Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer: HOBOE phase 3 randomised trial

Francesco Perrone, Michelino De Laurentiis, Sabino De Placido, Michele Orditura, Saverio Cinieri, Ferdinando Riccardi, Angela Stefania Ribecco, C. Putzu, L. Del Mastro, Emanuela Rossi, Vincenza Tinessa, Anna Maria Mosconi, Francesco Nuzzo, Francesca Di Rella, Adriano Gravina, Giovanni Iodice, Gabriella Landi, Carmen Pacilio, Valeria Forestieri, Rossella LauriaAgnese Fabbri, Toni Ibrahim, Ermelinda De Maio, Sandro Barni, Stefania Gori, Vittorio Simeon, L. Arenare, Gennaro Daniele, Maria Carmela Piccirillo, Nicola Normanno, Andrea de Matteis, Ciro Gallo

Research output: Contribution to journalArticlepeer-review


Aim: The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor–positive (HR+) tumours. Patients and methods: In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and 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: With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4%, 93.2% and 93.3% with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95% confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95% CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95% CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3%, 7.3% and 16.6% patients, and in the safety population, grade 3–4 side-effects were reported in 4.2%, 6.9% and 9.1% patients treated with T, L or ZL, respectively. Conclusion: HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. (NCT00412022)

Original languageEnglish
Pages (from-to)178-186
Number of pages9
JournalEuropean Journal of Cancer
Publication statusPublished - Sep 1 2019


  • Adjuvant endocrine treatment
  • Aromatase inhibitors
  • Breast cancer
  • Phase 3
  • Premenopausal patients
  • Zoledronic acid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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