Analysis of Radiotherapy and Breast Cancer Recurrence in the RxPONDER Trial

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Do patients with breast cancer and a low 21-gene recurrence score need regional node irradiation to reduce their risk of locoregional recurrence? An analysis of RxPONDER trial data suggests only a randomized clinical trial devoted to this question can provide a decisive answer.

An analysis of data on the use of radiation therapy in a large clinical trial of patients with hormone receptor–positive, HER2-negative breast cancer who had one to three involved lymph nodes and a 21-gene recurrence score of 25 or less found that rates of locoregional recurrence of the disease were low regardless of whether a patient had received regional node irradiation. The results suggest that a randomized clinical trial is required to answer the question of whether these favorable-risk patients can safely skip regional node irradiation.

The analysis was performed using patient data from the S1007 RxPONDER trial conducted by the SWOG Cancer Research Network. The work was presented in an oral scientific session at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting by Reshma Jagsi, MD, DPhil, and colleagues (Abstract 172).

Reshma Jagsi, MD, DPhil

Reshma Jagsi, MD, DPhil

“We’ve known for a very long time that treating regional lymph nodes with radiation in patients with node-positive breast cancer can improve locoregional recurrence rates and overall survival,” said Dr. Jagsi, a SWOG investigator and Newman Family Professor of Radiation Oncology at the University of Michigan. “But we haven’t known whether all patients with node-positive breast cancer need this, or whether—especially with modern therapies and our ability to use prognostic scores—certain patients may safely forego regional node irradiation.”

Regional Node Irradiation

Regional node irradiation for breast cancer is radiation therapy applied to the lymph nodes that drain the region around a tumor—for example, near the collarbone or breastbone. It is often given after mastectomy or breast-conserving surgery for breast cancer. But there are not extensive data on how frequently regional node irradiation is used or in what circumstances when patients have favorable-risk breast cancer with one to three involved lymph nodes. Data are also scarce on how the use of regional node irradiation in these patients is associated with a patient’s risk of locoregional recurrence.

RxPONDER Analysis

To answer these questions, Dr. Jagsi’s team looked at data from almost 5,000 patients who took part in the S1007 RxPONDER trial. This study randomly assigned patients with hormone receptor–positive, HER2-negative breast cancer with an OncotypeDX 21-gene recurrence score of 25 or lower to either chemotherapy followed by endocrine therapy or endocrine therapy alone. The primary clinical results of the study were reported by Kalinsky et al in The New England Journal of Medicine in December 2021.

The authors of the analysis presented at the ASTRO Annual Meeting evaluated how often regional node irradiation was used in these patients and analyzed the associated patterns of locoregional recurrence and invasive disease­–free survival from 1 to 5 years after a patient’s randomization to the trial. They found that practice was almost evenly divided on the use of regional node irradiation, and that rates of locoregional recurrence were quite low—even in patients who had not received regional node irradiation.

The larger question the researchers hoped to find clues to is whether patients with recurrence scores of 25 or less—indicating they are at lower risk of their cancer recurring—may be at such a low level of risk for locoregional recurrence that it would be reasonable to consider foregoing regional node irradiation.

Next Steps

Dr. Jagsi said their findings reveal that “patients and radiation oncologists are voting with their feet to say there’s not really a clear answer” to this larger question of whether favorable-risk patients can skip regional node irradiation. Instead, she said, their findings make clear that results from a randomized clinical trial focused on this specific question will be needed to answer it definitively.

Such a trial is currently underway—the TAILOR RT trial (NCIC MA-39) being led by the Canadian Cancer Trials Group, with co-sponsorship of the National Cancer Institute. 

“It’s encouraging to see these results,” Dr. Jagsi said. “They suggest the TAILOR RT trial is very important. Hopefully, our results will encourage physicians and patients alike to enroll to the trial to get an answer.”

Disclosure: The RxPONDER S1007 study is supported by the NCI, part of the National Institutes of Health (NIH), led by SWOG, and conducted by the NIH-funded National Clinical Trials Network (NCTN). S1007 was funded by NIH/NCI grants CA180888 and CA180819 and was supported in part by Genomic Health (Exact Sciences Corporation). Dr. Jagsi's research was supported by a Senior Scholar grant from the Susan G. Komen Foundation. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.