Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study

Signe Borgquist, Anita Giobbie-Hurder, Thomas P Ahern, Judy E Garber, Marco Colleoni, István Láng, Marc Debled, Bent Ejlertsen, Roger von Moos, Ian Smith, Alan S Coates, Aron Goldhirsch, Manuela Rabaglio, Karen N Price, Richard D Gelber, Meredith M Regan, Beat Thürlimann

    91 Citationer (Scopus)

    Abstract

    Purpose 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. Patients and Methods 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-positive 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-free interval, and distant recurrence-free interval. Results 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-free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence-free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor-positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials.

    OriginalsprogEngelsk
    TidsskriftJournal of clinical oncology : official journal of the American Society of Clinical Oncology
    Vol/bind35
    Udgave nummer11
    Sider (fra-til)1179-1188
    Antal sider10
    ISSN0732-183X
    DOI
    StatusUdgivet - 10 apr. 2017

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