“Axillary lymph node dissection remains the main risk factor for the development of lymphedema,” Andrea Barrio, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, New York, said at a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.
“We observed a higher incidence of lymphedema in Black women treated with ALND and RT [radiotherapy] after adjustment for other variables,” Dr. Barrio added. “While the etiology for this increased incidence is largely unknown, future studies should address the biologic mechanisms behind racial disparities in lymphedema development.”
Dr. Barrio and colleagues included 276 patients in the analysis – 60% were White, 20% Black, 11% Asian, and 6% Hispanic. The remaining 3% did not report race or ethnicity. Patients’ median age at baseline was 48 years, and the median body mass index was 26.4 kg/m2. Slightly over-two thirds of participants had hormone receptor (HR)–positive/HER2-negative breast cancer.
All patients underwent unilateral ALND. About 70% received neoadjuvant chemotherapy (NAC), and the remainder had upfront surgery followed by adjuvant chemotherapy. Ninety-five percent of patients received radiotherapy, and almost all underwent nodal radiotherapy as well.
The median number of lymph nodes removed was 18, and the median number of positive lymph nodes was two. Using a perometer, arm volume was measured at baseline, postoperatively, and every 6 months for a total of 2 years. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10% from baseline.
At 24 months, almost 25% of the group had lymphedema, but the incidence differed significantly by race and ethnicity. The highest incidence was observed among Black women, at 39.4%, compared to 27.7% of Hispanic women, 23.4% of Asian women, and 20.5% of White women in the study.
The incidence of lymphedema also varied significantly by treatment group. The incidence was twofold greater among women treated with NAC in comparison with those who underwent upfront surgery (30.9% vs. 11.1%), Dr. Barrio noted.
On multivariate analysis, Black race was the strongest predictor of lymphedema. Compared to White women, Black women had a 3.5-fold greater risk of lymphedema. Hispanic women also had a threefold increased risk compared to White women, but Dr. Barrio cautioned that there were only 16 Hispanic patients in the study.
Older age and increasing time from surgery were also both modestly associated with an increased risk of lymphedema. Among women who ultimately developed lymphedema, “severity did not vary across race or ethnicity with similar relative volume changes observed,” Dr. Barrio said.
Given that the study found that NAC was an independent predictor of lymphedema, should alternatives to NAC be favored?
Although oncologists provide NAC for a variety of reasons, women with HR-positive/HER2-negative disease – which represent the majority of patients in the current analysis – are most likely to have residual disease after NAC, Dr. Barrio noted. This suggests that oncologists need to start looking at surgical de-escalation trials in this group of patients to help them avoid ALND.
Asked whether oncologists still underestimate the impact that lymphedema has on patients’ quality of life, Virginia Kaklamani, MD, professor of medicine, UT Health San Antonio MD Anderson Cancer Center, Texas, said the oncology community has come a long way.
“Any surgeon or medical oncologist will tell you that in the 1960s and 70s, women were having much higher rates of lymphedema than they are now, so this is something that we do recognize and we are a lot more careful about,” she told this news organization.
Surgical techniques are also better now, and the number of lymph nodes that are being removed is much reduced. Nevertheless, when physicians add ALND and radiation to the axilla, “rates of lymphedema go up,” Dr. Kaklamani acknowledged. “We need these women to have physical therapy before they develop lymphedema.”
Dr. Barrio agreed, adding that if oncologists could identify earlier thresholds for lymphedema, before patients develop arm swelling, “we may be able to intervene and see a reduction in its development.”
In the meantime, Dr. Barrio and colleagues are testing the protective value of offering immediate lymphatic reconstruction following ALND versus no reconstruction. In addition, they will be studying banked tissue from Black women to better understand any racial differences in inflammatory responses, the risk of fibrosis, and the reaction to radiotherapy.
“I think we see that inflammation is a key driver of lymphedema development, and so maybe Black women are predisposed to a different inflammatory reaction to treatment or perhaps have higher levels of inflammation at baseline,” Dr. Barrio speculated.
“I think it’s also important to stratify a woman’s risk for lymphedema, and once we can tailor that risk, we can start to identify which patients might benefit from preventative strategies,” she added.
Dr. Barrio has disclosed no relevant financial relationships. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics and as a speaker for Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, Novartis, AstraZeneca, Daiichi Sankyo, and Seattle Genetics. She has also received research funding from Eisai.
A version of this article first appeared on Medscape.com.