There's a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.
Do patients still need regional nodal irradiation or can they skip it?
Currently, it's about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.
Until now, Mamounas's own institution has opted for regional irradiation just to be on the safe side, but he said that's going to change in the wake of a multicenter trial he presented at the 2023 San Antonio Breast Cancer Symposium.
Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest.
Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.
In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone.
All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients.
Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.
Patients in both groups also demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.
The team also did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs 0.5% in the irradiation group.
The trial answers "a very important question," according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation.
The trial results were "highly awaited" because "we didn't have the data to make these" decisions, Lathrop said.
Knowing these patients do just as well without regional nodal irradiation is "going to change a lot of opinions," said Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.
Because recurrences can still occur after 5 years, Mamounas's team will continue to follow the women, but he believes "it's very unlikely that long-term distant disease-free survival will change."
Based on the study, "we will omit" regional nodal irradiation for women who fit the study criteria, Mamounas said.
When asked if women should ask their doctors about skipping regional nodal irradiation, Mamounas said "absolutely."
"I think it requires a discussion at this point," he explained. "Based on the data, it's a reasonable conclusion that radiotherapy can be avoided" in many cases, such as in lower-stage women with one initially positive node.
Mamounas also thinks patients will be interested in the approach "because they are really looking to avoid radiotherapy" if they can.
The work was funded by the National Cancer Institute. Mamounas has been a consultant and speaker for Genentech, Merck, and an advisor for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
M. Alexander Otto is a physician assistant with a master's degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com
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