title: Cardiovascular adverse events during adjuvant endocrine therapy for early breast cancer using letrozole or tamoxifen: safety analysis of BIG 1-98 trial.
abstract: 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.
authors.affiliation: Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen, Denmark. henning.mouridsen@rh.hosp.dk
authors.forename: Henning
authors.initials: H
authors.lastname: Mouridsen
authors.forename: Aparna
authors.initials: A
authors.lastname: Keshaviah
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Manuela
authors.initials: M
authors.lastname: Rabaglio
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Zhuoxin
authors.initials: Z
authors.lastname: Sun
authors.forename: Beat
authors.initials: B
authors.lastname: Thürlimann
authors.forename: Louis
authors.initials: L
authors.lastname: Mauriac
authors.forename: John F
authors.initials: JF
authors.lastname: Forbes
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: Ian
authors.initials: I
authors.lastname: Smith
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: 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*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole