Lymphedema Risk in Breast Ca Linked to NAC Duration

In women with node-positive breast cancer, secondary lymphedema was associated with the duration of neoadjuvant chemotherapy (NAC), the extent of axillary dissection, and obesity, researchers found.

Analysis of data after NAC and before surgical intervention in a cohort of 486 women with cT0-T4N1-2M0 breast cancer with axillary nodal metastasis at diagnosis showed that NAC for at least 144 days (hazard ratio [HR] 1.79) was associated with an arm volume increase of 20% (V20) or more, reported Jane M. Armer, PhD, RN, of the Ellis Fischel Cancer Center, Sinclair School of Nursing, at the University of Missouri in Columbia, and colleagues. Each additional day of NAC was associated with increased risk of lymphedema.

“This is particularly pertinent information to be further explored in future studies, as many of the current protocols involve neoadjuvant chemotherapy,” Armer told MedPage Today.

The analysis, published online in JAMA Surgery, also demonstrated that a body mass index (BMI) of 30 or greater was associated with symptoms of secondary lymphedema (HR 1.56, 95% CI 1.12-2.17), including patient-reported arm heaviness or swelling. Risk of lymphedema increased 4% with each point of increase in BMI.

With a median follow-up of 2.2 to 3.0 years, an arm volume increase of at least 10% (V10) was highest in patients who underwent removal of 30 or more nodes (HR 1.70), and increased with the number of positive nodes removed (HR 1.03 per node).

“In addition to recommended general surveillance for breast cancer survivors at risk for lymphedema, clinicians have an opportunity to initiate individualized surveillance programs for patients with longer neoadjuvant chemotherapy regimens and higher body mass index to allow early detection and intervention for lymphedema,” Armer said.

The analysis is a substudy of the women with lymphedema enrolled in the American College of Surgeons Oncology Group Alliance for Clinical Trials in Oncology Z1071 trial. It is also part of the ongoing Alliance A011202 trial, which is evaluating the need for axillary lymph node dissection (ALND) in patients with a positive sentinel lymph node (SLN) after NAC. Outcomes will be compared with those of ALND with axillary radiotherapy.

The researchers noted that despite changes to axillary management in favor of SLN surgery, recent data demonstrate that up to 30% of breast cancer survivors still develop lymphedema.

In the current substudy, all women with lymphedema underwent axillary dissection, 87% received postoperative radiotherapy, and 46% had a BMI of 30 or more. Mean patient age was 50, and data analysis took place from January to November 2018. Lymphedema symptoms were defined as patient-reported arm heaviness or swelling or an arm volume increase of V10 or V20.

At 3 years, the use of volumetric measurements or a validated questionnaire confirmed that the cumulative incidence for symptoms of lymphedema was 37.8%. A total of 58.4% of patients had V10 and 36.9% had V20.

Adjuvant radiotherapy, which was administered to 416 patients (87.0%), was not associated with the incidence of lymphedema, the analysis showed, although this result may be limited by the small number of patients who did not receive radiotherapy, Armer and co-authors said.

In addition, lymphedema was not associated with the type of chemotherapy regimen, whether it contained anthracyclines or taxanes or both. Neither was an association observed between lymphedema risk and type of surgery — either lumpectomy or mastectomy — or with patient age.

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