Adjuvant Endocrine/Radiation Therapy May Limit Breast Cancer Recurrence

Administering endocrine therapy or radiation to patients with early-stage breast cancer in the adjuvant setting may reduce locoregional recurrence (LRR) rates, according to findings from a cohort study published in JAMA Network Open.¹

Based on univariate analysis, receipt of adjuvant radiotherapy correlated with significantly lower odds of LRR (HR, 0.21; 95% CI, 0.08-0.52; P <.001), while a higher Oncotype DX 21-gene recurrence score (ODX RS) conferred an elevated risk (HR, 1.16; 95% CI, 1.05-1.28; P = .005). Additionally, multivariate analysis showed that adjuvant radiotherapy still showed a significant association with LRR (HR, 0.21; 95% CI, 0.09-0.52; P <.001); ODX RS also independently correlated with LRR risk (HR, 1.16; 95% CI, 1.05-1.28; P = .005).

At 72 months, the estimated cumulative LRR rate was 8.0% (95% CI, 3.0%-16%) in patients who did not receive radiotherapy vs 1.1% (95% CI, 0.6%-1.7%) in those who did (P <.001). The highest estimates of LRR at 72 months occurred among patients with no radiotherapy and receipt of endocrine therapy for fewer than 5 years (11.0%; 95% CI, 3.3%-25.0%).

Univariate Cox regression analysis indicated that adjuvant radiotherapy significantly correlated with prolonged disease-free survival (DFS; HR, 0.38; 95% CI, 0.19-0.77; P = .007). DFS also appeared to be significantly longer in patients with 5 or more years of ongoing endocrine therapy vs those with fewer than 5 years (HR, 0.53; 95% CI, 0.34-0.82; P = .004). ODX RS showed no significant relationship with DFS outcomes, and receipt of radiotherapy did not correlate with overall survival (OS).

“In this cohort study of patients aged 50 to 69 years who underwent lumpectomy for early-stage breast cancer with ODX RS of 18 or lower, we found very low estimated LRR rates among patients who received adjuvant therapy,” lead study author David Gibbes Miller, MD, MSc, from the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, wrote with coauthors in the publication.¹ “The LRR rates remained low among patients who omitted adjuvant [radiotherapy] or were [endocrine therapy] nonadherent.”

Investigators of this study assessed a cohort of younger low-risk patients with low ODX RS and hormone receptor–positive, HER2-negative breast cancer who received various regimens of adjuvant endocrine therapy and radiotherapy. The analysis included 2249 patients who underwent lumpectomy and endocrine therapy with or without adjuvant radiation from January 2007 to January 2023.

The primary end point of the study was LRR, defined as the time from surgery to breast cancer recurrence, with distant recurrence contralateral breast cancer, and death as competing risks. Secondary end points included DFS, time to distant metastasis, and OS.

Patients 50 to 69 years old with a pathologic stage of T1N0, an ODX RS of 18 or lower, and negative surgical margins were eligible for inclusion in the study. Those with prior chemotherapy and bilateral breast cancer were not included.

The median patient age was 60 years (IQR, 55-65), and the median follow-up was 63.3 months (IQR, 34.1-96.0). Overall, 2075 patients received adjuvant radiotherapy, and 174 did not. The most common treatment among patients who received radiotherapy was whole breast radiation (60.9%; n = 1263), and the majority underwent sentinel lymph node biopsy (98.8%; n = 2221).

With the context of ongoing studies assessing the implications of radiotherapy omission in younger populations, the study authors noted that their analysis serves as a “pragmatic” evaluation of outcomes for younger patients with early-stage, low genomic-risk breast cancer. Additionally, the authors highlighted various limitations of their analysis. For example, the low-risk nature of the patient population may have correlated with a low event rate, thereby complicating the ability to conduct other extensive multivariate analyses.

References

1. Miller DG, Boe LA, Wen HY, et al. Adjuvant radiation and endocrine therapy in early-stage breast cancer with low genomic risk. JAMA Netw Open. 2025;8;(9):e2532305. doi:10.1001/jamanetworkopen.2025.32305
2. White JR, Anderson SJ, Harris EE, et al.NRG-BR007: A phase III trial evaluating de-escalation of breast radiation (DEBRA) following breast-conserving surgery (BCS) of stage 1, hormone receptor+, HER2-, RS ≤18 breast cancer. J Clin Oncol. 2022;40(16)(suppl):TPS613-TPS613. doi:10.1200/JCO.2022.40.16_suppl.TPS613