Patients diagnosed with hormone receptor-positive, HER2-negative breast cancer (HR+ BC) exhibiting poor prognostic factors face a heightened likelihood of disease recurrence and are suitable candidates for escalated therapeutic options. We examined real-world clinicopathological profiles, management strategies, and oncologic outcomes in this population using data from the CANcer TOxicities (CANTO) cohort (NCT01993498).This retrospective review utilized prospectively acquired data from CANTO, spanning 2012 to 2022. High-risk HR+ BC was identified by either ≥4 involved axillary lymph nodes (LNs) or 1–3 involved LNs plus tumor diameter ≥5 cm or grade 3 histology (cohort 1). A separate criterion included 1–3 involved LNs with Ki-67 ≥20% (cohort 2). Survival curves were generated via the Kaplan–Meier approach. Within the CANTO dataset, high-risk HR+ BC cases comprised 15.0%–19.6% of all HR+ BC patients (cohorts 1 and 2, respectively). In cohort 1 (n=1266), 617 individuals (49.0%) showed ≥4 LNs, 327 (26.0%) had tumors ≥5 cm, and 727 (57.6%) displayed grade III histology. A favorable Charlson comorbidity index was observed in 79.9%, with 88.1% presenting stage II/IIIA disease. Involvement of ≥10 LNs occurred in 11.8%. (Neo)adjuvant chemotherapy was given to 94.2% of patients. Endocrine treatment was started in 97.3%, primarily aromatase inhibitors, but stopped in 34.3% due mostly to side effects. For those enrolled ≥6 years before data cutoff, 5-year invasive disease-free survival reached 79.9% [95% confidence interval (CI) 77.2% to 82.4%], while 5-year distant relapse-free survival was 83.5% (95% CI 80.9% to 85.7%). These real-world findings affirm that HR+ BC patients with adverse prognostic indicators continue to experience substantial early recurrence risk during adjuvant therapy, even after (neo)adjuvant chemotherapy. Urgent development and early integration of new treatment modalities into the adjuvant regimen are needed for this high-risk group.
