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Low Breast Density May Be Associated With Severe Lymphedema for Patients With Breast Cancer

Lower limb lymphedema (left).

Patients with low mammographic breast density showed a higher risk of developing severe lymphedema during or after axillary lymph node dissection for breast cancer, according to a prognostic study published today in JAMA Network Open.

Among patients with breast cancer who undergo axillary lymph node dissection, approximately 20% experience secondary lymphedema, a condition in which damage to the lymphatic drainage causes swelling of skin and adipose tissue. "Lymphedema becomes increasingly challenging to treat over time because of the development of progressive fibrosis during late stages of this condition. Understanding who is at greatest risk of lymphedema will facilitate monitoring, earlier disease diagnosis, and early initiation of therapies to decrease disease morbidity," write the investigators, led by first author Jennifer Kwan, MD, of the Department of Radiation Oncology at the University of Toronto in Ontario, Canada. "Currently, most lymphedema risk models are based on cancer and treatment risk factors, yet these features do not fully account for the risk. Improved risk modeling that incorporates the underlying patient-specific biological drivers of this condition is required for a more accurate and personalized risk assessment."

The authors examined the electronic health records of 373 patients with breast cancer who were between 45.9 to 60.1 years of age. When forming each cohort, the authors considered patient age, sex, body mass index (BMI), medical history, cancer characteristics, and cancer treatment. The study measured Spearman correlation coefficients between measured and predicted volume of lymphedema. Area under the curve (AUC) values were generated for predicting the occurrence of at least mild lymphedema, with a volume >200 mL, and severe lymphedema, with a volume of >500 mL at the time of initial lymphedema diagnosis. Participants included patients who had completed curative treatment for a first diagnosis of breast cancer and patients with breast cancer undergoing follow-up care. Patients were placed into a training cohort and a validation cohort in a 2:1 ratio.

Using multivariate linear regression, data on patient age, BMI, and mammographic breast density were collected, along with number of pathological lymph nodes and axillary lymph node dissection. Validation testing revealed a statistically significant moderate correlation coefficient of 0.42 (P<0.001) between measured volume and predicted volume of lymphedema. The AUC values were 0.72 for predicting the occurrence of mild lymphedema and 0.83 for predicting 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," conclude the authors. "This study identified five readily available clinical factors, including patient, cancer, and treatment factors, that can be used to generate volumetric estimates of lymphedema severity in patients with breast cancer. To our knowledge, this study is the first to use mammographic breast density as an independent prognostic factor for lymphedema risk and to provide volumetric estimates of lymphedema morbidity. Predictions of lymphedema occurrence and morbidity can help triage patients for increased disease monitoring and thus allow for earlier diagnosis and optimal management of this condition. Such predictions also can assist in risk stratification in future clinical trials on novel therapeutic interventions for lymphedema."

For More Information

Kwan JY, Famiyeh P, Su J, et al (2020). Development and validation of a risk model for breast cancer–related lymphedema. JAMA Netw Open. [Epub ahead of print] DOI:10.1001/jamanetworkopen.2020.24373

Image credit: Abdullah Sarhan. Licensed under CC BY 4.0


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