{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:08:30Z","timestamp":1790874510426,"version":"4.1.0"},"reference-count":37,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"11","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2017,4,10]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor\u2013positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-free-survival, breast cancer\u2013free interval, and distant recurrence\u2013free interval. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer\u2013free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence\u2013free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor\u2013positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2016.70.3116","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T17:11:27Z","timestamp":1487869887000},"page":"1179-1188","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":116,"title":["Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study"],"prefix":"10.1200","volume":"35","author":[{"given":"Signe","family":"Borgquist","sequence":"first","affiliation":[{"name":"Signe Borgquist and Judy E. Garber, Dana-Farber Cancer Institute, Harvard Medical School; Anita Giobbie-Hurder, International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute; Richard D. Gelber, IBCSG Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, T.H. Chan Harvard School of Public Health, and Frontier Science and Technology Research Foundation; Karen N. Price, IBCSG Statistical Center and Frontier Science and Technology Research Foundation;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Giobbie-Hurder","sequence":"additional","affiliation":[{"name":"Signe Borgquist and Judy E. Garber, Dana-Farber Cancer Institute, Harvard Medical School; Anita Giobbie-Hurder, International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute; Richard D. Gelber, IBCSG Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, T.H. Chan Harvard School of Public Health, and Frontier Science and Technology Research Foundation; Karen N. Price, IBCSG Statistical Center and Frontier Science and Technology Research Foundation;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Ahern","sequence":"additional","affiliation":[{"name":"Signe Borgquist and Judy E. Garber, Dana-Farber Cancer Institute, Harvard Medical School; Anita Giobbie-Hurder, International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute; Richard D. Gelber, IBCSG Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, T.H. Chan Harvard School of Public Health, and Frontier Science and Technology Research Foundation; Karen N. Price, IBCSG Statistical Center and Frontier Science and Technology Research Foundation;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy E.","family":"Garber","sequence":"additional","affiliation":[{"name":"Signe Borgquist and Judy E. Garber, Dana-Farber Cancer Institute, Harvard Medical School; Anita Giobbie-Hurder, International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute; Richard D. Gelber, IBCSG Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, T.H. Chan Harvard School of Public Health, and Frontier Science and Technology Research Foundation; Karen N. Price, IBCSG Statistical Center and Frontier Science and Technology Research Foundation;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Colleoni","sequence":"additional","affiliation":[{"name":"Signe Borgquist and Judy E. Garber, Dana-Farber Cancer Institute, Harvard Medical School; Anita Giobbie-Hurder, International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute; Richard D. Gelber, IBCSG Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, T.H. 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