Clinical Investigation
Factors Associated With the Development of Breast Cancer–Related Lymphedema After Whole-Breast Irradiation

https://doi.org/10.1016/j.ijrobp.2011.09.058Get rights and content

Purpose

To determine the rates of breast cancer–related lymphedema (BCRL) in patients undergoing whole-breast irradiation as part of breast-conserving therapy (BCT) and to identify clinical, pathologic, and treatment factors associated with its development.

Methods and Materials

A total of 1,861 patients with breast cancer were treated at William Beaumont Hospital with whole-breast irradiation as part of their BCT from January 1980 to February 2006, with 1,497 patients available for analysis. Determination of BCRL was based on clinical assessment. Differences in clinical, pathologic, and treatment characteristics between patients with BCRL and those without BCRL were evaluated, and the actuarial rates of BCRL by regional irradiation technique were determined.

Results

The actuarial rate of any BCRL was 7.4% for the entire cohort and 9.9%, 14.7%, and 8.3% for patients receiving a supraclavicular field, posterior axillary boost, and internal mammary irradiation, respectively. BCRL was more likely to develop in patients with advanced nodal status (11.4% vs. 6.3%, p = 0.001), those who had a greater number of lymph nodes removed (14 nodes) (9.5% vs. 6.0%, p = 0.01), those who had extracapsular extension (13.4% vs. 6.9%, p = 0.009), those with Grade II/III disease (10.8% vs. 2.9%, p < 0.001), and those who received adjuvant chemotherapy (10.5% vs. 6.7%, p = 0.02). Regional irradiation showed small increases in the rates of BCRL (p = not significant).

Conclusions

These results suggest that clinically detectable BCRL will develop after traditional BCT in up to 10% of patients. High-risk subgroups include patients with advanced nodal status, those with more nodes removed, and those who receive chemotherapy, with patients receiving regional irradiation showing a trend toward increased rates.

Introduction

The incidence of breast cancer in the United States is approximately 200,000 cases per year, with up to 2.4 million women having a history of the disease (1). As outcomes continue to improve, so do the number of long-term survivors of breast cancer; therefore long-term toxicities affecting quality of life, such as breast cancer–related lymphedema (BCRL), are gaining greater importance.

Limited data exist on the risk of BCRL. On the basis of the therapeutic modalities used, rates reported using surgery, irradiation, and chemotherapy range from 5% with lumpectomy alone to up to 60% to 65% when treatment includes mastectomy with axillary lymph node dissection (ALND) and regional irradiation (2). Currently, up to 800,000 women have some form of BCRL based on incidence and prevalence rates of breast cancer and averaged rates of BCRL (2). Therefore analyses directed at identifying factors associated with its development and prevention are crucial.

Radiation therapy (RT) has been found to be a risk factor for the development of BCRL in multiple series, with a predominant focus on the role of regional irradiation 3, 4. Coen et al. (3) evaluated 727 patients who were treated with breast-conserving surgery and whole-breast irradiation (WBI) with or without the inclusion of regional lymphatics. The rate of BCRL at 10 years, defined as a difference in forearm circumference of greater than 2 cm, was 2% with tangents alone and 9% when regional nodal volumes were included, with axillary radiation as the only associated factor (3). In an evaluation of 2,579 women who received RT to the breast, the breast and supraclavicular region, or the breast, supraclavicular region, and posterior axillary boost, the rates of BCRL were 16%, 23%, and 31%, respectively. Risk factors identified included the addition of regional nodal irradiation, increasing weight, chemotherapy, and the number of nodes dissected (4). However, at this time, there are limited long-term data evaluating factors predictive of BCRL in patients undergoing RT.

The purpose of this analysis was to examine clinical, pathologic, and treatment factors associated with the development of BCRL after WBI and to identify high-risk patient groups who may benefit from aggressive interventions before the development of BCRL.

Section snippets

Methods and Materials

A total of 1,861 patients with breast cancer were treated at William Beaumont Hospital with WBI as part of their breast-conserving therapy from January 1980 to February 2006. Patients were prospectively entered into an institutional review board–approved database with pertinent patient, pathologic, treatment, and outcome data, including follow-up data, through September 2010. A total of 1,497 patients were available for analysis after the exclusion of patients with ductal carcinoma in situ,

Results

A total of 1,497 patients were available for evaluation. Patient characteristics for our study cohort are presented in Table 1. The majority of patients were white (92%), and only 29% of patients were under 50 years old. Nearly three-quarters of tumors were smaller than 2.0 cm, and 99% were 5.0 cm or less. Of note, three-quarters of patients had N0 disease; however, the mean and median number of axillary nodes sampled was 14 (range, 0–46). 24% received chemotherapy as neoadjuvant or adjuvant

Discussion

The results of this analysis show that the addition of regional irradiation (supraclavicular, posterior axillary, or internal mammary field) to WBI is not associated with a statistically significant increase in the incidence of BCRL. However, trends for increased rates were seen with the inclusion of supraclavicular and posterior axillary fields, suggesting that with increased numbers of patients examined, a relationship may exist. The true pathophysiology underlying BCRL is not fully

Conclusions

The results of this analysis show that nodal status, the number of nodes removed as part of an ALND, and administration of chemotherapy are associated with the development of BCRL. Regional irradiation appears to be associated with the development of BCRL based on previous series and the trends seen in this analysis. High-risk subgroups of patients can be identified and may potentially benefit from prophylactic treatment and surveillance with new diagnostic modalities.

References (18)

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Conflict of interest: none.

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