Development and Validation of a Risk Model for Breast Cancer–Related Lymphedema
Authors: Jennifer Yin Yee Kwan, Petra Famiyeh, Jie Su, Wei Xu, Benjamin Yin Ming Kwan, Jennifer M. Jones, Eugene Chang, Kenneth W. Yip, Fei-Fei Liu
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Approximately 1 in 5 patients with breast cancer who undergo axillary lymph node dissection will develop lymphedema. To appropriately triage and monitor these patients for timely diagnosis and treatment, robust risk models are required. <h3>Objective</h3> To evaluate the prognostic value of mammographic breast density in estimating lymphedema severity. <h3>Design, Setting, and Participants</h3> This prognostic study collected data from July 16, 2018, to March 3, 2020, from the electronic health records of patients of the Cancer Rehabilitation and Survivorship Program at the Princess Margaret Cancer Centre in Toronto, Ontario, Canada. Participants included women who had completed curative treatment for a first diagnosis of breast cancer and who were referred to the program. Also included were a sample of patients in the general breast oncology population who were receiving follow-up care at the center during the same period but who were not referred to the program. All patients attended follow-up appointments at the Princess Margaret Cancer Centre from January 1, 2016, to May 1, 2018. The cohort was randomly split 2:1 to group patients into a training cohort and a validation cohort. <h3>Exposures</h3> Participant demographic and clinical characteristics included age, sex, body mass index (BMI), medical history, cancer characteristics, and cancer treatment. <h3>Main Outcomes and Measures</h3> Spearman correlation coefficient between measured and predicted volume of lymphedema was calculated. Area under the curve (AUC) values were generated for predicting the occurrence of at least mild lymphedema (volume, &gt;200 mL) and severe lymphedema (volume, &gt;500 mL) at the time of initial lymphedema diagnosis. <h3>Results</h3> A total of 373 female patients (median [interquartile range] age, 52.3 [45.9-60.1] years) were eligible for this analysis. Multivariate linear regression identified 3 patient factors (age, BMI, and mammographic breast density), 1 cancer factor (number of pathological lymph nodes), and 1 treatment factor (axillary lymph node dissection) as independent prognostic variables. In validation testing, Spearman correlation revealed a statistically significant moderate correlation (coefficient, 0.42; 95% CI, 0.26-0.56;<i>P</i> &lt; .001) between measured volume and predicted volume of lymphedema. The AUC values were 0.72 (95% CI, 0.60-0.83) for predicting the occurrence of mild lymphedema and 0.83 (95% CI, 0.74-0.93) for severe lymphedema. <h3>Conclusions and Relevance</h3> This prognostic study found that patients with low breast density appeared to be at a higher risk of developing severe lymphedema. The finding suggests that by combining breast density with established risk factors a multivariate linear regression model could be used to predict the development of lymphedema and provide volumetric estimates of lymphedema severity in patients with breast cancer.