From February 2001 to April 2010, the European Organization for Research and Treatment of Cancer (EORTC) conducted the AMAROS trial across 34 centers located in nine European countries. The study included a group of 4,806 women living with T1-2 primary breast cancer and no palpable axillary lymphadenopathy and investigated whether axillary radiation therapy (AxRT) presents a better treatment option for women than the standard practice-intraoperative lymph node pathology or axillary lymph node dissection (ALND).
The study cohort was randomized into two groups: 2,402 patients were treated with ALND and 2,404 received AxRT. After following up with the cohort at a median of 6.1 years, investigators found that, while both ALND and AxRT provided patients with excellent and comparable axillary control, AxRT was associated with significantly decreased morbidity rates, specifically in rates of lymphedema.
A recent study, presented at the 2023 American Society of Breast Surgeons Annual Meeting, expanded upon the research conducted during the AMAROS trial. The multi-institutional investigative team explored the efficacy of intraoperative pathology evaluation of sentinel lymph nodes (SLN) during mastectomy and its influence on treatment options for breast cancer patients. Utilizing the National Cancer Database (NCDB), researchers were able to identify 8,216 patients with tumors up to 5 centimeters and were thought to be clinically node-negative, meaning they did not demonstrate observable symptoms, and who had undergone mastectomy.
"We used the National Cancer Database, which is a publicly available registry that captures about 70 percent of the United States population, and they collect different variables, including the variables that we needed for the study, including who got an SLN biopsy, how many SLNs were involved, and what type of axillary treatment was done," said lead study author, Olga Kantor, MD, MS, Breast Surgical Oncologist at Brigham and Women's Hospital and Dana-Farber Cancer Center Institute, as well as Assistant Professor of Surgery at Harvard Medical School. "We were interested in understanding how much of an impact intraoperative pathology played on axillary management decisions."
From the NCDB data, Kantor's team discovered that intraoperative pathology was not performed in 5,159 or 62.8 percent of patient mastectomies. However, the remaining 3,057 women or 37.2 percent did receive intraoperative pathology. Overall, this assessment led to axillary management as observation in 2,730 patients (33.2%); 2,184 (26.6%) received ALND; 1,820 (22.2%) received AxRT; and 1,482 (18%) were treated with ALND and AxRT.
Receiving both ALND and AxRT could reflect overtreatment in many women that might otherwise have been treated with either ALND or AxRT alone per the results of the AMAROS trial. Investigators used chi-square testing to compare these statistics and a multivariable analysis was used to determine possible predictors of overtreatment with both ALND and AxRT.
The statistical analysis showed intraoperative pathology (and subsequent real-time axillary surgical decisions) was the strongest predictor of whether a breast cancer patient was overtreated or not. They found that 40.2 percent of patients were treated with both ALND and AxRT after receiving intraoperative pathology assessments. This is compared to a mere 4.9 percent of women who were treated with dissection and radiation therapy after receiving post-operative pathology testing. Similarly, only a small number of patients required a second surgery for ALND when pathology was considered after mastectomy.
"I think the main reason that surgeons perform intraoperative pathology is because we can avoid a second surgery if we think someone is going to need it by acting on the pathology results during surgery" Dr. Kantor explained. "There are definitely situations where there's just much more disease than we expected, or there is something discovered intraoperatively, during surgery, that makes us suspicious of lymph node disease, based on how things look or feel that ALND would be appropriate.
"However, in patients that are likely to be recommended for radiation therapy if found to have positive SLN, deferring the decisions to the final pathology results allows for input from the radiation oncology team about the recommendation for radiation therapy, so we can make the decision for additional axillary treatment in a multi-disciplinary fashion."
Surgery is understandably stressful for patients and it is crucial for surgeons and cancer care teams to find the best approach(es) to successfully treat disease, while also doing their best to maintain patients' quality of life and keep care costs down. As Kantor's team has shown, intraoperative therapy often leads to overtreatment.
One known consequence of ALND is lymphedema. This occurs in about 15 percent of women after dissection, and the chance of developing this condition can increase with radiation as an additional treatment. Lymphedema is a condition caused by fluid buildup that leads to swelling and discomfort in a woman's arm.
"I don't think this study is practice-changing, but it draws our attention to what's being done across the country and offers an alternative approach," Kantor said. "Our institution has set out some guidelines in which we wait until the final pathology results in patients that would likely be recommended radiation if found to have positive SLN so that we can make those decisions together with our radiation oncologists. I think it also draws attention to the fact that a lot of people are probably being over-treated because of patients having intraoperative pathology and will hopefully allow some institutions to reconsider their protocols."
Lindsey Nolen is a contributing writer.