Lymphedema and Breast Cancer: When Is Risk Greatest?

The time course for developing lymphedema depends on the type of breast cancer treatment, but the risk peaks between 24 and 36 months post therapy, regardless of treatment type, according to new research. Receipt of radiation therapy (RT) is also a key to the timing. "Lymphedema develops earlier in patients who receive radiation, especially those receiving regional lymph node radiation," said the study's lead author, Susan McDuff, MD, PhD, a resident in radiation oncology at the Massachusetts General Hospital (MGH) Cancer Center in Boston.

Lymphedema can be "an incredibly morbid" complication following treatment for breast cancer and is an ongoing source of anxiety for survivors, she said here at the American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting. To help patients know when they may be "out of the woods," Dr McDuff and colleagues undertook a cohort study to determine whether there is a period when patients are at greatest risk. First, they looked at cumulative incidence.

The team analyzed the records of 1495 patients seen between 2005 and 2016 in a prospective lymphedema screening program at MGH. The time it took to reach 5% cumulative incidence by treatment group was 32 months for surgery alone and 15 months for RT (P = .02) However, a further look at the data revealed that patients who received regional lymph node radiation (RLNR) reached the 5% cumulative incidence in only 6 months vs 37 months for those who received local RT (P < .0001). There was a median follow-up of 3.9 years and a cumulative lymphedema incidence of 11.4% in the study population. Nearly three quarters (73%) of the patients received RT as a component of their treatment. To pinpoint risk over time, the researchers looked at the percentage of patients in various treatment groups who were diagnosed with lymphedema in each year during the first 5 years post therapy. This was done by plotting the annual hazard rate for the treatment groups. All patients received some mix of axillary surgery and RT.

The groups were as follows: no axillary surgery (n = 180); sentinel lymph node biopsy (SLNB) plus or minus local RT (n = 899); SLNB plus regional lymph node radiation (RLNR) (n = 46); and axillary lymph node dissection (ALND) plus or minus local RT (n = 132); and ALND plus RLNR (n = 264). "The timing of the risk appears to be the most significant within the first 2 to 3 years after treatment," summarized Dr McDuff.


The new study addresses an important clinical question, said Abram Recht, MD, professor of radiation oncology at Harvard Medical School in Boston, who acted as an adviser to the study authors. "If you are going to do surveillance, how long do you have to do it?" he commented to Medscape Medical News. "You can expect that most patients who undergo sentinel lymph node biopsy with or without local RT, which is the largest treatment group, may not need active monitoring past 2 years," he concluded. "The period of the greatest risk is the first 3 years," said Dr Recht, echoing Dr McDuff. "If lymphedema hasn't developed by 5 years, then it probably won't happen," he added. The new results are an argument for "personalizing" a lymphedema monitoring program, said Dr McDuff, adding that more follow-up is needed for high-risk groups.

The goal is early identification and intervention. Shannon MacDonald, MD, associate professor of radiation oncology at Harvard, who acted as discussant of the study, said that the hope with monitoring is "that an earlier intervention for lymphedema would improve outcome." Dr MacDonald told Medscape Medical News that the new study results will also "allow patients to have some alleviation of anxiety as to when to expect lymphedema if it occurs," she said. The findings could also influence "when clinicians have patients come in for monitoring," Dr MacDonald added. This "very large" study makes a "meaningful contribution" to clinical knowledge, in part because there are "limited" data on timing, she said. Lymphedema is less common than in the past, owing to improvements in surgical management, but inaccuracy of measurements has plagued estimates of the incidence of lymphedema, Dr MacDonald said.

The new MGH study used a perometer, a tool that employs infrared technology to objectively measure the limb, which is "more likely to be accurate than a tape measure or other modalities," she said. The perometer was used to perform prospective arm volume measurements of the study patients preoperatively and then postoperatively and in follow-ups at regular intervals. Lymphedema was defined as a >10% relative volume increase occurring >3 months postoperatively. The treatments for lymphedema in the cohort included compression sleeves (88%), manual decompression (52%), and physical therapy–directed exercise (89%). "Patients worry a lot about lymphedema" concluded Dr Recht. "It's a really hard thing in survivorship," agreed Dr McDuff.