Cardiovascular adverse events during adjuvant endocrine therapy for early breast cancer using letrozole or tamoxifen: safety analysis of BIG 1-98 trial.
OBJECTIVE
Previous analyses of adjuvant studies of aromatase inhibitors versus tamoxifen, including the Breast International Group (BIG) 1-98 study, have suggested a small numerical excess of cardiac adverse events (AEs) on aromatase inhibitors, a reduction in the incidence of hypercholesterolemia on tamoxifen, and significantly higher incidence of thromboembolic AEs on tamoxifen. The purpose of the present study is to provide detailed updated information on these AEs in BIG 1-98.


METHODS
Eight thousand twenty-eight postmenopausal women with receptor-positive early breast cancer were randomly assigned (double-blind) between March 1998 and May 2003 to receive 5 years of adjuvant endocrine therapy with letrozole, tamoxifen, or a sequence of these agents. Seven thousand nine hundred sixty-three patients who actually received therapy are included in this safety analysis, which focuses on cardiovascular events. AE recording ceased 30 days after therapy completion (or after switch on the sequential arms).


RESULTS
Baseline comorbidities were balanced. At a median follow-up time of 30.1 months, we observed similar overall incidence of cardiac AEs (letrozole, 4.8%; tamoxifen, 4.7%), more grade 3 to 5 cardiac AEs on letrozole (letrozole, 2.4%; tamoxifen, 1.4%; P = .001)--an excess only partially attributable to prior hypercholesterolemia--and more overall (tamoxifen, 3.9%; letrozole, 1.7%; P < .001) and grade 3 to 5 thromboembolic AEs on tamoxifen (tamoxifen, 2.3%; letrozole, 0.9%; P < .001). There was no significant difference between tamoxifen and letrozole in incidence of hypertension or cerebrovascular events.


CONCLUSIONS
The present safety analysis, limited to cardiovascular AEs in BIG 1-98, documents a low overall incidence of cardiovascular AEs, which differed between treatment arms.
Mouridsen
Henning
H
Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen, Denmark. henning.mouridsen@rh.hosp.dk
Keshaviah
Aparna
A
Coates
Alan S
AS
Rabaglio
Manuela
M
Castiglione-Gertsch
Monica
M
Sun
Zhuoxin
Z
Thürlimann
Beat
B
Mauriac
Louis
L
Forbes
John F
JF
Paridaens
Robert
R
Gelber
Richard D
RD
Colleoni
Marco
M
Smith
Ian
I
Price
Karen N
KN
Goldhirsch
Aron
A
D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000209:etiology; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects*; D013629:Tamoxifen / Q000009:adverse effects*; D014230:Triazoles / Q000009:adverse effects*
D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole