In a study from the Mayo Clinic, Rochester, Minnesota, the risk of lymphedema in a population-based breast cancer cohort was related to multimodality therapy and not axillary surgery alone, investigators reported at the American Society of Breast Surgeons (ASBrS) Annual Meeting.1
“Most patients fear they are going to get lymphedema if they have an axillary dissection and want to avoid that. Axillary dissection does produce higher rates [of lymphedema] than sentinel node surgery, but it’s not the sole factor,” said lead author Judy C. Boughey, MD, Professor of Surgery and Vice Chair of Research at the Mayo Clinic. “With every additional insult to the axilla, the risk of lymphedema increases.”
“Obviously, one thing we can do is minimize our treatments, especially with less-invasive surgical approaches,” she continued. “But it’s important for patients to realize that avoidance of axillary dissection does not necessarily get them off the hook.”
Toan T. Nguyen, MD, a fellow in breast surgical oncology who presented the findings at the ASBrS Meeting, reported on a chart review, enhanced with electronic natural language processing, of 1,794 patients (median age, 60 years) diagnosed with a first breast cancer in Olmsted County, Minnesota, between 1990 and 2010. Most patients (48%) were diagnosed at stage I, with 17% diagnosed at stage 0; 29% diagnosed at stage II; and 6% diagnosed at stage III. For 44% of patients, staging was by axillary lymph node dissection, and for 40%, it was with sentinel lymph node surgery. A total of 16% had no axillary surgery. More than half (57%) received radiation, and 29% received chemotherapy. Outpatient and inpatient records from all clinical encounters, irrespective of site and discipline, were reviewed from index.
After a median follow-up of 10 years, 209 patients had been diagnosed with breast cancer–related lymphedema, mostly within 5 years of surgery. The incidence of lymphedema increased over time, from 6.9% at 2 years to 9.1% at 5 years to 11.4% at 10 years. No cases of lymphedema were observed among the 282 women who did not undergo any axillary surgery.
Factors Influencing Lymphedema
The investigators found no significant difference in the rate of lymphedema based on the type of breast cancer surgery (mastectomy vs breast-conserving surgery). Although lymphedema did occur significantly more often in patients who had axillary lymph node dissection (15.9%) than in those who had sentinel lymph node surgery (5.3%; P < .001), in a subset of 453 patients who did not receive radiation or chemotherapy, lymphedema rates were similar for axillary lymph node dissection (3.5%) and sentinel lymph node surgery (4.1%).
Radiotherapy and chemotherapy were both considerable factors. By 5 years, almost one-third (31.3%) of patients who had nodal irradiation, with or without breast or chest wall irradiation, developed lymphedema, as compared with 5.9% of patients who did not receive radiation (P < .001). Similarly, lymphedema was present in 27.2% of patients who received anthracycline/cyclophosphamide (AC) plus a taxane, 29.7% of those who received a taxane without AC, and 6.0% of those who received no chemotherapy (P < .001).
“We are not sure why risk is increased especially for taxanes, but it’s possibly related to mechanism of action,” Dr. Boughey said.
The incidence of lymphedema also increased significantly as body mass index increased. Patients with a body mass index < 25 kg/m2 had an 8.0% risk at 5 years, whereas those with a body mass index > 35 kg/m2 had a 17.1% risk.
The highest rates of lymphedema occurred in women with more advanced disease treated with multimodality therapy. Although increasing disease stage was a risk factor on the univariate analysis, it failed to be significant in the multivariate analysis, where the primary factors were the type of axillary lymph node dissection, use of radiation (particularly to the nodes), use of chemotherapy (particularly taxanes), and high body mass index.
The multivariable analysis determined these hazard ratios (HR) for several independent predictors of lymphedema:
International Panel Weighs In
Sarah McLaughlin, MD, Associate Professor of Surgery at the Mayo Clinic in Jacksonville, chaired an international multidisciplinary panel that addressed the topic during a special session at the ASBrS Meeting. The goals of the panel were to acknowledge lymphedema as an issue affecting many breast cancer survivors and as one that is a long-term problem for which long-term surveillance is necessary, she told The ASCO Post.Error loading Partial View script (file: ~/Views/MacroPartials/TAP Article Portrait and Quote.cshtml)
“The panel agreed there is a paradigm shift toward early surveillance with routine follow-up. Thus, we have the opportunity for early intervention, which appears to allow for the most effective treatment strategies for patients,” said Dr. McLaughlin. “The panel feels strongly that lymphedema is a chronic sequela for which multidisciplinary care is optimal, including the early involvement of lymphedema treatment specialists and even highly specialized microvascular surgeons in select cases/teams. The best care for lymphedema patients is provided with a team approach.”
Awareness Among Medical Oncologists
Dr. Boughey believes most oncologists are unaware of the “multimodal insult” that results in lymphedema. “I do think it’s underrecognized,” she told The ASCO Post. “Most patients have heard of lymphedema and discuss it with their surgeons. I think most radiation oncologists realize radiation is also associated with risk. But I’m not sure many medical oncologists include lymphedema risk when they discuss side effects of treatment,” she said.
Dr. Boughey advocated an individualized risk-stratified survivorship approach. Patients at the highest risk—exceeding 40%—are generally those undergoing axillary lymph node dissection, nodal radiation, and AC/taxane chemotherapy. Mid-level risk—approximately 25%—is conferred by axillary lymph node dissection and nodal radiotherapy. Patients at the lowest risk are those who have axillary surgery alone, especially sentinel lymph node surgery.
“If you are in the highest-risk group, you probably have aggressive disease and need all these treatment modalities,” commented Dr. Boughey. “These patients should have their arms evaluated early on and be evaluated in a lymphedema clinic. Early detection and treatment are key. Patients should not wait until they see their arm swelling.” ■
Disclosure: Drs. Boughey and McLaughlin reported no conflicts of interest.
1. Nguyen T, Hoskin T, Habermann E, et al: Breast cancer-related lymphedema risk is related to multidisciplinary treatment and not surgery alone: Results from a large cohort study. 2017 American Society of Breast Surgeons Annual Meeting. Abstract 257052.
Michael Berry, MD, a breast surgeon who is Director of the Margaret West Comprehensive Breast Center at The West Cancer Center, Memphis, told the The ASCO Post that these findings “echo what surgeons already know,” which is that lymphedema is a result of multiple insults to the axilla. But one...