Outcome without any adjuvant systemic treatment in stage I ER+/HER2- breast cancer patients included in the MINDACT trial.

ABSTRACT Background Adjuvant systemic treatments (AST) reduce mortality, but have associated short- and long-term toxicities. Careful selection of patients likely to benefit from AST is needed. We evaluated outcome of low-risk breast cancer patients of the EORTC 10041/BIG 3-04 MINDACT trial who received no AST. Patients and methods Patients with estrogen receptor positive, HER2 negative, lymph node negative tumors ≤2cm who received no AST were matched 1:1 to patients with similar tumor characteristics treated with adjuvant endocrine therapy (ET), using propensity score matching and exact matching on age, genomic risk (70-gene signature) and grade. In a posthoc analysis, distant metastasis-free interval (DMFI) and overall survival (OS) were assessed by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. Cumulative incidences of locoregional recurrence (LRR) and contralateral breast cancer (CBC) were assessed with competing risk analyses. Results At 8 years, DMFI rates were 94.8% (95%CI: 92.7-96.9%) in 509 patients receiving no AST, and 97.3% (95%CI: 95.8-98.8%) in 509 matched patients who received only ET (absolute difference: 2.5%, HR 0.56 (95%CI: 0.30-1.03)). No statistically significant difference was seen in 8-year OS rates, 95.4% (95%CI: 93.5-97.4%) in patients receiving no AST, and 95.6% (95%CI: 93.8-97.5%) in patients receiving only ET (absolute difference: 0.2%, HR 0.86 (95%CI: 0.53-1.41)). Cumulative incidence rates of LRR and CBC were 4.7% (95%CI: 3.0-7.0%) and 4.6% (95%CI: 2.9-6.9%) in patients receiving no AST versus 1.4% (95%CI: 0.6-2.9%) and 1.5% (95%CI: 0.6-3.1%) in patients receiving only ET. Conclusions In patients with stage I low-risk breast cancer, the effect of ET on DMFI was limited, but overall significantly fewer breast cancer events were observed in patients who received ET, after the relatively short follow-up of 8 years. These benefits and side effects of ET should be discussed with all patients, even those at a very low risk of distant metastasis.