A retrospective analysis of commonly prescribed medications and the risk of developing breast cancer related lymphedema.

OBJECTIVES: Breast cancer related lymphedema (BCRL) is a common complication of current breast cancer treatment modalities, significantly lowering quality of life for these patients and often leading to recurrent infections. Here, based on pre-clinical literature, we aim to retrospectively evaluate the risks of prescribed medications on BCRL development. METHODS: All post-operative breast cancer patients who received radiotherapy from 2005-2013 at Massachusetts General Hospital and developed lymphedema(n=115) were included in the analysis. Comparable patients without lymphedema(n=230) were randomly selected as control. The following classes of medications were analyzed: NSAIDs, corticosteroids, angiotensin system inhibitors, calcium channel blockers and hormonal therapy. Known risk factors for lymphedema development were included as variables, including BMI, age at diagnosis, type of surgery, number of lymph nodes removed and radiation therapy. Outcomes were BCRL development and lymphedema severity. RESULTS: Similarly, to previous studies, we found that an increase in BMI increases the risk of BCRL(p=0.006) and axillary lymph node dissection has a higher risk of developing BCRL compared to sentinel lymph node biopsy(p=0.045). None of the drugs studied increased the risk of BCRL development or lymphedema severity. However, lymphedema severity was positively correlated with the number of lymph nodes removed(p=0.034). CONCLUSION: We found that anti-inflammatory drugs, anti-hypertensive drugs and hormonal therapy taken during the year postoperatively do not increase the risk of BCRL development or lymphedema severity in breast cancer patients. While others have demonstrated that the number of lymph nodes removed during surgery increases the risk of BCRL, we found it also correlates to lymphedema severity.

Timing of Lymphedema After Treatment for Breast Cancer: When Are Patients Most At Risk?

PURPOSE: The purpose of the study was to determine when the risk of lymphedema is highest after treatment of breast cancer and which factors influence the time course of lymphedema development. METHODS AND MATERIALS: Between 2005 and 2017, 2171 women (with 2266 at-risk arms) who received surgery for unilateral or bilateral breast cancer at our institution were enrolled. Perometry was used to objectively assess limb volume preoperatively, and lymphedema was defined as a ≥10% relative arm-volume increase arising >3 months postoperatively. Multivariable regression was used to uncover risk factors associated with lymphedema, the Cox proportional hazards model was used to calculate lymphedema incidence, and the semiannual hazard rate of lymphedema was calculated. RESULTS: With a median follow-up of 4 years, the overall estimated 5-year cumulative incidence of lymphedema was 13.7%. Significant factors associated with lymphedema on multivariable analysis were high preoperative body mass index, axillary lymph node dissection (ALND), and regional lymph node radiation (RLNR). Patients receiving ALND with RLNR experienced the highest 5-year rate of lymphedema (31.2%), followed by those receiving ALND without RLNR (24.6%) and sentinel lymph node biopsy with RLNR (12.2%). Overall, the risk of lymphedema peaked between 12 and 30 months postoperatively; however, the time course varied as a function of therapy received. Early-onset lymphedema (<12 months postoperatively) was associated with ALND (HR [hazard ratio], 4.75; P < .0001) but not with RLNR (HR, 1.21; P = .55). In contrast, late-onset lymphedema (>12 months postoperatively) was associated with RLNR (HR, 3.86; P = .0001) and, to a lesser extent, ALND (HR, 1.86; P = .029). The lymphedema risk peaked between 6 and 12 months in the ALND-without-RLNR group, between 18 and 24 months in the ALND-with-RLNR group, and between 36 and 48 months in the group receiving sentinel lymph node biopsy with RLNR. CONCLUSIONS: The time course for lymphedema development depends on the breast cancer treatment received. ALND is associated with early-onset lymphedema, and RLNR is associated with late-onset lymphedema. These results can influence clinical practice to guide lymphedema surveillance strategies and patient education.

Hand Edema in Patients at Risk of Breast Cancer-Related Lymphedema: Health Professionals Should Take Notice.

Background: There is little research on hand edema in the population at risk for breast cancer-related lymphedema (BCRL). Objectives: Study aims included reporting potential importance of hand edema (HE) as a risk factor for progression of edema in patients treated for breast cancer at risk for BCRL, reporting risk factors for BCRL, and reporting treatment of HE. Design/Methods: This was a retrospective analysis of 9 patients treated for breast cancer in Massachusetts General Hospital's lymphedema screening program who presented with isolated HE. Limb volumes via perometry, BCRL risk factors, and HE treatment are reported. Results: Edema was mostly isolated to the hand. Three patients had arm edema >5% on perometry; and 2 of these had edema outside the hand on clinical examination. Patients were at high risk of BCRL with an average of 2.9/5 known risk factors. Arm edema progressed to >10% in 2 high-risk patients. Treatment resulted in an average hand volume reduction of 10.2% via perometry and improvement upon clinical examination. Limitations: The small sample size and lack of validated measures of subjective data were limitations. Conclusions: In this cohort, patients with HE carried significant risk factors for BCRL. Two out of 9 (22%), both carrying ≥4/5 risk factors, progressed to edema >10%. Isolated HE may be a prognostic factor for edema progression in patients treated for breast cancer at risk for BCRL. Further research is warranted.

Association Between Precautionary Behaviors and Breast Cancer-Related Lymphedema in Patients Undergoing Bilateral Surgery.

Purpose This study examined the lifestyle and clinical risk factors for lymphedema in a cohort of patients who underwent bilateral breast cancer surgery. Patients and Methods Between 2013 and 2016, 327 patients who underwent bilateral breast cancer surgery were prospectively screened for arm lymphedema as quantified by the weight-adjusted volume change (WAC) formula. Arm perometry and subjective data were collected preoperatively and at regular intervals postoperatively. At the time of each measurement, patients completed a risk assessment survey that reported the number of blood draws, injections, blood pressure readings, trauma to the at-risk arm, and number of flights since the previous measurement. Generalized estimating equations were applied to ascertain the association among arm volume changes, clinical factors, and risk exposures. Results The cohort comprised 327 patients and 654 at-risk arms, with a median postoperative follow-up that ranged from 6.1 to 68.2 months. Of the 654 arms, 83 developed lymphedema, defined as a WAC ≥ 10% relative to baseline. On multivariable analysis, none of the lifestyle risk factors examined through the risk assessment survey were significantly associated with increased WAC. Multivariable analysis demonstrated that having a body mass index ≥ 25 kg/m2 at the time of breast cancer diagnosis ( P = .0404), having undergone axillary lymph node dissection ( P = .0464), and receipt of adjuvant chemotherapy ( P = .0161) were significantly associated with increased arm volume. Conclusion Blood pressure readings, blood draws, injections, and number or duration of flights were not significantly associated with increases in arm volume in this cohort. These findings may help to guide patient education about lymphedema risk reduction strategies for those who undergo bilateral breast cancer surgery.

Diagnostic Methods, Risk Factors, Prevention, and Management of Breast Cancer-Related Lymphedema: Past, Present, and Future Directions.

PURPOSE OF REVIEW: Breast cancer-related lymphedema (BCRL) is a chronic, adverse, and much feared complication of breast cancer treatment, which affects approximately 20% of patients following breast cancer treatment. BCRL has a tremendous impact on breast cancer survivors, including physical impairments and significant psychological consequences. The intent of this review is to discuss recent studies and analyses regarding the risk factors, diagnosis, prevention through early screening and intervention, and management of BCRL. RECENT FINDINGS: Highly-evidenced risk factors for BCRL include axillary lymph node dissection, lack of reconstruction, radiation to the lymph nodes, high BMI at diagnosis, weight fluctuations during and after treatment, subclinical edema within and beyond 3 months after surgery, and cellulitis in the at-risk arm. Avoidance of potential risk factors can serve as a method of prevention. Through establishing a screening program by which breast cancer patients are measured pre-operatively and at follow-ups, are objectively assessed through a weight-adjusted analysis, and are clinically assessed for signs and symptoms, BCRL can be tracked accurately and treated effectively. Management of BCRL is done by a trained professional, with research mounting towards the use of compression bandaging as a first line intervention against BCRL. Finally, exercise is safe for breast cancer patients with and without BCRL and does not incite or exacerbate symptoms of BCRL. SUMMARY: Recent research has shed light on BCRL risk factors, diagnosis, prevention, and management. We hope that education on these aspects of BCRL will promote an informed, consistent approach and encourage additional research in this field to improve patient outcomes and quality of life in breast cancer survivors.

Precautions for breast cancer-related lymphoedema: risk from air travel, ipsilateral arm blood pressure measurements, skin puncture, extreme temperatures, and cellulitis.

Precautionary recommendations conveyed to survivors of cancer by health-care practitioners to reduce the risk of breast cancer-related lymphoedema are indispensable aspects of clinical care, yet remain unsubstantiated by high-level scientific evidence. By reviewing the literature, we identified 31 original research articles that examined whether lifestyle-associated risk factors (air travel, ipsilateral arm blood pressure measurements, skin puncture, extreme temperatures, and skin infections-eg, cellulitis) increase the risk of breast cancer-related lymphoedema. Among the few studies that lend support to precautionary guidelines, most provide low-level (levels 3-5) or inconclusive evidence of an association between lymphoedema and these risk factors, and only four level 2 studies show a significant association. Skin infections and previous infection or inflammation on the ipsilateral arm were among the most clearly defined and well established risk factors for lymphoedema. The paucity of high-level evidence and the conflicting nature of the existing literature make it difficult to establish definitive predictive factors for breast cancer-related lymphoedema, which could be a considerable source of patient distress and anxiety. Along with further research into these risk factors, continued discussion regarding modification of the guidelines and adoption of a risk-adjusted approach is needed.

A comprehensive review of bioimpedance spectroscopy as a diagnostic tool for the detection and measurement of breast cancer-related lymphedema.

As treatment for breast cancer improves and the threat of life-long chronic lymphedema becomes more prevalent, the need for effective screening tools emerges as crucial. This review was conducted using literature beginning in 1992 to analyze primary research testing the accuracy of bioimpedance spectroscopy as a diagnostic and early detection tool for breast cancer-related lymphedema. We concluded bioimpedance is an accurate diagnostic tool for pre-existent lymphedema, however, it has not been validated for early detection. J. Surg. Oncol. 2016;114:537-542. © 2016 Wiley Periodicals, Inc.

The need for preoperative baseline arm measurement to accurately quantify breast cancer-related lymphedema.

Breast cancer-related lymphedema (BCRL) is a feared outcome of breast cancer treatment, yet the push for early screening is hampered by a lack of standardized quantification. We sought to determine the necessity of preoperative baseline in accounting for temporal changes of upper extremity volume. 1028 women with unilateral breast cancer were prospectively screened for lymphedema by perometry. Thresholds were defined: relative volume change (RVC) ≥10 % for clinically significant lymphedema and ≥5 % including subclinical lymphedema. The first postoperative measurement (pseudo-baseline) simulated the case of no baseline. McNemar's test and binomial logistic regression models were used to analyze BCRL misdiagnoses. Preoperatively, 28.3 and 2.9 % of patients had arm asymmetry of ≥5 and 10 %, respectively. Without baseline, 41.6 % of patients were underdiagnosed and 40.1 % overdiagnosed at RVC ≥ 5 %, increasing to 50.0 and 54.8 % at RVC ≥ 10 %. Increased pseudo-baseline asymmetry, increased weight change between baselines, hormonal therapy, dominant use of contralateral arm, and not receiving axillary lymph node dissection (ALND) were associated with increased risk of underdiagnosis at RVC ≥ 5 %; not receiving regional lymph node radiation was significant at RVC ≥ 10 %. Increased pseudo-baseline asymmetry, not receiving ALND, and dominant use of ipsilateral arm were associated with overdiagnosis at RVC ≥ 5 %; increased pseudo-baseline asymmetry and not receiving ALND were significant at RVC ≥ 10 %. The use of a postoperative proxy even early after treatment results in poor sensitivity for identifying BCRL. Providers with access to patients before surgery should consider the consequent need for proper baseline, with specific strategy tailored by institution.

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.

Establishing and sustaining a prospective screening program for breast cancer-related lymphedema at the massachusetts general hospital: lessons learned.

There has been an increasing call to prospectively screen patients with breast cancer for the development of breast cancer-related lymphedema (BCRL) following their breast cancer treatment. While the components of a prospective screening program have been published, some centers struggle with how to initiate, establish, and sustain a screening program of their own. The intent of this manuscript is to share our experience and struggles in establishing a prospective surveillance program within the infrastructure of our institution. It is our hope that by sharing our history other centers can learn from our mistakes and successes to better design their own prospective screening program to best serve their patient population.

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.