Abstract
BackgroundPreviously, 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.MethodsFollow-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.ResultsEligible 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.ConclusionsAdjuvant 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 numberNot applicable. This was an observational study.
Highlights
Adjuvant treatment with tamoxifen has been established as a standard therapy for pre- and postmenopausal women with estrogen-receptor (ER)-positive early breast cancer [1,2,3,4]; it can stimulate pituitary-ovarian function, accompanied by increased serum estradiol (E2) levels [5]
The randomized controlled trial (RCT) with a 5-year study period was conducted at 19 sites in Japan, and 222 patients were enrolled between July 2006 and July 2008, randomly assigned to two groups, and received leuprorelin for either 2 years (N = 112) or ≥ 3 years (N = 110), respectively (Figs. 1 and 2)
We evaluated the association of these clinical factors with disease-free survival (DFS) risk retrospectively by the subgroup analysis in 2-year group (n = 112) using univariate Cox model
Summary
Adjuvant treatment with tamoxifen has been established as a standard therapy for pre- and postmenopausal women with estrogen-receptor (ER)-positive early breast cancer [1,2,3,4]; it can stimulate pituitary-ovarian function, accompanied by increased serum estradiol (E2) levels [5]. Based on the randomized clinical trials, which showed a significant survival benefit of the combination of tamoxifen plus LH-RH agonist [10,11,12], the combination has been used as a postoperative adjuvant therapy for premenopausal women with endocrine-responsive early breast cancer [13]. 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. 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.
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