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

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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 : official journal of the American Society of Clinical Oncology, bind 35, nr. 11, s. 1179-1188. https://doi.org/10.1200/JCO.2016.70.3116

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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 : official journal of the American Society of Clinical Oncology. 35(11):1179-1188. https://doi.org/10.1200/JCO.2016.70.3116

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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. I: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017 ; Bind 35, Nr. 11. s. 1179-1188.

Bibtex

@article{5a26c1fad93c40af85d48b527f546e76,
title = "Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study",
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.",
keywords = "Aged, Anticholesteremic Agents, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Chemotherapy, Adjuvant, Cholesterol, Disease-Free Survival, Double-Blind Method, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Mastectomy, Segmental, Middle Aged, Neoplasm Recurrence, Local, Nitriles, Proportional Hazards Models, Radiotherapy, Adjuvant, Receptors, Estrogen, Receptors, Progesterone, Tamoxifen, Triazoles, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial",
author = "Signe Borgquist and Anita Giobbie-Hurder and Ahern, {Thomas P} and Garber, {Judy E} and Marco Colleoni and Istv{\'a}n L{\'a}ng and Marc Debled and Bent Ejlertsen and {von Moos}, Roger and Ian Smith and Coates, {Alan S} and Aron Goldhirsch and Manuela Rabaglio and Price, {Karen N} and Gelber, {Richard D} and Regan, {Meredith M} and Beat Th{\"u}rlimann",
year = "2017",
month = "4",
day = "10",
doi = "10.1200/JCO.2016.70.3116",
language = "English",
volume = "35",
pages = "1179--1188",
journal = "Molecular and Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "11",

}

RIS

TY - JOUR

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

PY - 2017/4/10

Y1 - 2017/4/10

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-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.

AB - 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.

KW - Aged

KW - Anticholesteremic Agents

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Breast Neoplasms

KW - Chemotherapy, Adjuvant

KW - Cholesterol

KW - Disease-Free Survival

KW - Double-Blind Method

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Hypercholesterolemia

KW - Mastectomy, Segmental

KW - Middle Aged

KW - Neoplasm Recurrence, Local

KW - Nitriles

KW - Proportional Hazards Models

KW - Radiotherapy, Adjuvant

KW - Receptors, Estrogen

KW - Receptors, Progesterone

KW - Tamoxifen

KW - Triazoles

KW - Clinical Trial, Phase III

KW - Journal Article

KW - Randomized Controlled Trial

U2 - 10.1200/JCO.2016.70.3116

DO - 10.1200/JCO.2016.70.3116

M3 - Journal article

VL - 35

SP - 1179

EP - 1188

JO - Molecular and Clinical Oncology

JF - Molecular and Clinical Oncology

SN - 0732-183X

IS - 11

ER -

ID: 52152400