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

Presented at the 55th Annual Meeting of the American Society for Radiation Oncology (ASTRO), Atlanta, GA, September 22-25, 2013.
https://doi.org/10.1016/j.ijrobp.2013.11.232Get rights and content

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.

Introduction

Women treated for breast cancer have increasingly successful outcomes; therefore, late toxicities of treatment are assuming greater importance. Lymphedema causes significant physical and psychosocial side effects and is of concern for women undergoing breast cancer therapy 1, 2, 3, 4. Data regarding the risk of lymphedema with the inclusion of adjuvant radiation therapy are limited and are often based on retrospective cohorts, varying definitions of lymphedema, and heterogeneous patient populations.

Of particular interest is the risk of lymphedema with extended radiation therapy fields. Regional lymph node radiation (RLNR) is routinely used in patients with ≥4 positive lymph nodes (LNs) found at the time of lumpectomy or mastectomy with axillary LN dissection (ALND) (5). These clinical practices are based on trials that demonstrated decreased rates of locoregional failure, increased disease-free survival (DFS), and increased overall survival (OS) for high-risk or LN-positive patients with the receipt of postmastectomy radiation therapy 6, 7. Inasmch as women undergoing RLNR most often also undergo sentinel LN biopsy (SLNB) or ALND, which have a reported incidence of lymphedema up to 11% and 30%, respectively 8, 9, 10, quantifying the additional risk with inclusion of RLNR has significant clinical implications.

In this study, we used a large cohort of breast cancer patients prospectively screened for lymphedema and analyzed arm volume changes to quantify the risk of lymphedema with inclusion of adjuvant radiation therapy. The types of radiation therapy analyzed included receipt of no radiation, partial breast irradiation (PBI), whole breast irradiation (WBI) or chest wall radiation alone, or WBI/chest wall radiation with RLNR. Among patients who received RLNR, we sought to determine whether the addition of a posterior axillary boost (PAB) to supraclavicular irradiation (SC) increased the risk of lymphedema compared with SC alone.

Section snippets

Patients

We included 1476 women who underwent surgery for unilateral or bilateral breast cancer from 2005 to 2012. Patients were recruited at the time of initial consultation in a multidisciplinary clinic, and all underwent surgery at our institution. All patients, regardless of T or N stage, were included except for patients with pre-existing lymphedema. Treating each breast individually, we had 1501 unique cases. Each patient had >3 months of postsurgical follow-up.

Lymphedema definition and measurement

According to the standard of care at

Results

Of the 1476 patients, 1262 (86%) underwent unilateral breast surgery and 214 (14%) underwent bilateral breast surgery for unilateral (n=189) or bilateral (n=25) breast cancer. Postoperative radiation therapy was given after 1099 of 1501 (73%) individual breast surgeries. The clinical and pathologic characteristics are given in Table 2. The median postoperative follow-up time was 25.4 months (range, 3.0-82.6 months), with a median of 4 postoperative measurements per patient (range, 1-25

Discussion

The current study used a cohort of 1476 breast cancer patients prospectively screened for lymphedema at a single institution. The patients in our study were treated for breast cancer between 2005 and 2012, and they thereby represent a population treated with modern radiation therapy and surgical techniques over a relatively short time. The risk factors for lymphedema, including adjuvant radiation therapy, have been previously evaluated; however, most studies have used retrospectively collected

Acknowledgment

The authors thank Nadine R. Taghian, whose continuous dedication helped expedite completion of this project, and whose efforts are greatly appreciated.

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    Supported by Award # RO1CA139118 (A. Taghian) and Award # P50CA0893932 (A. Taghian) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Cancer Institute or the National Institutes of Health.

    Conflict of interest: none.

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