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

View/ Open
Publication Date
2017-04-10Author
Borgquist, S
Giobbie-Hurder, A
Ahern, TP
Garber, JE
Colleoni, M
Láng, I
Debled, M
Ejlertsen, B
von Moos, R
Smith, I
Coates, AS
Goldhirsch, A
Rabaglio, M
Price, KN
Gelber, RD
Regan, MM
Thürlimann, B
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Version of record
Subject
Aged
Anticholesteremic Agents
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Chemotherapy, Adjuvant
Cholesterol
Disease-Free Survival
Double-Blind Method
Female
Follow-Up Studies
Humans
Hypercholesterolemia
Letrozole
Mastectomy, Segmental
Middle Aged
Neoplasm Recurrence, Local
Nitriles
Proportional Hazards Models
Radiotherapy, Adjuvant
Receptors, Estrogen
Receptors, Progesterone
Tamoxifen
Triazoles
Research team
Medicine (RMH Smith Cunningham)
Language
eng
License start date
2017-04-10
Citation
J Clin Oncol, 2017, 35 (11), pp. 1179 - 1188