Patients with breast cancer may be able to avoid lymphedema, which can occur after surgery to remove lymph nodes in the axilla, by having radiotherapy instead.
New findings, presented at the 15th European Breast Cancer Conference (EBCC15) in Barcelona, suggest that axillary radiotherapy may be as effective at killing any remaining cancer cells, while being less likely to trigger lymphedema, an often painful swelling of the arm and armpit (Abstract 7).
These results come from the pilot phase of the phase III ADARNAT randomized international clinical trial, which is investigating whether axillary radiotherapy (ART) has a lower risk of lymphedema than axillary lymph node dissection (ALND) in patients with breast cancer who have received neoadjuvant systemic therapy, such as chemotherapy or hormone therapy, before surgery, and in whom cancer has spread to only one or two lymph nodes. The trial will also be looking at overall survival and disease-free survival.
ART vs ALND
At EBCC15, the researchers stressed that these are preliminary results from 2 years of follow-up in the pilot study, and that clinicians should wait for the results from the phase III part of the trial, which is ongoing, before considering changing clinical practice.
Amparo Garcia-Tejedor, MD, PhD, of the Functional Breast Unit at Bellvitge University Hospital, Spain, and the Institut Català d’Oncologia, is leading the trial. She told the conference attendees that studies had already shown that ART was a good alternative to ALND in patients for whom the first line of treatment was surgery.
“In situations where patients have received chemotherapy or hormone therapy before surgery, it is expected that results could be similar,” she said. “However, robust prospective data are not yet fully established or published.”
“Many patients treated with neoadjuvant therapy experience a significant reduction in axillary disease burden and ultimately present with only one or two lymph nodes that are positive for cancer metastases, which often correspond to the sentinel lymph node, while the remaining axillary nodes are negative. This observation strongly suggested that further axillary surgery might be unnecessary in a substantial proportion of patients and that a strategy of de-escalation should be explored,” she concluded.
ADARNAT
From June 2021 to April 2023, the ADARNAT trial recruited 272 patients with breast cancer which might have metastasized to one or more lymph nodes. The patients had received neoadjuvant therapy and, at the time of surgery, had metastatic cancer in one or two sentinel lymph nodes. The patients were randomly assigned to receive either ART or ALND; patients in both arms of the trial also received radiotherapy to areas of the breast and chest. Results were available for 46 patients in the ART group and 56 patients in the ALND group, with a median follow-up period of 2 years.
No cancer recurred in the axillary area in the ART group and one patient experienced recurrence in the ALND group (1.8%). Cancer metastasized to other parts of the body in 4.4% vs 5.5% of the patients, respectively, and there were two deaths in the ALND group (4.3%). Lymphedema occurred more frequently after ALND (26.7%) than ART (18.9%), although this was not statistically significant. Disease-free and overall survival rates were similar after 2 years of follow-up.
Dr. Garcia-Tejedor said, “These results indicate that ART instead of ALND is feasible and has good cancer outcomes at 2 years. While some specialists have already begun to substitute ALND with ART without waiting for definitive results, the only way to determine with certainty whether this strategy is truly safe and effective is through participation in a well-designed clinical trial—such as the one we are now conducting. This is particularly important given that the study population includes patients with residual axillary disease and, therefore, a potentially worse prognosis. In this context, treatment decisions should not be made without robust evidence. Our trial is designed to provide the necessary data to definitively answer this question and to ensure that any future change in standard practice is safe in terms of cancer outcomes and is also beneficial for patients.”
Toxicities
Maria Laplana-Torres, MD, PhD, a radiation oncologist at the Hospital Clínic de Barcelona, Spain. She presented results from the pilot phase of the trial that showed that although ART was associated with more damage to the skin from radiation, this tended to be transient and easily treatable (Abstract 28).
Acute skin damage (grade 2 or above) occurred in 27.8% of ART patients compared with 13.3% after ALND. It consisted mainly of skin redness, pigment changes, or skin peeling in some cases. There were no significant differences in later skin damage between the two groups.
Dr. Laplana-Torres commented, “Some patients experienced mild, temporary difficulty raising the arm above the shoulder or lifting it to the side. These limitations were usually short-lived and did not affect everyday activities. We found that treating the axilla with radiotherapy instead of extensive surgery can avoid a more aggressive operation without compromising treatment safety in patients with sentinel lymph node involvement. One and 2 years after treatment, there were no meaningful differences in arm mobility or quality of life between the two groups, although there was a more favorable trend in the ART patients. These results show that axillary radiotherapy may be a safe and less invasive option for some women treated with chemotherapy or hormone therapy before surgery. This kind of research is essential to continue improving patient outcomes and to define safer, equally effective therapeutic approaches.”
Ongoing Research
So far, more than 500 patients have joined the main phase III clinical trial. The researchers estimate that approximately 3 more years will be required to complete patient recruitment. This will then be followed by the planned 5 years of follow-up to fully assess cancer outcomes.
Dr. Garcia-Tejedor concluded, “If the study confirms the safety and effectiveness of axillary treatment de-escalation, the implications for both patients and clinicians could be substantial. For patients, the main potential benefit would be an improvement in quality of life, particularly through a reduction in lymphedema and other functional complications associated with axillary surgery. For clinicians, these findings would support a paradigm shift in axillary management, reinforcing the move away from routine extensive surgery toward more personalized and less morbid treatment strategies, while maintaining good cancer outcomes.”
DISCLOSURE: For full disclosures of the study authors, visit m.eortc.org/cmPortal/Searchable/ebcc15.
