{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:44:24Z","timestamp":1787496264119,"version":"build-2736575974"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation"},{"name":"Takeda Pharmaceutical Company Limited"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Follow-up observation study was performed up to 10th year after randomization, continuing RCT to evaluate the efficacy and safety of leuprorelin every 3\u00a0months for\u2009\u2265\u20093 versus 2\u00a0years, with daily tamoxifen for 5\u00a0years. Primary endpoints were disease-free survival (DFS) and 2-year landmark DFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eligible patients (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009222) were randomly assigned to receive leuprorelin for either 2\u00a0years (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009112) or\u2009\u2265\u20093\u00a0years (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009110) with tamoxifen. Leuprorelin treatment for\u2009\u2265\u20093\u00a0years versus 2\u00a0years provided no significant difference in DFS (HR 0.944, 95% CI 0.486\u20131.8392) or 2-year landmark DFS (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200999 and 102 in 2-year and\u2009\u2265\u20093-year groups, HR 0.834, 0.397\u20131.753). In small, higher-risk subgroup (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200917); however, 2-year landmark DFS in\u2009\u2265\u20093-year group was significantly longer (HR 0.095, 0.011\u20130.850) than that in 2-year group. The incidence of bone-related adverse events was around 5% in both groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Adjuvant leuprorelin treatment for\u2009\u2265\u20093\u00a0years with tamoxifen only showed similar efficacy and safety profiles to those for 2\u00a0years in analyses among all patients but suggested greater benefit in higher-risk patients. No new safety signal was identified for long-term leuprorelin treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>Not applicable. This was an observational study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12282-020-01205-w","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T02:02:36Z","timestamp":1614391356000},"page":"684-697","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A follow-up study of a randomized controlled study evaluating safety and efficacy of leuprorelin acetate every-3-month depot for 2 versus 3 or more years with tamoxifen for 5\u00a0years as adjuvant treatment in premenopausal patients with endocrine-responsive breast cancer"],"prefix":"10.1007","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0356-842X","authenticated-orcid":false,"given":"Junichi","family":"Kurebayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Shiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Toyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Okazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Nomizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Ohtake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"1205_CR1","doi-asserted-by":"crossref","unstructured":"Early Breast Cancer Trialists' Collaborative Group (EBCTCG). 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Dr. Toyama received personal fees from AstraZeneca K.K., outside the submitted work. Dr. Toyama also received grants and personal fees from Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K., Novartis Pharma K.K., Pfizer Japan Inc., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Nippon Kayaku Co., Ltd., and Kyowa Kirin Co., Ltd., outside the submitted work. Prof. Ohashi received grants from Medical Member System, outside the submitted work. Prof. Ohashi also received personal fees from Statcom Company Limited, Daiichi Sankyo Company, Limited, Chugai Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Taiho Pharmaceutical Co., Ltd., Sanofi K.K., and EP-CRSU Co., Ltd., outside the submitted work. The other authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}