Approximately 150,000 women world-wide develop lymphedema after breast cancer treatment each year. However it is difficult to predict which women are at highest risk. Now, researchers at Hospital Sirio Libanes in Sao Paulo, Brazil and the Cleveland Clinic have built models that can be used to calculate an individual patient's absolute risk of developing lymphedema with 70% accuracy. The data were presented during a news conference for the 2011 Breast Cancer Symposium.
“This work comes at a time of transition in the management of axilla,” said Andrew Seidman, MD, a breast cancer specialist at Memorial Sloan-Kettering Cancer Center and a member of the American Society of Clinical Oncology Cancer Communications Committee, who moderated the news conference. “We certainly are living in the sentinel node biopsy era, when fewer women undergo full axillary dissection than decades ago. This has resulted in the decline of lymphedema. But for patients with extensive axillary involvement there still remains the need for more complete axillary dissection, and also the consideration of regional node irradiation.
“So the ability to preoperatively or postoperatively identify patients who are at a particularly high risk of developing lymphedema is an important step forward. It allows us to identify patients who then can be appropriately triaged for early intervention or perhaps for clinical trials aimed at preventing what some people consider inevitable, the development of lymphedema.”
The researchers for the study (Abstract 8), led by Jose Bevilacqua, MD, PhD, a surgical oncologist at Hospital Sirio Libanes, studied a prospective cohort of 1,243 women with the specific aim of determining the incidence and predictive factors associated with lymphedema, which is defined as a 200 cc or greater difference in ipsilateral and contralateral arm volumes. All of the women had undergone breast-conserving surgery or mastectomy and axillary lymph node dissection at the Brazilian National Cancer Institute between August 2001 and November 2002.
The five-year incidence of lymphedema was 30.3% in the cohort. Dr. Bevilacqua and colleagues found that age, body mass index (BMI), number of cycles of neoadjuvant chemotherapy, number of cycles of adjuvant chemotherapy, level of axillary lymph node dissection, radiotherapy field, seroma, and early edema were each independently predictive of lymphedema.
“One of the novel findings of our study is that ipsilateral neoadjuvant chemotherapy infusion is as morbid as adjuvant chemotherapy infusion to increase the risk of lymphedema,” said Dr. Bevilacqua. “This is somewhat intuitive, but it has never been described, and the great majority of clinical oncologists are not aware of the fact.”
Using these predictive factors, the team generated three nomograms to predict an individual woman's risk preoperatively, within the first six months after surgery, and six or more months beyond therapy.
In the preoperative model, the factors included in the model are age, BMI, number of cycles of neoadjuvant chemotherapy. For the first six months post-surgery, the model includes those variables and adds level of axillary node dissection and radiation therapy field. The third model includes the previous variables, as well as the development of seroma and early edema. The concordance for each of the models with actual occurrence was 0.706, 0.729, and 0.736 for the preoperative, early post-surgery, and late post-surgery models, respectively.
Tool to Measure Arm Volume
To facilitate the use of nomograms, the team has also developed a tool for standardized measurement of the arms, which can be found at www.armvolume.com (click on “I Agree” choice at the bottom to get to the actual site). After publication of their manuscript, the team will make their nomograms for lymphedema risk available at www.lymphedemarisk.com (same situation, to click through).
“Our analysis suggest that the nomograms are accurate to estimate the risk of lymphedema,” Dr. Bevilacqua said. He noted that there are currently more than 20 trials listed at clinicaltrials.gov that aim to develop new tools or treatments for lymphedema. The nomograms may help select patients for early intervention or referral to such trials, he said.
Dr. Seidman echoed those comments, saying that if one can identify patients at high risk, researchers may be able to develop early intervention that works. “What this nomogram does is allow us, in a scientific way, to segregate patients in terms of their risk so that we can have more uniform cohorts so early interventions can be more rigorously studied.”