1. Froelich, Warren

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Black women experience a 3.5-fold greater risk of developing lymphedema following axillary lymph node surgery than White women, according to a prospective multivariant analysis led by researchers at Memorial Sloan Kettering Cancer Center in New York.

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Lymphedema-a build-up of fluid under the arm, legs, or other extremities when the lymph system is damaged or blocked-is a feared complication of cancer treatment that can put patients at increased risk for infection, resulting in tissue death or sepsis.


Results of this study, presented during the 2021 San Antonio Breast Cancer Symposium (SABCS) held December 7-10, reveal that Black women are far more susceptible to this adverse side effect following the removal of lymph nodes under the arm, suggesting alternative approaches should be considered for this population.


"I think it's really important to stratify risk," said Andrea V. Barrio, MD, an associate attending physician in the breast service, Department of Surgery at Memorial Sloan Kettering Cancer Center, who presented findings during a SABCS press briefing. "Once we tailor that risk, we can start to identify which patients might benefit from preventive strategies."


Added Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio MD Anderson Cancer Center, and SABCS Co-Director/moderator: "We already know that African-American women have a higher risk of triple-negative cancer, which is one of the most aggressive breast cancers to treat. So I think it's important for us to recognize the symptoms early, and treat our patients preemptively so we can potentially prevent lymphedema in these patients."


As outlined during the press briefing, Barrio noted that epidemiologic studies and patient reports previously suggested an increased susceptibility of lymphedema in Black women compared to White women; however, prospective clinical data has been lacking.


The aim of this study was to assess the incidence of lymphedema in a prospective cohort of patients treated with axillary lymph node dissection, to identify risk factors with lymphedema development, and to evaluate the impact of race and ethnicity on lymphedema incidence and severity. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10 percent.


From November 2016 to March 2020, Barrio and colleagues enrolled 304 patients in their study who had an axillary lymph node dissection. Some 276 had at least one longitudinal measurement after baseline, as measured with a perometer-an instrument which uses a slide frame and infrared light sensor to measure arm volume-and this group made up the cohort for this study. Measurements were taken at baseline, postoperatively, and every 6 months for a total of 2 years.


Patients enrolled in the cohort had a median age of 48 years and median baseline BMI of 26.4. About 60 percent of these patients were White, 20 percent Black, 11 percent Asian, and 6 percent Hispanic. Some 68 percent were identified as hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancers. About 70 percent received neoadjuvant chemotherapy while the remainder underwent upfront surgery. Of those having upfront surgery, the majority received adjuvant chemotherapy, with 94 percent of this group receiving a taxane-containing regimen, 95 percent receiving radiotherapy, and 93 percent receiving nodal radiotherapy. The median number of lymph nodes removed was 18 with a median number of two positive lymph nodes.


Barrio and colleagues then stratified the clinical characteristics of the study cohort by race and ethnicity. White and Black women were older; Black and Hispanic women had a higher BMI; Black women were more likely to present with CN1 disease and Hispanic women with CN2 and CN3 disease. Black and Hispanic women were more likely to undergo breast-conserving surgery with Hispanic women having higher number of lymph nodes removed, and Black and Hispanic women more likely to receive nodal radiotherapy.


At the median follow-up of 22.6 months, some 56 women developed lymphedema and at 24 months the lymphedema rate was 24.7 percent. Results showed that the incidence of lymphedema varied significantly by race and ethnicity. The highest incidence of lymphedema at 24 months was observed in Black women at 39 percent compared to 28 percent in Hispanic women, 23 percent in Asian women, and 21 percent in White women.


The incidence of lymphedema also varied significantly by treatment group with a significantly higher incidence of lymphedema among those women receiving neoadjuvant chemotherapy with a 24-month rate of 31 percent compared to 11 percent in those undergoing upfront surgery.


A multivariant analysis concluded that Black women had a 3.5-fold increased risk of lymphedema compared to White women. Hispanic women also had a three-fold increased incidence of lymphedema compared to white women, though the number of Hispanic women in the study was small so confirmation is needed in a larger study, Barrio said.


Neoadjuvant chemotherapy significantly increased lymphedema compared to adjuvant chemotherapy in women undergoing axillary lymph node dissection and radiotherapy. Older age and increasing time from surgery were also modestly associated with a higher risk of lymphedema. Among patients were lymphedema, there was no difference in disease severity across racial and ethic groups, with similar relative volume changes observed.


"We postulate that neoadjuvant chemotherapy may cause fibrosis of tumor-filled lymphatics as well as lymphatic endothelial damage prior to surgery resulting in higher lymphedema incidence observed in our study," Barrio said. "In patient subsets unlikely to achieve a nodal pathological complete response with neoadjuvant chemotherapy, alternatives to avoid axillary lymph node dissection are needed."


Barrio noted that future research should address the biologic mechanisms behind the racial disparities in lymphedema observed in this study. In response to a question during the press briefing, Barrio said physicians, in the interim, should strive to do two things differently.


"One, I think with the use of really good systemic chemotherapy which, thank goodness we have, surgical de-escalation is the rule," she said. "And we need to just find ways to avoid doing axillary lymph node dissection. I think at some point this will become a relatively obsolete operation once we recognize that we can manage this axilla in other ways.


"But until then, we can also think about methods for immediate lymphatic reconstruction. We're doing a clinical trial looking at that now."


Warren Froelich is a contributing writer.