It may be possible for some patients with breast cancer to avoid adjuvant regional nodal irradiation safely, according to the results of the NRG Oncology/NSABP B-51/RTOG 1304 clinical trial presented at the 2023 San Antonio Breast Cancer Symposium.1 These findings particularly apply to patients whose breast cancer converted from lymph node–positive to lymph node–negative after neoadjuvant chemotherapy. There was no difference in the 5-year rates of disease recurrence or death among patients who had regional nodal irradiation and those who did not.
The 5-year rates of invasive breast cancer recurrence–free interval were 92.7% for those treated with regional nodal irradiation and 91.8% for those who underwent observation alone. Both groups of patients also had similar rates of locoregional recurrence–free interval, distant recurrence–free interval, disease-free survival, and overall survival.
“There is an active debate on whether these patients should be treated as patients with lymph node–positive disease, as per their original diagnosis, or as patients with lymph node–negative disease, which is how they present at the time of surgery,” said lead author Eleftherios (Terry) P. Mamounas, MD, MPH, FACS, Chair of the NRG Oncology Breast Committee; Professor of Surgery at the University of Central Florida; and Medical Director of the Comprehensive Breast Program at the Orlando Health Cancer Institute.
Regional nodal irradiation is used to reduce the risk of disease recurrence after surgery. Treatment for patients with node-positive disease includes chest wall irradiation plus regional nodal irradiation after mastectomy or the same treatment after breast-conserving surgery. However, patients with node-negative disease may be eligible for omission of regional nodal irradiation after surgery.
Regional nodal irradiation is associated with complications such as pain, fatigue, and lymphedema and may have an impact on future breast reconstruction. “Some patients may prefer to skip regional nodal irradiation to avoid these complications, and it is important to determine whether this treatment can be safely omitted in this patient population,” Dr. Mamounas said.
At our institution, we will be omitting regional nodal irradiation in most patients who meet the criteria for this study.— Eleftherios (Terry) P. Mamounas, MD, MPH, FACS
Tweet this quote
“For patients who have had mastectomy and are undergoing breast reconstruction, it will be a significant benefit to avoid radiation,” he added. “At our institution, we will be omitting regional nodal irradiation in most patients who meet the criteria for this study,” he told listeners.
Study Details
Patients enrolled in the trial had axillary node–positive disease at study entry and received neoadjuvant chemotherapy for at least 8 weeks plus anti-HER2 therapy if indicated. If they had pathologically node-negative disease at the time of surgery by axillary lymph node dissection or sentinel lymph node biopsy, they were randomly assigned 1:1 to receive (1) observation after mastectomy or whole-breast irradiation after breast-conserving surgery (no regional nodal irradiation arm); or (2) chest wall irradiation plus regional nodal irradiation after mastectomy or whole-breast irradiation plus regional nodal irradiation after breast-conserving surgery (regional nodal irradiation arm). Stratification factors included the type of surgery, hormone receptor status, HER2 status, adjuvant chemotherapy receipt, and achievement of breast pathologic complete response.
The trial enrolled 1,641 patients diagnosed with stage T1–T3 lymph node–positive, nonmetastatic breast cancer whose lymph nodes were judged to be cancer-free after at least 8 weeks of neoadjuvant chemotherapy and who went on to be treated with mastectomy or breast-conserving surgery. About 20% were stage T1, 60% were stage T2, and 20% were stage T3. Lumpectomy was performed in 58%, and mastectomy, in 42%.
Median patient age was 52 years, with 20% aged 60 or older. A total of 69% were White. About 21% had triple-negative breast cancer; about 21% had hormone receptor–positive, HER2-negative disease; about 25% had hormone receptor–negative, HER2-positive disease; and about 32% had hormone receptor–positive, HER2-positive disease.
Key Results
Outcomes were similar in the 1,556 evaluable patients who did not receive regional nodal irradiation and those who did. The 5-year rates of invasive breast cancer–free recurrence interval were 91.8% and 92.7%, respectively. This primary endpoint was defined as the time from randomization until invasive local, regional, or distant recurrence or breast cancer–related death. Distant recurrence and overall survival rates were also similar in both arms. The 5-year distant recurrence–free rate was 93.4% in each arm of the study. The 5-year overall survival rates were 94% and 93.6%, respectively.
There were few events during the isolated locoregional-free survival interval: 1.4% with no regional nodal irradiation and 0.05% with regional nodal irradiation—for an absolute difference of 0.9% between the treatment arms at 5 years. Disease-free survival rates were almost identical: 88.5% vs 88.3%, respectively. Overall survival results were also similar at 5 years: 94% vs 93.6%, respectively.
Prespecified subgroup analysis showed no difference on the effect of regional nodal irradiation according to type of surgery, hormonal status, and HER2 status.
There were no study-related deaths and no unexpected toxicities. Grade 4 toxicities were rare: 0.1% with no regional nodal irradiation and 0.5% with regional nodal irradiation. The rate of grade 3 toxicities was 6.5% with no regional nodal irradiation and 10% with regional nodal irradiation. The most common grade 3 toxicity was radiation dermatitis (3.3% vs 5.7%, respectively).
“Our findings suggest that downstaging cancer-positive regional lymph nodes with neoadjuvant chemotherapy may allow patients to skip adjuvant regional nodal irradiation without adversely affecting oncologic outcomes. The 10-year from study initiation analysis was important, but long-term follow-up will continue, as we know that additional recurrences can happen later,” said Dr. Mamounas.
Expert Point of View
Kate Lathrop, MD
Kate Lathrop, MD, of UT Health San Antonio, served as moderator of the press conference where the data from NRG Oncology/NSABP B-51/RTOG 1304 were discussed. “These results are eagerly awaited from a difficult trial to conduct that asks an important question: Can we safely omit regional nodal irradiation in patients whose lymph nodes convert from positive to negative following neoadjuvant chemotherapy,” she commented.
“This trial studied an open-ended question. Before this, we did not have data on patients who achieve pathologic complete response. We are using so much more neoadjuvant therapies, and those regimens are getting so much better as we develop targeted therapies. This is very important for patients, so we don’t subject them to additional toxicity, cost, and time to travel for radiation therapy every day. If we know patients can do just as well with or without radiation, this will change opinions about how much radiation to give our patients,” Dr. Lathrop noted.
DISCLOSURE: Dr. Mamounas has served as a consultant to Genentech/Roche, Exact Sciences, Merck, Biotheranostics, and Genzyme-Sanofi; has served on the speakers bureau for Genentech/Roche, Exact Sciences, and Merck; has received honoraria from Genentech/Roche, Exact Sciences, and Merck; and owns stock in Moderna. Dr. Lathrop has received an educational grant from Pfizer.
REFERENCE
1. Mamounas E, Bandos H, White J, et al: Loco-regional irradiation in patients with biopsy-proven axillary node involvement at presentation who become pathologically node-negative after neoadjuvant chemotherapy: Primary outcomes of NRG Oncology/NSABP B-51/RTOG 1304. 2023 San Antonio Breast Cancer Symposium. Abstract GS02-07. Presented December 7, 2023.
