Junichi Kurebayashi1, Eiichi Shiba2, Tatsuya Toyama3, Hiroshi Matsumoto4, Minoru Okazaki5, Tadashi Nomizu6, Tohru Ohtake7, Takaaki Fujii8, Yasuo Ohashi9. 1. Department of Breast and Thyroid Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan. kure@med.kawasaki-m.ac.jp. 2. Department of Breast Surgery, Osaka Breast Clinic, 1-13-8 Ohiraki, Osaka Fukushima-ku, Osaka, 553-0007, Japan. 3. Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya-shi, Aichi, 467-8602, Japan. 4. Division of Breast Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan. 5. Division of Breast Surgery, Sapporo Breast Surgical Clinic, 19-22-6 Kita 6-jonishi, Sapporo Chuo-ku, Hokkaido, 060-0006, Japan. 6. Department of Surgery, Hoshi General Hospital, 159-1 Mukaigawaramachi, Koriyama-shi, Fukushima, 963-8501, Japan. 7. Department of Breast Surgery, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima-City, Fukushima, 960-1295, Japan. 8. Division of Breast and Endocrine Surgery, Gunma University Hospital, 3-39-15 Showamachi, Maebashi-shi, Gunma, 371-8511, Japan. 9. Department of Integrated Science and Technology, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, TokyoTokyo, 112-8551, Japan.
Abstract
BACKGROUND: Previously, we conducted the 5-year open-label, randomized controlled trial (RCT) of leuprorelin adjuvant therapy in post-operative premenopausal patients with endocrine-responsive breast cancer, which was a pilot study to investigate the optimal duration of leuprorelin treatment. Since, however, long-term outcomes became required for the adjuvant endocrine therapy, we performed this follow-up observation study. METHODS: Follow-up observation study was performed up to 10th year after randomization, continuing RCT to evaluate the efficacy and safety of leuprorelin every 3 months for ≥ 3 versus 2 years, with daily tamoxifen for 5 years. Primary endpoints were disease-free survival (DFS) and 2-year landmark DFS. RESULTS:Eligible patients (N = 222) were randomly assigned to receive leuprorelin for either 2 years (N = 112) or ≥ 3 years (N = 110) with tamoxifen. Leuprorelin treatment for ≥ 3 years versus 2 years provided no significant difference in DFS (HR 0.944, 95% CI 0.486-1.8392) or 2-year landmark DFS (N = 99 and 102 in 2-year and ≥ 3-year groups, HR 0.834, 0.397-1.753). In small, higher-risk subgroup (n = 17); however, 2-year landmark DFS in ≥ 3-year group was significantly longer (HR 0.095, 0.011-0.850) than that in 2-year group. The incidence of bone-related adverse events was around 5% in both groups. CONCLUSIONS:Adjuvant leuprorelin treatment for ≥ 3 years with tamoxifen only showed similar efficacy and safety profiles to those for 2 years in analyses among all patients but suggested greater benefit in higher-risk patients. No new safety signal was identified for long-term leuprorelin treatment. TRIAL REGISTRATIONNUMBER: Not applicable. This was an observational study.
RCT Entities:
BACKGROUND: Previously, we conducted the 5-year open-label, randomized controlled trial (RCT) of leuprorelin adjuvant therapy in post-operative premenopausal patients with endocrine-responsive breast cancer, which was a pilot study to investigate the optimal duration of leuprorelin treatment. Since, however, long-term outcomes became required for the adjuvant endocrine therapy, we performed this follow-up observation study. METHODS: Follow-up observation study was performed up to 10th year after randomization, continuing RCT to evaluate the efficacy and safety of leuprorelin every 3 months for ≥ 3 versus 2 years, with daily tamoxifen for 5 years. Primary endpoints were disease-free survival (DFS) and 2-year landmark DFS. RESULTS: Eligible patients (N = 222) were randomly assigned to receive leuprorelin for either 2 years (N = 112) or ≥ 3 years (N = 110) with tamoxifen. Leuprorelin treatment for ≥ 3 years versus 2 years provided no significant difference in DFS (HR 0.944, 95% CI 0.486-1.8392) or 2-year landmark DFS (N = 99 and 102 in 2-year and ≥ 3-year groups, HR 0.834, 0.397-1.753). In small, higher-risk subgroup (n = 17); however, 2-year landmark DFS in ≥ 3-year group was significantly longer (HR 0.095, 0.011-0.850) than that in 2-year group. The incidence of bone-related adverse events was around 5% in both groups. CONCLUSIONS: Adjuvant leuprorelin treatment for ≥ 3 years with tamoxifen only showed similar efficacy and safety profiles to those for 2 years in analyses among all patients but suggested greater benefit in higher-risk patients. No new safety signal was identified for long-term leuprorelin treatment. TRIAL REGISTRATION NUMBER: Not applicable. This was an observational study.
Entities:
Keywords:
Adjuvant endocrine therapy; Endocrine-responsive breast cancer; LH-RH agonist; Ovarian function suppression; Premenopausal patient
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