Risk factors for lymphedema after breast cancer treatment

Abstract

Background: As cancer treatments evolve, it is important to reevaluate their effect on lymphedema risk in breast cancer survivors.

Methods: A population-based random sample of 631 women from metropolitan Philadelphia, Pennsylvania, diagnosed with incident breast cancer in 1999 to 2001, was followed for 5 years. Risk factor information was obtained by questionnaire and medical record review. Lymphedema was assessed with a validated questionnaire. Using Cox proportional hazards models, we estimated the relative incidence rates [hazard ratios (HR)] of lymphedema with standard adjusted multivariable analyses ignoring interactions, followed by models including clinically plausible treatment interactions.

Results: Compared with no lymph node surgery, adjusted HRs for lymphedema were increased following axillary lymph node dissection [ALND; HR, 2.61; 95% confidence interval (95% CI), 1.77-3.84] but not sentinel lymph node biopsy (SLNB; HR, 1.04; 95% CI, 0.58-1.88). Risk was not increased following irradiation [breast/chest wall only: HR, 1.18 (95% CI, 0.80-1.73); breast/chest wall plus supraclavicular field (+/- full axilla): HR, 0.86 (95% CI, 0.48-1.54)]. Eighty-one percent of chemotherapy was anthracycline based. The HR for anthracycline chemotherapy versus no chemotherapy was 1.46 (95% CI, 1.04-2.04), persisting after stratifying on stage at diagnosis or number of positive nodes. Treatment combinations involving ALND or chemotherapy resulted in approximately 4- to 5-fold increases in HRs for lymphedema [e.g., HR of 4.16 (95% CI, 1.32-12.45) for SLNB/chemotherapy/no radiation] compared with no treatment.

Conclusion: With standard multivariable analyses, ALND and chemotherapy increased lymphedema risk whereas radiation therapy and SLNB did not. However, risk varied by combinations of exposures.

Impact: Treatment patterns should be considered when counseling and monitoring patients for lymphedema.

Figure 1

Estimated cumulative incidence of lymphedema according to different treatment scenarios based on discrete time survival models. Note: The jitter represents a small addition/subtraction to the true values to enhance separation of the plotted values for visual clarity. Anthracycline therapy: any regimen containing anthracyclines Radiation therapy: any radiation therapy regardless of extent