{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:25:45Z","timestamp":1792218345683,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,10,10]],"date-time":"2011-10-10T00:00:00Z","timestamp":1318204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>Postmenopausal breast cancer (BC) patients receiving adjuvant aromatase inhibitor therapy are at risk of progressive bone loss and fractures. Zoledronic acid inhibits osteoclastic bone resorption, is effective in maintaining bone health, and may therefore be beneficial in this setting.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>Overall, 602 postmenopausal women with early, hormone receptor\u2010positive BC receiving adjuvant letrozole were randomized (301 each group) to receive upfront or delayed\u2010start zoledronic acid (4 mg intravenously every 6 months) for 5 years. The primary endpoint was the change in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary endpoints included changes in LS BMD, total hip BMD, and bone turnover markers at 2, 3, and 5 years; fracture incidence at 3 years; and time to disease recurrence.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>At month 61, the adjusted mean difference in LS and total hip BMDs between the upfront and delayed groups was 8.9% and 6.7%, respectively (<jats:italic>P<\/jats:italic> &lt; .0001, for both). Approximately 25% of delayed patients received zoledronic acid by month 61. Only 1 patient experienced grade 4 renal dysfunction; no confirmed cases of osteonecrosis of the jaw were reported. Fracture rates (upfront, 28 [9.3%]; delayed, 33 [11%]; <jats:italic>P<\/jats:italic> = .3803) and Kaplan\u2010Meier disease recurrence rates (upfront, 9.8 [95% confidence interval (CI), 6.0\u201010.3]; delayed, 10.5 [95% CI, 6.6\u201014.4]; <jats:italic>P<\/jats:italic> = .6283) were similar at month 61.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>Upfront zoledronic acid seems to be the preferred treatment strategy versus delayed administration, as it significantly and progressively increases BMD in postmenopausal women with early BC receiving letrozole for 5 years, and long\u2010term coadministration of letrozole and zoledronic acid is well tolerated. Cancer 2012. \u00a9 2011 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.26313","type":"journal-article","created":{"date-parts":[[2011,10,10]],"date-time":"2011-10-10T15:16:33Z","timestamp":1318259793000},"page":"1192-1201","source":"Crossref","is-referenced-by-count":166,"title":["Final 5\u2010year results of Z\u2010FAST trial"],"prefix":"10.1002","volume":"118","author":[{"given":"Adam M.","family":"Brufsky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Graydon","family":"Harker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Thaddeus","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Bosserman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Seidler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixian","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghulam","family":"Warsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza","family":"Argonza\u2010Aviles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hohneker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solveig G.","family":"Ericson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith A.","family":"Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,10,10]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.0726"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.3744"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2007-0206"},{"key":"e_1_2_7_5_2","unstructured":"National Comprehensive Cancer Network. 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