Departments of Pathology, Surgery, Special Gynecology, and Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Clin Cancer Res. 2011 Dec 15;17(24):7828-34. doi: 10.1158/1078-0432.CCR-11-1846. Epub 2011 Oct 13.
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).
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 Study Group 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.
Patients with a high Ki67 expression (394/1,587; 23%) had a significantly shorter RFS (adjusted HR for recurrence = 1.90, 95% CI: 1.37-2.64, P = 0.0001) and OS (adjusted HR for death = 1.78, 95% CI: 1.18-2.70, P = 0.006). In women with breast tumors expressing medium or high ER levels (n = 1,438), the interaction between Ki67 and adjuvant endocrine treatment was significant for RFS (P = 0.03). TAM followed by ANA was superior to TAM alone in patients with low Ki67 (adjusted HR = 0.53, 95% CI: 0.34-0.83, P = 0.005) but not in high Ki67 disease (adjusted HR = 1.18, 95% CI: 0.66-1.89, P = 0.68).
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.
评估 Ki67 表达在接受辅助他莫昔芬（TAM）单药治疗或 TAM 序贯阿那曲唑（ANA）治疗的绝经后激素受体阳性早期乳腺癌患者中的预测价值。
对奥地利乳腺癌和结直肠癌研究组试验 8 前瞻性随机分组的绝经后内分泌敏感乳腺癌患者的全组织切片进行 Ki67 免疫组化检测，这些患者接受了 5 年 TAM 治疗或 2 年 TAM 序贯 3 年 ANA 治疗。Ki67 表达既作为连续变量，也作为低（≤10%）和高（>10%）的二分变量进行评估。使用 Cox 模型调整临床和病理参数来分析无复发生存（RFS）和总生存（OS）。
Ki67 高表达（394/1587；23%）的患者 RFS 明显更短（复发风险比[HR]为 1.90，95%CI：1.37-2.64，P=0.0001），OS 也更短（死亡风险比[HR]为 1.78，95%CI：1.18-2.70，P=0.006）。在表达中/高 ER 水平的乳腺癌患者（n=1438）中，Ki67 和辅助内分泌治疗之间的交互作用对 RFS 有显著影响（P=0.03）。与 TAM 单药治疗相比，低 Ki67 患者中 TAM 序贯 ANA 治疗更优（调整 HR=0.53，95%CI：0.34-0.83，P=0.005），但在高 Ki67 疾病中无显著差异（调整 HR=1.18，95%CI：0.66-1.89，P=0.68）。
TAM 序贯 ANA 治疗优于 TAM 单药治疗，特别是在中/高 ER 表达、低增殖的绝经后乳腺癌患者中。
