RNI Omission Yields Low Locoregional Recurrence in HR+, HER2– Breast Cancer

"The incidence of [LRR] observed in this study was reassuringly low, between 1 and 5 years, strongly supporting the need for randomized clinical trials to confirm the safety of omitting RNI in such patients and also providing important evidence for physicians and patients who are unable or unwilling to enroll on a randomized clinical trial of RNI, who require the best available evidence about risks and benefits as this study provides," according to the study authors.

Locoregional recurrence (LRR) rates appeared to be low among patients with hormone receptor (HR)–positive, ERBB2-negative breast cancer who did not receive regional node irradiation (RNI), according to findings from a secondary analysis of the SWOG S1007 trial.

After a median follow-up of 6.1 years, the cumulative incidence of LRR was 0.85% in patients who underwent breast-conserving surgery plus radiotherapy that included RNI, 0.55% in those who received breast-conserving surgery plus radiotherapy but no RNI, 0.11% in those who received mastectomy plus postmastectomy radiotherapy, and 1.7% in those who only received mastectomy. The rate of LRR was 0.48% in a subset of patients who received breast-conserving surgery without RNI, lacked directed supraclavicular targeting, and were treated without targeting of the internal mammary or axillary regions based on a sensitivity analysis.

The incidence of LRR was lower among those who underwent breast-conserving surgery and radiotherapy compared with those who received mastectomy alone (HR, 0.41; 95% CI, 0.19-0.91; P = .03). Investigators identified similar results among postmenopausal patients, although these data were not statistically significant (HR, 0.48; 95% CI, 0.20-1.13; P = .09).

Among premenopausal patients, investigators noted a significant improvement in invasive disease-free survival (IDFS) in those who received breast-conserving surgery vs those who underwent mastectomy alone (P = .03). Moreover, IDFS rates did not differ among those who received breast-conserving surgery plus radiotherapy, those who received mastectomy plus radiotherapy, or those who received mastectomy on its own in the endocrine therapy alone group.

Radiotherapy with or without RNI and surgery type did not impact IDFS outcomes among patients who were premenopausal (P = .17) and postmenopausal (P = .54). When considering receipt of RNI on its own, there were no significant differences in IDFS among patients who were premenopausal (HR, 1.03; 95% CI, 0.74-1.43; P = .87) and postmenopausal (HR, 0.85; 95% CI, 0.68-1.07; P = .16).

“In this secondary analysis of a clinical trial, the current findings suggest a noteworthy split in practice patterns, suggesting true clinical equipoise regarding the need for RNI in patients with breast cancer that involves 1 to 3 lymph nodes and has favorable biology, as indicated by a 21-gene recurrence score of no more than 25,” the study authors wrote. “The incidence of [LRR] observed in this study was reassuringly low, between 1 and 5 years, strongly supporting the need for randomized clinical trials to confirm the safety of omitting RNI in such patients and also providing important evidence for physicians and patients who are unable or unwilling to enroll on a randomized clinical trial of RNI, who require the best available evidence about risks and benefits as this study provides.”

In this secondary analysis of the SWOG S1007 trial, investigators organized a prospective radiotherapy dataset to highlight details of radiotherapy receipt, targets, and dose levels for patients who enrolled on the trial. Those with HR-positive, ERBB2-negative breast cancer and a Oncotype DX 21-gene Breast Recurrence Score of 25 or less were randomly assigned to receive endocrine therapy alone or chemotherapy followed by endocrine therapy.

The primary outcome of the secondary analysis was cumulative LRR in patients grouped by locoregional treatments received. Investigators also assessed the relationship between IDFS and locoregional therapy, stratifying their analyses by menopausal status and adjusting for treatment group, recurrence score, tumor size, number of positive nodes, and receipt of sentinel lymph node biopsy or axillary lymph node dissection.

Investigators reported that 3947 patients in the analysis received radiotherapy. The median patient age was 57 years (range, 18-87). Of 3852 patients who received radiotherapy to the breast or chest wall and had complete information on targets, treatment was administered to the breast or chest wall alone in 32.8%. Additionally, 59.0% of this group received RNI with at least a supraclavicular field, 13.9% underwent treatment to the internal mammary region, and 32.4% received treatment to the axilla.

Among patients who received breast conserving surgery plus radiotherapy with RNI, those who received breast-conserving surgery plus radiotherapy with no RNI, those who received mastectomy plus radiotherapy, and those who received mastectomy alone, respectively, most were 50 to 59 years old (34.1% vs 33.9% vs 31.6% vs 33.2%). In each respective group, most patients were postmenopausal (69.6% vs 70.0% vs 58.1% vs 65.6%), had 1 positive node (60.5% vs 76.3% vs 53.4% vs 69.2%), and had a recurrence score of 14 to 25 (57.5% vs 57.1% vs 55.6% vs 58.2%).

The study investigators noted that the limited follow-up and the fact that patients with estrogen receptor–positive disease may have recurrence later were potential limitations to their findings.

Reference

Jagsi R, Barlow WE, Woodward WA, et al. Radiotherapy use and incidence of locoregional recurrence in patients with favorable-risk, node-positive breast cancer enrolled in the SWOG S1007 trial. JAMA Oncol. Published online July 6, 2023. doi:10.1001/jamaoncol.2023.1984