Predictive Biomarkers and Personalized Medicine Adjuvant Sequencing of Tamoxifen and Anastrozole Is Superior to Tamoxifen Alone in Postmenopausal Women with Low Proliferating Breast Cancer

Purpose: To assess the predictive value of Ki67 expression in postmenopausal hormone receptor– positive early-breast cancer patients, who were either treated with adjuvant tamoxifen (TAM) alone or with TAM followed by anastrozole (ANA). Experimental Design: Expression of Ki67 was determined centrally by immunohistochemistry on whole tissue sections of postmenopausal endocrine-responsive breast cancers from patients who had been enrolled in the prospectively randomized Austrian Breast and Colorectal Cancer StudyGroup Trial 8, and had received TAM for 5 years, or TAM for 2 years followed by ANA for 3 years. Ki67 expression was evaluated both as a continuous variable and dichotomized to low ( 10%) and high (>10%). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic parameters. Results: Patients with a high Ki67 expression (394/1,587; 23%) had a significantly shorter RFS (adjusted HR for recurrence1⁄4 1.90, 95% CI: 1.37–2.64, P1⁄4 0.0001) and OS (adjusted HR for death1⁄4 1.78, 95% CI: 1.18–2.70, P1⁄4 0.006). In women with breast tumors expressing medium or high ER levels (n1⁄4 1,438), the interaction between Ki67 and adjuvant endocrine treatment was significant for RFS (P 1⁄4 0.03). TAM followed by ANAwas superior to TAM alone in patients with low Ki67 (adjusted HR1⁄4 0.53, 95%CI: 0.34– 0.83, P 1⁄4 0.005) but not in high Ki67 disease (adjusted HR 1⁄4 1.18, 95% CI: 0.66–1.89, P 1⁄4 0.68). Conclusions: Adjuvant sequencing of TAM and ANA is superior to TAM alone, particularly in postmenopausal women with medium or high ER expressing, low proliferating breast cancer. Clin Cancer Res; 17(24); 7828–34. 2011 AACR.