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

Research output: Contribution to journalArticle

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-freesurvival, 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.

Original languageEnglish
Pages (from-to)1179-1188
Number of pages10
JournalJournal of Clinical Oncology
Volume35
Issue number11
DOIs
Publication statusPublished - Apr 10 2017

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Breast
Cholesterol
Breast Neoplasms
letrozole
Tamoxifen
Recurrence
Therapeutics
Hormones
Aromatase Inhibitors
Hypercholesterolemia
Estrogen Receptors
Disease-Free Survival
Arm
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Borgquist, S., Giobbie-Hurder, A., Ahern, T. P., Garber, J. E., Colleoni, M., Láng, I., ... Thürlimann, B. (2017). Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 study. Journal of Clinical Oncology, 35(11), 1179-1188. https://doi.org/10.1200/JCO.2016.70.3116

Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 study. / Borgquist, Signe; Giobbie-Hurder, Anita; Ahern, Thomas P.; Garber, Judy E.; Colleoni, Marco; Láng, István; Debled, Marc; Ejlertsen, Bent; Von Moos, Roger; Smith, Ian; Coates, Alan S.; Goldhirsch, Aron; Rabaglio, Manuela; Price, Karen N.; Gelber, Richard D.; Regan, Meredith M.; Thürlimann, Beat.

In: Journal of Clinical Oncology, Vol. 35, No. 11, 10.04.2017, p. 1179-1188.

Research output: Contribution to journalArticle

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 2017, 'Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 study', Journal of Clinical Oncology, vol. 35, no. 11, pp. 1179-1188. https://doi.org/10.1200/JCO.2016.70.3116
Borgquist, Signe ; Giobbie-Hurder, Anita ; Ahern, Thomas P. ; Garber, Judy E. ; Colleoni, Marco ; Láng, István ; Debled, Marc ; Ejlertsen, Bent ; Von Moos, Roger ; Smith, Ian ; Coates, Alan S. ; Goldhirsch, Aron ; Rabaglio, Manuela ; Price, Karen N. ; Gelber, Richard D. ; Regan, Meredith M. ; Thürlimann, Beat. / Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 study. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 11. pp. 1179-1188.
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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-freesurvival, 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.",
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T1 - Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 study

AU - Borgquist, Signe

AU - Giobbie-Hurder, Anita

AU - Ahern, Thomas P.

AU - Garber, Judy E.

AU - Colleoni, Marco

AU - Láng, István

AU - Debled, Marc

AU - Ejlertsen, Bent

AU - Von Moos, Roger

AU - Smith, Ian

AU - Coates, Alan S.

AU - Goldhirsch, Aron

AU - Rabaglio, Manuela

AU - Price, Karen N.

AU - Gelber, Richard D.

AU - Regan, Meredith M.

AU - Thürlimann, Beat

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N2 - 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-freesurvival, 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.

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