Key result
Adjuvant letrozole resulted in more grade 3 to 5 cardiac adverse events than tamoxifen (2.4% vs 1.4%; P=0.001), but fewer overall thromboembolic events (1.7% vs 3.9%; P<0.001).
Why the study?
Does letrozole compared to tamoxifen alter the risk of cardiovascular adverse events in postmenopausal women with receptor-positive early breast cancer?
RCT (n=8,028)
Double-blind
randomly assigned
Yes
Does letrozole compared to tamoxifen alter the risk of cardiovascular adverse events in postmenopausal women with receptor-positive early breast cancer?
Absolute Event Rate: 2.4% vs 1.4%
p-value: p=0.001
In postmenopausal women with early breast cancer, adjuvant therapy with letrozole is associated with a higher risk of severe cardiac adverse events, while tamoxifen is associated with a higher risk of thromboembolic events.
Balancing cardiac versus thromboembolic risks guides adjuvant endocrine therapy selection; confirms differential safety profiles in postmenopausal early breast cancer.
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.
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Mouridsen et al. (2007) conducted an RCT in receptor-positive early breast cancer (n=8,028). Letrozole vs. Tamoxifen was evaluated on grade 3 to 5 cardiac adverse events (p=0.001). Adjuvant letrozole resulted in more grade 3 to 5 cardiac adverse events than tamoxifen (2.4% vs 1.4%; P=0.001), but fewer overall thromboembolic events (1.7% vs 3.9%; P<0.001).
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