The Impact of Radiation Therapy on the Risk of Lymphedema After Treatment for Breast Cancer: A Prospective Cohort Study

Abstract

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.

A Cross-sectional Study Examining the Risk Factors Associated with Lymphedema and its Prevalence in Breast Cancer Patients after Level 3 Axillary Lymph Node Dissection

“…A study by Werner et al (33) explained that these opposing views were because of the more aggressive nature of breast cancer in young women, characterized by the higher incidence of lymphedema associated with intensive cancer treatment, and the vulnerability of young patients to infection and trauma-induced lymphedema because of a more active lifestyle. Many studies (2,10,13,15,28,32,34) have also reported that BMI is a significant risk factor for the development of lymphedema, and this study agrees with this conclusion. In a recent study, a significant reduction was observed in arm edema in patients whose body weight and BMI had decreased after a 12-week diet program, and the authors emphasized the importance of weight loss in the treatment of lymphedema (35).…”

“…However, it can also cause lymphedema by obstructing the lymphatic vessels with radiationinduced fibrosis (25). In some studies, radiotherapy of the breast region and axillary radiotherapy were found to be significant risk factors for lymphedema on univariate analysis; however, with multivariate analysis, only axillary radiotherapy was identified as a risk factor (7,10). We found similar results in our study with an increase in lymphedema development after axillary radiotherapy alone.…”

“…On the other hand, in recent years, sentinel lymph node dissection (SLND) has decreased the incidence of lymphedema because it allows for the detection of the first metastatic node, thereby limiting the number of ALNs extracted. On the other hand, the addition of adjuvant radiotherapy, particularly axillary radiotherapy, has been shown to increase the incidence of lymphedema (10). Despite the efforts to ensure breast cancer patients undergo conservative surgery and SLND, one-third of patients with breast cancer suffer from an invasive type of cancer; therefore, ALND and complications due to ALND is inevitable for these patients (11).…”

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update

“…RNI may increase the risk of lymphedema, especially in patients who also undergo ALND. 26,34 Furthermore, many more patients now undergo breast reconstructive surgery. Administration of PMRT can worsen cosmetic results and increase the risk of both shortand long-term complications.…”

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

“…Well-defined risk factors for developing lymphedema include axillary lymph node dissection (ALND), [9][10][11][12][13][14][15] regional lymph node irradiation (RLNR), 8,[16][17][18][19] higher body mass index (BMI), and older age at diagnosis. 7,8,11,14,[20][21][22][23][24][25][26][27][28][29][30] It remains unclear why, among patients with similar demographic and treatment-related characteristics, some go on to develop lymphedema.…”