTING: Outpatient breast clinic at a comprehensive cancer center in the northeastern United States. SAMPLE: 324 patients undergoing treatment for unilateral breast cancer. METHODS: Women with breast cancer were prospectively screened for lymphedema (relative volume change of 10% or greater) preoperatively and every three to eight months postoperatively via Perometer arm volume measurements. Fear was simultaneously evaluated via questionnaire. Multivariate linear mixed-effects regression models were used to identify factors associated with mean postoperative fear score and to plot the average fear score over time within axillary surgery type subgroups. MAIN RESEARCH VARIABLES: Postoperative fear of lymphedema. FINDINGS: Higher preoperative fear score (p < 0.0001), younger age at diagnosis (p = 0.0038), and axillary lymph node dissection (ALND) (p < 0.0001) were significantly associated with higher mean postoperative fear score. The average fear score changed nonlinearly over time (p < 0.0001), decreasing from preoperative to 24 months postoperative and leveling thereafter. CONCLUSIONS: Preoperative fear, younger age at diagnosis, and ALND may contribute to postoperative fear of lymphedema. IMPLICATIONS FOR NURSING: Individualized education that begins preoperatively, continues throughout treatment, and is re-emphasized 24 months postoperatively may help minimize fear of lymphedema.

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.

The impact of radiation therapy on the risk of lymphedema after treatment for breast cancer: a prospective cohort study.

PURPOSE/OBJECTIVE: Lymphedema after breast cancer treatment can be an irreversible condition with a negative impact on quality of life. The goal of this study was to identify radiation therapy-related risk factors for lymphedema. METHODS AND MATERIALS: From 2005 to 2012, we prospectively performed arm volume measurements on 1476 breast cancer patients at our institution using a Perometer. Treating each breast individually, 1099 of 1501 patients (73%) received radiation therapy. Arm measurements were performed preoperatively and postoperatively. Lymphedema was defined as ≥10% arm volume increase occurring >3 months postoperatively. Univariate and multivariate Cox proportional hazard models were used to evaluate risk factors for lymphedema. RESULTS: At a median follow-up time of 25.4 months (range, 3.4-82.6 months), the 2-year cumulative incidence of lymphedema was 6.8%. Cumulative incidence by radiation therapy type was as follows: 3.0% no radiation therapy, 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 regional lymph node radiation (RLNR) (SC ± PAB) was 1.7 (P=.025) compared with breast/chest wall radiation alone. There was no difference in lymphedema risk between SC and SC + PAB (P=.96). Other independent risk factors included early postoperative swelling (P<.0001), higher body mass index (P<.0001), greater number of lymph nodes dissected (P=.018), and axillary lymph node dissection (P=.0001). CONCLUSIONS: In a large cohort of breast cancer patients prospectively screened for lymphedema, RLNR significantly increased the risk of lymphedema compared with breast/chest wall radiation alone. When considering use of RLNR, clinicians should weigh the potential benefit of RLNR for control of disease against the increased risk of lymphedema.

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.

Defining a threshold for intervention in breast cancer-related lymphedema: what level of arm volume increase predicts progression?

The purpose of this study is to evaluate arm volume measurements and clinico-pathologic characteristics of breast cancer patients to define a threshold for intervention in breast cancer-related lymphedema. We prospectively performed arm volume measurements on breast cancer patients using a Perometer. Arm measurements were performed pre- and post-operatively, and change in arm volume was quantified using a relative volume change (RVC) equation. Patient and treatment risk factors were evaluated. Cox proportional hazards models with time-dependent covariates for RVC were used to evaluate whether RVC elevations of ≥3 to <5 % or ≥5 to <10 % occurring ≤3 months or >3 months after surgery were associated with progression to ≥10 % RVC. 1,173 patients met eligibility criteria with a median of 27 months post-operative follow-up. The cumulative incidence of ≥10 % RVC at 24 months was 5.26 % (95 % CI 4.01-6.88 %). By multivariable analysis, a measurement of ≥5 to <10 % RVC occurring >3 months after surgery was significantly associated with an increased risk of progression to ≥10 % RVC (HR 2.97, p < 0.0001), but a measurement of ≥3 to <5 % RVC during the same time period was not statistically significantly associated (HR 1.55, p = 0.10). Other significant risk factors included a measurement ≤3 months after surgery with RVC of ≥3 to <5 % (p = 0.007), ≥5 to <10 % (p < 0.0001), or ≥10 % (p = 0.023), axillary lymph node dissection (ALND) (p < 0.0001), and higher BMI at diagnosis (p = 0.0028). Type of breast surgery, age, number of positive or number of lymph nodes removed, nodal radiation, chemotherapy, and hormonal therapy were not significant (p > 0.05). Breast cancer patients who experience a relative arm volume increase of ≥3 to <5 % occurring >3 months after surgery do not have a statistically significant increase in risk of progression to ≥10 %, a common lymphedema criterion. Our data support utilization of a ≥5 to <10 % threshold for close monitoring or intervention, warranting further assessment. Additional risk factors for progression to ≥10 % include ALND, higher BMI, and post-operative arm volume elevation.

Cording following treatment for breast cancer.

Treatment for breast cancer may result in the formation of palpable cords in the axillary region. Our aim was to evaluate cording incidence, risk factors, and association with upper extremity functional impairment and measured arm volume change. We included 308 patients with unilateral breast cancer prospectively screened for upper extremity lymphedema, symptoms and function. Patients were assessed pre- and post-operatively and at 3-8-month intervals with perometer arm measurements and the LEFT-BC questionnaire. Cording was determined by patient self-report. The cumulative incidence of cording and its association with clinicopathologic factors, upper extremity functional impairment, and measured arm volume change were analyzed. 31.5 % (97/308) of patients reported cording, with a cumulative incidence of 36.2 % at 24 months post-operative. Clinicopathologic factors significantly associated with cording by multivariate analysis included axillary lymph node dissection (p < 0.0001) and younger age at diagnosis (p = 0.0005). Cording was associated with increased functional impairment (p = 0.0018) and an arm volume increase of ≥5 % (p = 0.028). Cording following breast cancer treatment is common, and may occur beyond the post-operative period. Our findings emphasize the importance of identifying patients at high risk for cording, and developing strategies to minimize functional impairment and arm volume elevation associated with cording. Future studies should investigate the effectiveness of interventions for cording following breast cancer treatment.

Lymphedema following treatment for breast cancer: a new approach to an old problem.

Lymphedema following treatment for breast cancer can be an irreversible condition with a profound negative impact on quality of life. The lack of consensus regarding standard definitions of clinically significant lymphedema and optimal methods of measurement and quantification are unresolved problems. Inconsistencies persist regarding the appropriate timing of intervention and what forms of treatment should be the standard of care. There are reports that early detection and intervention can prevent progression, however,the Level 1 evidence to support this hypothesis has yet to be generated. To assess these controversies, we propose the implementation of a screening program to detect early lymphedema in conjunction with a randomized, prospective trial designed to generate Level 1 evidence regarding the efficacy of early intervention and appropriate treatment strategies. Collaboration among institutions that manage breast cancer patients is essential to establish a standardized approach to lymphedema and to establish guidelines for best practice.

Residual lymph node disease after neoadjuvant chemotherapy predicts an increased risk of lymphedema in node-positive breast cancer patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Sentinel lymph node biopsy at the time of mastectomy does not increase the risk of lymphedema: implications for prophylactic surgery.

Women diagnosed with or at high risk for breast cancer increasingly choose prophylactic mastectomy. It is unknown if adding sentinel lymph node biopsy (SLNB) to prophylactic mastectomy increases the risk of lymphedema. We sought to determine the risk of lymphedema after mastectomy with and without nodal evaluation. 117 patients who underwent bilateral mastectomy were prospectively screened for lymphedema. Perometer arm measurements were used to calculate weight-adjusted arm volume change at each follow-up. Of 234 mastectomies performed, 15.8 % (37/234) had no axillary surgery, 63.7 % (149/234) had SLNB, and 20.5 % (48/234) had axillary lymph node dissection (ALND). 88.0 % (103/117) of patients completed the LEFT-BC questionnaire evaluating symptoms associated with lymphedema. Multivariate analysis was used to assess clinical characteristics associated with increased weight-adjusted arm volume and patient-reported lymphedema symptoms. SLNB at the time of mastectomy did not result in an increased mean weight-adjusted arm volume compared to mastectomy without axillary surgery (p = 0.76). Mastectomy with ALND was associated with a significantly greater mean weight-adjusted arm volume change compared to mastectomy with SLNB (p < 0.0001) and without axillary surgery (p = 0.0028). Patients who underwent mastectomy with ALND more commonly reported symptoms associated with lymphedema compared to those with SLNB or no axillary surgery (p < 0.0001). Patients who underwent mastectomy with SLNB or no axillary surgery reported similar lymphedema symptoms. Addition of SLNB to mastectomy is not associated with a significant increase in measured or self-reported lymphedema rates. Therefore, SLNB may be performed at the time of prophylactic mastectomy without an increased risk of lymphedema.

Comparison of relative versus absolute arm size change as criteria for quantifying breast cancer-related lymphedema: the flaws in current studies and need for universal methodology.

The purpose of this article is to evaluate arm measurements of breast cancer patients to critically assess absolute change in arm size compared to relative arm volume change as criteria for quantifying breast cancer-related lymphedema (BCRL). We used pre-operative measurements of 677 patients screened for BCRL before and following treatment of unilateral breast cancer at Massachusetts General Hospital between 2005 and 2008 to model the effect of an absolute change in arm size of 200 mL or 2 cm compared to relative arm volume change. We also used sequential measurements to analyze temporal variation in unaffected arm volume. Pre-operative arm volumes ranged from 1,270 to 6,873 mL and correlated strongly (Kendall's τ = 0.55) with body mass index (BMI). An absolute arm volume change of 200 mL corresponded to relative arm volume changes ranging from 2.9 to 15.7 %. In a subset of 45 patients, modeling of a 2-cm change in arm circumference predicted relative arm volume changes ranging from 6.0 to 9.8 %. Sequential measurements of 124 patients with >6 measurements demonstrated remarkable temporal variation in unaffected arm volume (median within-patient change 10.5 %). The magnitude of such fluctuations correlated (τ = 0.36, P < 0.0001) with pre-operative arm volume, patient weight, and BMI when quantified as absolute volume change, but was independent of these variables when quantified as relative arm volume change (P > .05). Absolute changes in arm size used as criteria for BCRL are correlated with pre-operative and temporal changes in body size. Therefore, utilization of absolute volume or circumference change in clinical trials is flawed because specificity depends strongly on patient body size. Relative arm volume change is independent of body size and should thus be used as the standard criterion for diagnosis of BCRL.