Fewer Distant Recurrences With Letrozole: BIG 1-98

BERNE, Switzerland—Using the aromatase inhibitor letrozole (Femara) in postmenopausal hormone-receptor-positive breast cancer patients resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factors, researchers for the BIG 1-98 trial reported in the May issue of Annals of Oncology.

In BIG 1-98, patients were randomized to tamoxifen for 5 years, letrozole for 5 years, tamoxifen for 2 years followed by letrozole for 3 years, or letrozole for 2 years followed by tamoxifen for 3 years. Results showed a significant benefit of letrozole on disease-free survival (19% risk reduction). In the current retrospective analysis of 7,707 eligible patients with a median follow-up of 2 years, 285 had an early relapse: 3.1% on letrozole vs 4.4% on tamoxifen. There were 30% fewer distant recurrences in the letrozole group: 87 (2.3%) vs 125 (3.3%) for tamoxifen.

The study examined prognostic factors of early relapse in an attempt to aid in treatment choices while awaiting definitive BIG 1-98 results on sequential therapy vs upfront letrozole.The following factors significantly predicted early relapse: four or more positive nodes, either or both ER and PR receptors negative, grade 3 tumor, HER2 overexpression or amplification, tumor larger than 2 cm, treatment with tamoxifen, and vascular invasion.

After controlling for these high-risk factors, letrozole significantly reduced the risk of early relapse, compared with tamoxifen. Multivariate analyses showed that, although not significant, letrozole vs tamoxifen was quantitatively more beneficial in high-risk patients (more than four involved nodes, tumors larger than 2 cm, or tumors with vascular invasion) than in intermediate-risk patients. The authors concluded that letrozole may be a better upfront choice in high-risk patients, while sequential therapy could be reserved for intermediate-risk patients.