Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy

Abstract

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1–54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92–18.16) and 3.9 (1.60–9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Lymphedema and Axillary Sentinel Lymph Node Biopsy (SLNB) in Node-Negative Patients with Breast Cancer

“…Sentinel lymph node biopsy-negative patients may exhibit mild lymphedema, but if untreated, it can become more severe. However, in our study, severe lymphedema was diagnosed in 4% of patients, which falls within the recorded range of 0.2% to 9% in SLNB patients with lymphedema in some studies (15,(32)(33)(34)(35). Therapists and clinicians should consider lymphedema as a complication when evaluating patients who have had SLNB.…”

The Vicious Circle of Stasis, Inflammation, and Fibrosis in Lymphedema

“…27 This concept makes intuitive sense because lymphedema rarely occurs in patients with cancer who are treated nonsurgically or who undergo limited lymph node dissection (eg, sentinel lymph node biopsy). 9,28 However, research over the past 10 years suggests that lymphatic injury is only the initiating step that, in a subset of patients, activates additional pathologic mechanisms that regulate the development of lymphedema. 29 This hypothesis is supported by the fact that lymphedema develops in some surgical patients but not others treated in an identical manner.…”

“…6 Breast cancer, owing to its high incidence and tendency for lymph node metastasis, is the most common cause of lymphedema in Western countries, developing in 15% to 40% of all patients who undergo axillary lymph node dissection. [7][8][9] This variable incidence of breast cancer-related lymphedema can be attributed to differing diagnostic criteria that are used and the length of follow-up. 1 Secondary lymphedema is not limited to breast cancer and can also develop in patients treated for other solid malignancies, including sarcoma, gynecologic or urologic tumors, and malignant melanoma.…”

Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial)

“…Axillary lymph node status is an important prognostic factor that may contribute to decisions about adjuvant therapy. Although axillary lymph node dissection (ALND) allows us to achieve locoregional disease control, it causes adverse functional sequelae, including lymphedema and restricted shoulder mobility, in a non-negligible percentage of patients ( 1 , 2 ). Furthermore, the contribution of ALND to breast cancer survival is controversial, leading to selective sentinel lymph node biopsy (SLNB) becoming the standard approach in patients with invasive breast cancer and no lymph node involvement at diagnosis (cN0).…”