J. O'Toole

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.

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.

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.

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.

Screening for Breast Cancer-Related Lymphedema: The Need for Standardization

This commentary explores the challenges surrounding the development of a standard definition of lymphedema and method of quantification, proposes solutions, and calls for a collaborative effort among providers who care for patients with breast cancer.

Abstract PD4-5: Blood draws, injections, blood pressure readings in the at-risk arm, and flying might not be associated with increases in arm volume: A prospective study

Introduction: Breast cancer related lymphedema (BCRL) is a swelling caused by compromise of the lymphatic system after breast cancer treatment. Commonly-cited risk factors include treatment related variables such as axillary lymph node dissection (ALND) and regional lymph node radiation (RLNR), and patient characteristics including BMI. Patients are often advised to avoid blood draws, injections, and blood pressure cuffs on their at-risk arm, airplane travel, and extensive exercise to reduce the risk of developing BCRL; however, data demonstrating the efficacy of such avoidance strategies do not exist. We sought to determine the impact of blood draws, injections, and blood pressure readings in the at-risk arm, and flying on increases in arm volume in a large, prospective cohort of patients. Methods: 522 patients who underwent treatment for unilateral breast cancer between were included. Patients were prospectively screened for BCRL with Perometer arm measurements pre-operatively, post-operatively, and at 3-8 month intervals thereafter. At each measurement patients were asked to report number of blood draws, injections, and blood pressure readings in the at-risk arm, and number of flights since the last measurement, and their responses were assessed for association with relative volume change (RVC). RVC was analyzed as a continuous variable for association with risk factors. Results: 522 patients with 2033 post operative measurements were included. Patients were followed for a median of 23 months and 4 post-operative measurements, with a minimum of 1 post-operative measurement and a maximum of 14. 5.56%. 76.8% (401/522) underwent lumpectomy, 23.2% (121/522) underwent mastectomy. 70% (366/522) underwent sentinel lymph node biopsy, and 19% (98/522) underwent ALND. 62.4% (352/521) received radiation to the breast/ chest wall only, and 21.5% (112/521) also received regional lymph node radiation. By univariate analysis, there was no significant association between RVC increase and undergoing one or more blood draws (p=0.36), blood pressure (p=0.88), injections (p=0.79), or number of flights (p=0.89). ALND was significantly associated with increases in arm volume (p=0.0017) by univariate analysis and older age at diagnosis was associated with increased RVC with borderline significance (p=0.059). Conclusions: In our patient population, non-treatment related risk factors including blood draws, blood pressures, and injections in the at-risk arm, and flying were not significantly associated with increases in arm volume. This data can be used to help improve and refine patient education regarding the importance of risk-reducing practices after breast cancer treatment. Citation Format: Chantal M Ferguson, Cynthia L Miller, Nora Horick, Melissa N Skolny, Meyha N Swaroop, Lauren S Jammallo, Jean A O9Toole, Michelle C Specht, Alphonse G Taghian. Blood draws, injections, blood pressure readings in the at-risk arm, and flying might not be associated with increases in arm volume: A prospective study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD4-5.

Abstract P1-09-13: Risk of breast cancer related lymphedema after treatment with taxane-based chemotherapy: A prospective cohort study

Background: Taxane-based chemotherapy is routinely used in the treatment of breast cancer and has been shown to improve both disease-free survival (DFS) and overall survival (OS). A common side effect of taxane-based chemotherapy is fluid retention in the extremities, which may increase the risk of breast cancer related lymphedema (BCRL). BCRL is a chronic swelling of the arms, breast, or trunk due to accumulation of lymphatic fluid in the interstitial tissues, which has a profoundly negative impact on quality of life. Little data exists regarding the impact of taxane-based chemotherapy and fluid retention on risk of developing BCRL. We sought to determine whether receipt of taxane-based chemotherapy for the treatment of breast cancer increases the risk of BCRL development in a large, prospective cohort of breast cancer patients. Methods: We identified 569 patients diagnosed with unilateral breast cancer between 2005-2012 who underwent surgery and prospective screening for BCRL at our institution. All patients included in this analysis had ≥ 18 months of post-operative follow-up. Bilateral arm volume measurements were performed using a perometer preoperatively and every 3-7 months postoperatively. BCRL was defined as a relative volume change (RVC) of ≥10%. Clinicopathologic characteristics and treatment details were obtained by medical record review. Cox proportional hazard analyses were performed to analyze risk of BCRL. Arm measurements obtained after contralateral prophylactic surgery or diagnosis of metastasis were excluded to avoid potential confounding. Results: Arm volume measurements from 569 patients were included with a median post-operative follow-up of 28 months (range 18-75.1). 33% (187/569) of patients received taxane-based chemotherapy in the neoadjuvant and/or adjuvant setting, and 92% (172/187) of these patients received pre-medication with dexamethasone to prevent hypersensitivity and reduce edema. 3% (18/569) received non-taxane based chemotherapy and 64% (364/569) received no chemotherapy. 23% (131/569) had axillary lymph node dissection (ALND), 61% (346/569) had sentinel lymph node biopsy (SLNB), and 16% (92/569) had no nodal surgery. At 24 months, the cumulative incidence of BCRL was 5.0% (95% CI: 3.15-7.81%) among patients who did not receive taxane-based chemotherapy, compared to 13.4% (95% CI: 9.17-19.4%) in the taxane-based chemotherapy group. On univariate analysis, taxane-based chemotherapy was associated with increased risk of BCRL (HR=2.2, p=0.0037), in addition to ALND, higher body mass index, greater number of lymph nodes (LNs) dissected and greater number of positive LNs (p Conclusion: Our results suggest that patients who receive taxane-based chemotherapy are not at an increased risk of BCRL compared with patients who received non-taxane or no chemotherapy. This data can be used to improve patient education and counsel those who experience temporary fluid retention while on taxane-based chemotherapy. Citation Format: Meyha N Swaroop, Cynthia L Miller, Nora Horick, Chantal M Ferguson, Melissa N Skolny, Jean O9Toole, Lauren S Jammallo, Michelle C Specht, Alphonse G Taghian. Risk of breast cancer related lymphedema after treatment with taxane-based chemotherapy: A prospective cohort study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-13.

Abstract P6-09-04: The Association of Low Level Arm Volume Increases with Lymphedema Symptoms Following Treatment for Breast Cancer

Purpose/Objective: The symptoms associated with breast cancer-related lymphedema are well-documented, and include sensations of heaviness, swelling, and tightness in the upper extremity and trunk. However, the clinical significance of low-level arm volume changes frequently experienced by breast cancer patients is not well understood. We sought to determine the association of low level arm volume changes with patient-reported lymphedema symptoms in women treated for breast cancer. Methods: 267 patients who underwent surgical treatment for breast cancer from 2010–2012 were identified from a cohort of patients prospectively screened for lymphedema at our institution. Patients were assessed with perometer arm volume measurements and a survey of lymphedema symptoms pre and post operatively, and at 3–7 month intervals thereafter. Inclusion in this analysis was limited to unilaterally affected women with ≥ 3 assessments and ≥ 6 months of post-surgical follow-up. Arm volume changes were quantified as Relative Volume Change (RVC): RVC = (A2*U1)/(U2*A1) − 1, where A1 is pre-operative arm volume and A2 is post-operative arm volume on the affected side, and U1 and U2 are arm volumes on the unaffected side at these time points. Low level arm volume change was defined as a measurement with RVC ≥ 5% Results: Low level arm volume changes occurred in 21.7% (58/267) of patients during the follow-up period at a median of 10.4 months post-operatively. Median post-operative follow-up was 12.4 months and 5 assessments per patient. By actuarial univariate analysis, symptoms of larger arm, shoulder, or neck (p Conclusions: This data suggests that patients may be symptomatic for lymphedema even when experiencing low level arm volume changes. These patients should be followed closely for progression of measured arm volume or heightened lymphedema symptoms suggesting progression of the condition. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-09-04.

Abstract OT3-2-02: The PREDICT Study (Prospective, Randomized Early Detection and Intervention after Breast Cancer-Treatment, for women at risk of lymphedema)

Introduction: It is well-documented that lymphedema is one of the most feared long-term side effects of breast cancer (BC) treatment. However, to date, a standardized approach for the quantification and treatment of breast cancer-related lymphedema (BCRL) has yet to be established. Aims: We propose a screening and intervention trial that will assess the efficacy of early detection and intervention for BCRL. Intervention comprises the use of compression garments for mild lymphedema and compression garments +/− nighttime bandaging for moderate lymphedema. Other factors to be evaluated include: symptom clusters, treatment adherence, fear avoidance behavior, quality of life (QOL), upper extremity function, and risk factors for BCRL. Eligibility Criteria: Women 18 years + with a confirmed BC diagnosis, no history of BC, no known metastatic or locally advanced disease, no history of primary lymphedema, sentinel lymph node biopsy or axillary lymph node dissection as part of definitive breast surgery. Study Design: A two-stage study which includes a Screening and an Intervention trial. The screening arm will evaluate arm volume change during and after BC treatment with target accrual of 8000. Patients will undergo measurements via perometry and complete the MGH Lymphedema Evaluation Following Treatment for Breast Cancer (LEFT-BC) Survey at each screening appointment to evaluate changes in functionality, upper extremity utilization (fear associated avoidance), and QOL. Screening visits will occur pre- and post - operatively, at the conclusion of chemotherapy and radiation therapy and every 3–7 months thereafter. Patients will become eligible for enrollment into the intervention trial if, during the course of screening, they develop a relative arm volume change (RVC) of ≥ 5% which persists at a verification measurement within 4–8 weeks. Eligible subjects are enrolled into one of two groups based on verification RVC: Group I – Mild Lymphedema (5–10% RVC) or Group II – Moderate Lymphedema (11–20% RVC). Subjects are then randomized within each group. Group I subjects are randomized to one of two arms: I-A – Observation, I-B – Compression, and Group II subjects are randomized to one of two arms: II-A – Compression, II-B – Compression + Night Compression Bandaging. Target accrual for the intervention trial is 336 subjects (Group I: 208, Group II: 128). Clinical Relevance: The results of this study will yield level I evidence on the effectiveness of early detection and intervention for BCRL. Findings may shape clinical practice in diagnosis and treatment, as well as provide insight regarding the risk factors, symptoms, upper extremity function, and quality of life (QOL) associated with BCRL. *Funding by awards R01CA139118 & 3P5OCA089393, AGT Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-2-02.

P5-17-03: The Association between Breast Cancer Related Lymphedema's Risk Factors and Likelihood of Edema Progression.

Purpose/Objective(s): Breast cancer related lymphedema (BCRL) is one of the most feared long term side effects of treatment. Although emergence of the sentinel lymph node biopsy (SLNB) has decreased the rate of BCRL, it continues to be an issue for this population. The goal of this study is to evaluate the prognostic risk factors for BCRL development and progression based on longitudinal prospective limb volume (LV) measurements and associated surgical, radiation and medical oncology factors. Materials/Methods: Since 2005 newly diagnosed breast cancer (BC) patients were prospectively screen via perometery (Pero-System). For this analysis patients were required to have undergone at least four measurements and have at least 24 months of follow up to allow for adequate time for LE development. Bilateral pre-operative volume measurements of the upper extremity were compared to postoperative measurements and at 4 to 6 month intervals to assess for limb volume changes. At each time point (tx), relative volume change (RVC) of the treated arm was calculated using volume ratios of treated (T) to non-treated (N) side compared to the pre-operative baseline (t1) (RVC=(Ttx/Ntx)/(Tt1/Nt1)-1) as described in Ancukiewicz et al 2010. Our institution utilizes >5% RVC as an indicator of lymphedema. For this analysis, mild lymphedema was classified as a RVC of 5–9.9% and moderate lymphedema was classified as a RVC ≥ 10%. A univariate analysis was performed to identify risk factors and likelihood to LE progression. Results: In a cohort of 415 women, 14.4 %(60) and 6.7% (28) developed mild and moderate BCRL, respectively. Twenty percent (14) and 75 %(21) of patients in the mild and moderate cohorts, respectively, had a persistent edema that was documented at a least 2 consecutive data points. Eighty percent (56) and 25% (7) of patients that had a documented incidence of an elevated RVC had returned below an RVC Conclusion: Breast cancer related lymphedema is a feared long term side effects and negatively impacts the physical and psychological aspects of an individual9s life. A condition that is considered manageable but not curable, it is essential providers identify high risk individuals. Establishing a a lymphedema screening program may identify early lymphedema which could be potentially be treated successfully. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-17-03.