Adjuvant Therapies May Mitigate Risk of Recurrence in Women With Early-Stage Breast Cancer

Locoregional recurrence (LRR) is reduced by adjuvant therapies, specifically radiation and endocrine therapy (ET), in women with early-stage breast cancer who underwent a lumpectomy, according to a new study published in JAMA Network Open.¹

Breast-conserving therapy (BCT), which consists of a lumpectomy and adjuvant radiotherapy (RT), has been a standard treatment for early-stage breast cancer for decades. However, when these standards were established, disease subtyping and molecular profiling had not been available, thus increasing interest in observation of subgroups with a very low risk of recurrence for de-escalating adjuvant therapy. De-escalating adjuvant therapy is usually achieved by omitting RT even though it may increase the risk of LRR. Current studies seek to further identify the impact of this course of treatment on low-risk groups using molecular and genomic biomarkers, including the Oncotype DX 21-gene recurrence score (ODX RS) that predicts the benefits of chemotherapy and is therefore routinely used in therapy decision-making.² The ODX RS correlates with LRR; a lower score means the tumor is less likely to reoccur after surgery and adjuvant therapy.¹

“Many patients older than 65 years now routinely accept this modestly increased risk of LRR in exchange for omission of RT, although supportive data for younger populations have been lacking,” the study authors wrote.

In this study, researchers aimed to assess the LRR among younger low-risk patients, defined as women aged 50 to 69 years with an ODX RS of 18 or lower who had either estrogen receptor (ER)–positive, progesterone receptor (PR)–positive, or HER2-negative breast cancer with a pathological stage of T1N0 between January 2007 and January 2023. Furthermore, patients who had received 5 or more years of ET or were currently receiving ET at the last follow-up were deemed adherent, whereas those who halted ET within 5 years after initiation were not.

LRR Associations With Adjuvant Therapy and Adherence

The study population consisted of 2249 patients with an ODX RS of 18 or below, who had a median age of 60 years and a median follow-up of 63.3 months. Of them, 2075 (92.3%) received adjuvant RT, whereas 174 (7.7%) did not. Among patients who did not receive RT, 53 were aged 50 to 59 years.

Patients who received RT had a statistically significantly lower risk of LRR (HR, 0.21; 95% CI, 0.08-0.52; P < .001). The incidence of LRR differed significantly by receipt of RT. The estimated 72-month LRR was 8.0% (95% CI, 3.0%-16%) for those not receiving RT compared with 1.1% (95% CI, 0.6%-1.7%) with RT (P < .001). Nevertheless, the 72-month incidence of LRR was lowest among those who received RT regardless of the duration of ET (RT and ≥5 years [or ongoing] ET, 1.1% [95% CI, 0.6%-2.1%] vs RT and <5 years of ET, 0.9% [95% CI, 0.3%-2.1%]).

Comparatively, the highest incidence of LRR was observed in patients who did not receive RT and underwent less than 5 years of ET (72-month LRR, 11.0%; 95% CI, 3.3%-25.0%). However, the incidence of LRR in those who were adherent to ET but did not receive RT was 5.5% (95% CI, 1.0%-16.0%), which was lower than among those receiving neither RT nor ET but higher than in those who did receive RT, regardless of ET adherence.

“These findings demonstrate the effectiveness of adjuvant therapy, particularly RT, even among such low-risk cohorts,” the study authors explained. “These findings also support the potential safety of adjuvant therapy de-escalation through RT or ET omission for patients with breast cancer who are young and with early-stage, low genomic-risk disease, who ordinarily would not be candidates for treatment de-escalation.”

Because this was a retrospective study, the results may have been influenced by bias and patient selection. For example, those who skipped RT were often older, had lower-grade tumors, or were less likely to stick with ET, which could have shaped the outcomes. Because this was a low-risk population, the small number of events limited deeper analysis, meaning prospective studies are still needed to confirm the findings.

“Our results add to a growing body of evidence supporting RT omission among a younger group of carefully selected early-stage breast cancer patients,” the study authors concluded. “Going forward, the ability to safely moderate the complexity of adjuvant therapy may provide meaningful quality-of-life benefits while preserving excellent long-term disease control.”

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. Saad Abdalla Al-Zawi A, Yin SL, Mahmood B, Jalil A, Aladili Z. The Oncotype DX Recurrence Score's impact on the management of estrogen-positive/human epidermal growth factor receptor 2-negative, low-burden axillary status breast cancer (REHAB Study): results of a single center. Cureus. 2022;14(7):e27341. doi:10.7759/cureus.27341