Rasmussen BB et al. (2008) Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol 9: 23–28

The Breast International Group (BIG) 1-98 trial has previously found that in postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole markedly improves disease-free survival (DFS) compared with tamoxifen. Now, the BIG 1-98 investigators report that letrozole is superior to tamoxifen for the treatment of ERBB2-positive tumors.

The analysis included 3,533 women with estrogen-receptor-positive tumors, who received 5 years of monotherapy with either letrozole or tamoxifen. Receptor expression was measured by immunohistochemistry, and ERBB2 positivity was confirmed by fluorescence in situ hybridization. DFS was worse in the 239 women with ERBB2-positive tumors than in those with ERBB2-negative tumors (hazard ratio [HR] 2.09, 95% CI 1.59–2.76; P <0.0001). The estimated 4-year DFS was 75% for the group with ERBB2-positive tumors versus 88% for those with ERBB2-negative disease. Compared with tamoxifen, letrozole improved DFS irrespective of ERBB2 status (HR 0.62, 95% CI 0.37–1.03 for ERBB2-positive tumors; HR 0.72, 95% CI 0.59–0.87 for ERBB2-negative tumors). The superiority of letrozole over tamoxifen was not influenced by progesterone-receptor status, either in patients with ERBB2-positive or in those with ERBB2-negative disease.

The authors conclude that letrozole provides a treatment benefit over tamoxifen in postmenopausal women with endocrine-responsive breast cancer, regardless of ERBB2 or progesterone-receptor status.