Baum M, Budzar A U, Cuzick J, Forbes J, Houghton J H, Klijn J G M, Sahmoud T
Lancet. 2002 Jun 22;359(9324):2131-9. doi: 10.1016/s0140-6736(02)09088-8.
In the adjuvant setting, tamoxifen is the established treatment for postmenopausal women with hormone-sensitive breast cancer. However, it is associated with several side-effects including endometrial cancer and thromboembolic disorders. We aimed to compare the safety and efficacy outcomes of tamoxifen with those of anastrozole alone and the combination of anastrozole plus tamoxifen for 5 years.
Participants were postmenopausal patients with invasive operable breast cancer who had completed primary therapy and were eligible to receive adjuvant hormonal therapy. The primary endpoints were disease-free survival and occurrence of adverse events. Analysis for efficacy was by intention to treat.
9366 patients were recruited, of whom 3125 were randomly assigned anastrozole, 3116 tamoxifen, and 3125 combination. Median follow-up was 33.3 months. 7839 (84%) patients were known to be hormone-receptor-positive. Disease-free survival at 3 years was 89.4% on anastrozole and 87.4% on tamoxifen (hazard ratio 0.83 [95% CI 0.71-0.96], p=0.013). Results with the combination were not significantly different from those with tamoxifen alone (87.2%, 1.02 [0.89-1.18], p=0.8). The improvement in disease-free survival with anastrozole was seen in the subgroup of hormone-receptor-positive patients, but not the receptor-negative patients. Incidence of contralateral breast cancer was significantly lower with anastrozole than with tamoxifen (odds ratio 0.42 [0.22-0.79], p=0.007). Anastrozole was significantly better tolerated than tamoxifen with respect to endometrial cancer (p=0.02), vaginal bleeding and discharge (p<0.0001 for both), cerebrovascular events (p=0.0006), venous thromboembolic events (p=0.0006), and hot flushes (p<0.0001). Tamoxifen was significantly better tolerated than anastrozole with respect to musculoskeletal disorders and fractures (p<0.0001 for both).
Anastrozole is an effective and well tolerated endocrine option for the treatment of postmenopausal patients with hormone-sensitive early breast cancer. Longer follow-up is required before a final benefit:risk assessment can be made.
在辅助治疗中，他莫昔芬是绝经后激素敏感性乳腺癌女性的既定治疗方法。然而，它与多种副作用相关，包括子宫内膜癌和血栓栓塞性疾病。我们旨在比较他莫昔芬与单独使用阿那曲唑以及阿那曲唑加他莫昔芬联合使用5年的安全性和疗效结果。
参与者为绝经后浸润性可手术乳腺癌患者，他们已完成初始治疗且有资格接受辅助激素治疗。主要终点为无病生存期和不良事件的发生情况。疗效分析采用意向性治疗。
招募了9366名患者，其中3125名被随机分配接受阿那曲唑治疗，3116名接受他莫昔芬治疗，3125名接受联合治疗。中位随访时间为33.3个月。已知7839名（84%）患者激素受体呈阳性。阿那曲唑组3年无病生存率为89.4%，他莫昔芬组为87.4%（风险比0.83 [95%置信区间0.71 - 0.96]，p = 0.013）。联合治疗组的结果与单独使用他莫昔芬组无显著差异（87.2%，1.02 [0.89 - 1.18]，p = 0.8）。阿那曲唑在激素受体阳性患者亚组中可改善无病生存期，但在受体阴性患者中未观察到。阿那曲唑组对侧乳腺癌的发生率显著低于他莫昔芬组（优势比0.42 [0.22 - 0.79]，p = 0.007）。在子宫内膜癌（p = 0.02）、阴道出血和分泌物（两者p < 0.0001）、脑血管事件（p = 0.0006）、静脉血栓栓塞事件（p = 0.0006）以及潮热（p < 0.0001）方面，阿那曲唑耐受性明显优于他莫昔芬。在肌肉骨骼疾病和骨折方面（两者p < 0.0001），他莫昔芬耐受性明显优于阿那曲唑。
阿那曲唑是治疗绝经后激素敏感性早期乳腺癌患者的一种有效且耐受性良好的内分泌治疗选择。在进行最终的获益 - 风险评估之前，需要更长时间的随访。
