Ten-year update of HOBOE phase III trial comparing triptorelin plus either tamoxifen or letrozole or zoledronic acid + letrozole in premenopausal hormone receptor-positive early breast cancer patients.

Background: The Hormonal Bone Effects (HOBOE) study tested whether adjuvant triptorelin plus either letrozole (L) or zoledronic acid (Z) plus L (ZL) was more effective than tamoxifen (T) in premenopausal patients with hormone receptor-positive (HR+) early breast cancer (BC). Here we report the long-term follow-up analysis.

Patients and methods: HOBOE (ClinicalTrials.gov number NCT00412022) is an open-label, three-arm, randomised, phase III trial that involved 16 centres in Italy. One thousand and sixty-five premenopausal patients with HR+ early BC receiving triptorelin were randomly assigned (1 : 1 : 1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis.

Results: As of 24 October 2024 at a median follow-up of 9.2 years, 199 DFS events and 79 deaths were reported. Both ZL and L improved DFS over T, with a hazard ratio (HR) of 0.58 [95% confidence interval (CI) 0.41-0.82; P = 0.002] for ZL versus T and 0.69 (95% CI 0.49-0.97, P = 0.030) for L versus T. No statistically significant difference in OS was reported (global log-rank P = 0.103). The previously reported statistically significant interaction with human epidermal growth factor receptor 2 (HER2) status was confirmed for ZL versus T comparison (P = 0.007).

Conclusion: In this updated analysis, L plus triptorelin, with or without Z, demonstrated a statistically significant DFS improvement over T plus triptorelin for the adjuvant treatment of early BC in premenopausal patients.