Lymphedema Related to BMI, Higher Stage, and Genes

A news release from the University of California School of Nursing

The risks of developing lymphedema increased significantly for women who had more advanced breast cancer at the time of diagnosis, more lymph nodes removed or a significantly higher body mass index, and a specific set of genes, according to a study of some 400 women who were tracked over four to five years and published online on April 16, 2013 in PLOS ONE.

The study is the first to evaluate genetic predictors of lymphedema in a large group of women using a type of technology, bioimpedance spectroscopy, to measure increases in fluid in the arm. Bioimpedance spectroscopy is a noninvasive procedure that allows one to measure body composition including an increase in fluid in an arm or a leg.

“The genetic markers found in our study make perfect sense,” said senior author Bradley Aouizerat, PhD, a professor at the UCSF School of Nursing in the department of physiological nursing. “These genes are ‘turned on’ later in the development of our lymph system and blood vessels. They appear to play a role in the ability of our lymphatic system to function on an ongoing basis. It is possible in some individuals who have changes in these genes, that lymphedema could develop after an injury like breast cancer surgery because these genes do not function properly.” 

Lymphedema is a swelling or buildup of fluid in the lymphatic tissues, typically in the arms and fingers but also commonly in the patient’s legs and trunk. It can occur after treatment for any form of cancer that affects lymph node drainage. The exact prevalence is unknown, and the onset of the condition can greatly vary, but as many as 56 percent of women who undergo breast cancer surgery develop lymphedema within two years, according to the National Cancer Institute. More than half a million breast cancer survivors in the United States are estimated to be afflicted with the condition.

Lymphedema can be debilitating, causing scarring, discomfort, disfigurement, difficulty in exercising, walking or other daily activities. Some patients are unable to wear their usual clothing or jewelry because of the increased weight and size of their affected limbs. There’s no cure for the condition – treatment generally centers on controlling pain and reducing swelling.

To date, much of the research on lymphedema focused on identifying which women were at greater risk for the development of the condition, and relied only on patient self-reporting or on data from their medical charts.

In the new study, the authors hypothesized that genomic determinants were behind some of the variations in the occurrence of lymphedema as well as the time of onset of the condition.
The study involved 410 women who were at least six months post-treatment for breast cancer surgery on one breast, and either had lymphedema in their upper extremity or did not have the condition.

The women were assessed at the Clinical Research Center at the University of California at San Francisco Medical Center at Mt. Zion, one of eight clinical sites in the Bay Area managed by UCSF’s Clinical and Translational Science Institute.

As part of the research, the women underwent spectroscopy measurements of their arms and genomic DNA was extracted. Genotyping was performed blinded to the women’s lymphedema status.

The researchers found that women with lymphedema had:

• More advanced breast cancer at the time of diagnosis;
• A higher number of positive lymph nodes;
• Were more likely to have a significantly higher body mass index.

The authors also found associations between lymphedema and genes known to play a role in the development of lymphedema—FOXC2 haplotype
A03, LCP2 rs315721, NRP2 rs849530, NRP2 haplotype F01,
SYK rs158689, VCAM1 rs3176861, and VEGFC haplotype B03

“These findings suggest that complex interactions may exist between a variety of patient characteristics and genetic markers that place some women at higher risk for the development of lymphedema,’’ said lead author Christine Miaskowski, RN, PhD, a professor at the UCSF School of Nursing in the department of physiological nursing. “Our hope is that once our findings are confirmed in a future study, we will be able to identify women at higher risk for lymphedema prior to breast cancer surgery, and initiate measures to prevent the development of this devastating condition.”