Jakesz Raimund, Jonat Walter, Gnant Michael, Mittlboeck Martina, Greil Richard, Tausch Christoph, Hilfrich Joern, Kwasny Werner, Menzel Christian, Samonigg Hellmut, Seifert Michael, Gademann Guenther, Kaufmann Manfred, Wolfgang Johann
Austrian Breast and Colorectal Cancer Study Group (ABCSG), Vienna Medical University, Vienna General Hospital, Waehringer Guertel 18-20, Vienna A-1090, Austria.
Lancet. 2005;366(9484):455-62. doi: 10.1016/S0140-6736(05)67059-6.
Tamoxifen has been the standard adjuvant treatment for postmenopausal women with hormone-responsive early breast cancer for more than 20 years. However, the third-generation aromatase inhibitor anastrozole has proven efficacy and tolerability benefits compared with tamoxifen when used as initial adjuvant therapy. We investigate whether women who have received a period of adjuvant tamoxifen would benefit from being switched to anastrozole.
We present a combined analysis of data from two prospective, multicentre, randomised, open-label trials with nearly identical inclusion criteria. Postmenopausal women with hormone-sensitive early breast cancer who had completed 2 years' adjuvant oral tamoxifen (20 or 30 mg daily) were randomised to receive 1 mg oral anastrozole (n=1618) or 20 or 30 mg tamoxifen (n=1606) daily for the remainder of their adjuvant therapy. The primary endpoint was event-free survival, with an event defined as local or distant metastasis, or contralateral breast cancer. Analysis was by intention to treat.
3224 patients were included in analyses. At a median follow-up of 28 months, we noted a 40% decrease in the risk for an event in the anastrozole group as compared with the tamoxifen group (67 events with anastrozole vs 110 with tamoxifen, hazard ratio 0.60, 95% CI 0.44-0.81, p=0.0009). Both study treatments were well tolerated. There were significantly more fractures (p=0.015) and significantly fewer thromboses (p=0.034) in patients treated with anastrozole than in those on tamoxifen.
These data lend support to a switch from tamoxifen to anastrozole in patients who have completed 2 years' adjuvant tamoxifen.
二十多年来，他莫昔芬一直是绝经后激素反应性早期乳腺癌女性的标准辅助治疗药物。然而，与他莫昔芬相比，第三代芳香化酶抑制剂阿那曲唑在用作初始辅助治疗时已被证明具有疗效和耐受性优势。我们研究了接受过一段时间辅助性他莫昔芬治疗的女性改用阿那曲唑是否会获益。
我们对两项前瞻性、多中心、随机、开放标签试验的数据进行了合并分析，这两项试验的纳入标准几乎相同。完成2年辅助性口服他莫昔芬（每日20或30毫克）治疗的绝经后激素敏感性早期乳腺癌女性被随机分为两组，一组接受每日1毫克口服阿那曲唑治疗（n = 1618），另一组接受每日20或30毫克他莫昔芬治疗（n = 1606），直至完成剩余的辅助治疗。主要终点是无事件生存期，事件定义为局部或远处转移，或对侧乳腺癌。分析采用意向性分析。
3224例患者纳入分析。在中位随访28个月时，我们注意到阿那曲唑组的事件风险比他莫昔芬组降低了40%（阿那曲唑组发生67起事件，他莫昔芬组发生110起事件，风险比0.60，95%可信区间0.44 - 0.81，p = 0.0009）。两种研究治疗的耐受性均良好。与接受他莫昔芬治疗的患者相比，接受阿那曲唑治疗的患者骨折发生率显著更高（p = 0.015），血栓形成发生率显著更低（p = 0.034）。
这些数据支持在完成2年辅助性他莫昔芬治疗的患者中从他莫昔芬改用阿那曲唑。
