title: A randomized controlled study evaluating safety and efficacy of leuprorelin acetate every-3-months depot for 2 versus 3 or more years with tamoxifen for 5 years as adjuvant treatment in premenopausal patients with endocrine-responsive breast cancer.
abstract: BACKGROUND
  Luteinizing hormone-releasing hormone (LH-RH) agonists provide effective adjuvant treatment for premenopausal women with endocrine-responsive breast cancer. Here, we investigated appropriate treatment durations of an LH-RH agonist, leuprorelin.
  
  
  METHODS
  We conducted an open-label, randomized controlled pilot study to evaluate the safety and efficacy of leuprorelin subcutaneously administered every-3-months for 2 versus 3 or more, up to 5 years, together with daily tamoxifen for 5 years in premenopausal endocrine-responsive breast cancer patients. Primary endpoints were disease-free survival (DFS) and safety.
  
  
  RESULTS
  Eligible patients (N = 222) were randomly assigned to receive leuprorelin for either 2 years (N = 112) or 3 or more years (N = 110) with tamoxifen for 5 years after surgery. Leuprorelin treatment for 3 or more years provided no significant difference in DFS rate over 2 years: 94.1 versus 91.8 % at 144 weeks (3 years) after the second year (week 96) and 90.8 versus 90.4 % at the fifth year (week 240). The overall survival rate was 100 % for both groups during the third through fifth year study period. There were no significant differences in the incidence of adverse events (AEs) between the 2 groups: most AEs were rated grade 1 or 2.
  
  
  CONCLUSIONS
  Adjuvant leuprorelin treatment for 3 or more years with tamoxifen showed a survival benefit and safety profile similar to that for 2 years in premenopausal endocrine-responsive breast cancer patients. No new safety signal was identified for long-term leuprorelin treatment. Longer follow-up observation is needed to determine the optimal duration of leuprorelin treatment.
authors: Department of Breast Surgery, Osaka Breast Clinic, 1-3-4 Fukushima, Fukushima-ku, Osaka, 553-0003, Japan. eshiba@goo.jp.
authors: Eiichi
authors: E
authors: Shiba
authors: Department of Breast and Endocrine Surgery, Nagoya City University Hospital, Nagoya, Japan.|Department of Breast Surgery, Hokkaido University Hospital, Sapporo, Japan.
authors: Hiroko
authors: H
authors: Yamashita
authors: Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, Japan.
authors: Junichi
authors: J
authors: Kurebayashi
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Shinzaburo
authors: S
authors: Noguchi
authors: Department of Breast and Endocrine Surgery, Kumamoto University, Kumamoto, Japan.
authors: Hirotaka
authors: H
authors: Iwase
authors: Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan.
authors: Yasuo
authors: Y
authors: Ohashi
authors: Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors: Kiyofumi
authors: K
authors: Sasai
authors: Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors: Tsukasa
authors: T
authors: Fujimoto
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D017697:Premenopause; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D004958:Estradiol; D016729:Leuprolide
keywords: Adjuvant endocrine therapy; Disease-free survival (DFS); Leuprorelin acetate; Premenopausal endocrine-responsive breast cancer; Safety
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