Patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer who present with high-risk clinicopathological features face a heightened likelihood of disease recurrence and may benefit from treatment intensification. Using data from the CANcer TOxicities (CANTO; NCT01993498) cohort, we examined real-world patient characteristics, therapeutic approaches, and survival outcomes in this population. Using data prospectively gathered in the CANTO study between 2012 and 2022, we conducted a retrospective evaluation of patients with high-risk hormone receptor–positive breast cancer. High-risk disease was defined by either extensive nodal involvement (≥4 positive axillary lymph nodes) or limited nodal involvement (1–3 positive axillary lymph nodes) accompanied by unfavorable tumor features, including a tumor diameter of at least 5 cm or histologic grade 3 (cohort 1). A second high-risk classification was also explored, comprising patients with 1–3 positive axillary lymph nodes and elevated proliferative activity, defined by a Ki-67 index of 20% or higher (cohort 2). Time-to-event outcomes were estimated using Kaplan–Meier survival analyses.
Within the CANTO population, patients classified as having high-risk hormone receptor–positive breast cancer accounted for 15.0% and 19.6% of all HR+ cases according to cohorts 1 and 2, respectively. Among the 1,266 individuals included in cohort 1, nearly half (49.0%) presented with involvement of four or more axillary lymph nodes, while 26.0% had primary tumors measuring at least 5 cm and 57.6% were diagnosed with histologic grade III disease. Most patients exhibited a low comorbidity burden, with 79.9% having a favorable Charlson comorbidity index, and 88.1% were diagnosed at stage II or IIIA. Extensive nodal disease (≥10 positive lymph nodes) was observed in 11.8% of cases. Systemic treatment was widely used, with 94.2% of patients receiving (neo)adjuvant chemotherapy. Endocrine therapy was initiated in 97.3% of patients, predominantly aromatase inhibitors; however, treatment was prematurely discontinued in 34.3% of cases, most often due to treatment-related toxicity. Among patients with a minimum follow-up of six years, the estimated 5-year invasive disease–free survival was 79.9% (95% confidence interval [CI], 77.2%–82.4%), and the 5-year distant relapse–free survival reached 83.5% (95% CI, 80.9%–85.7%). This real-world analysis demonstrates that individuals with hormone receptor–positive breast cancer and adverse clinicopathological characteristics experience a substantial risk of early recurrence, even when treated with standard (neo)adjuvant chemotherapy. These findings highlight the urgent need for novel therapeutic strategies for patients at high risk, with particular emphasis on their early integration into the adjuvant treatment setting.
