PMID- 17998546
OWN - NLM
STAT- MEDLINE
DCOM- 20071231
LR  - 20220330
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 25
IP  - 36
DP  - 2007 Dec 20
TI  - Cardiovascular adverse events during adjuvant endocrine therapy for early breast 
      cancer using letrozole or tamoxifen: safety analysis of BIG 1-98 trial.
PG  - 5715-22
AB  - PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
FAU - Mouridsen, Henning
AU  - Mouridsen H
AD  - Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen, Denmark. 
      henning.mouridsen@rh.hosp.dk
FAU - Keshaviah, Aparna
AU  - Keshaviah A
FAU - Coates, Alan S
AU  - Coates AS
FAU - Rabaglio, Manuela
AU  - Rabaglio M
FAU - Castiglione-Gertsch, Monica
AU  - Castiglione-Gertsch M
FAU - Sun, Zhuoxin
AU  - Sun Z
FAU - Thurlimann, Beat
AU  - Thurlimann B
FAU - Mauriac, Louis
AU  - Mauriac L
FAU - Forbes, John F
AU  - Forbes JF
FAU - Paridaens, Robert
AU  - Paridaens R
FAU - Gelber, Richard D
AU  - Gelber RD
FAU - Colleoni, Marco
AU  - Colleoni M
FAU - Smith, Ian
AU  - Smith I
FAU - Price, Karen N
AU  - Price KN
FAU - Goldhirsch, Aron
AU  - Goldhirsch A
LA  - eng
SI  - ClinicalTrials.gov/NCT00004205
GR  - CA-75362/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071112
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Nitriles)
RN  - 0 (Triazoles)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 7LKK855W8I (Letrozole)
SB  - IM
MH  - Antineoplastic Agents, Hormonal/adverse effects
MH  - Breast Neoplasms/*drug therapy
MH  - Cardiovascular Diseases/etiology
MH  - Chemotherapy, Adjuvant/adverse effects
MH  - Female
MH  - Humans
MH  - Letrozole
MH  - Middle Aged
MH  - Nitriles/*adverse effects
MH  - Tamoxifen/*adverse effects
MH  - Triazoles/*adverse effects
EDAT- 2007/11/14 09:00
MHDA- 2008/01/01 09:00
CRDT- 2007/11/14 09:00
PHST- 2007/11/14 09:00 [pubmed]
PHST- 2008/01/01 09:00 [medline]
PHST- 2007/11/14 09:00 [entrez]
AID - JCO.2007.12.1665 [pii]
AID - 10.1200/JCO.2007.12.1665 [doi]
PST - ppublish
SO  - J Clin Oncol. 2007 Dec 20;25(36):5715-22. doi: 10.1200/JCO.2007.12.1665. Epub 
      2007 Nov 12.