Lin Ying, Liu Jianlun, Zhang Xiaohua, Li Li, Hu Rui, Liu Jian, Deng Yongchuan, Chen Dedian, Zhao Yangbing, Sun Shengrong, Ma Rong, Zhao Ying, Liu Jinping, Zhang Yang, Wang Xijing, Li Yafen, He Pingqing, Li Enxiao, Xu Zheli, Wu Yaqun, Tong Zhongsheng, Wang Xiaojia, Huang Tao, Liang Zhongxiao, Wang Shui, Su Fengxi, Lu Yunfei, Zhang Helong, Feng Guosheng, Wang Shenming
Department of Surgery, Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Cancer Sci. 2014 Sep;105(9):1182-8. doi: 10.1111/cas.12474. Epub 2014 Sep 18.
Tamoxifen and anastrozole are widely used as adjuvant treatment for early stage breast cancer, but their hepatotoxicity is not fully defined. We aimed to compare hepatotoxicity of anastrozole with tamoxifen in the adjuvant setting in postmenopausal breast cancer patients. Three hundred and fifty-three Chinese postmenopausal women with hormone receptor-positive early breast cancer were randomized to anastrozole or tamoxifen after optimal primary therapy. The primary end-point was fatty liver disease, defined as a liver-spleen ratio <0.9 as determined using a computed tomography scan. The secondary end-points included abnormal liver function and treatment failure during the 3-year follow up. The cumulative incidence of fatty liver disease after 3 years was lower in the anastrozole arm than that of tamoxifen (14.6% vs 41.1%, P < 0.0001; relative risk, 0.30; 95% CI, 0.21-0.45). However, there was no difference in the cumulative incidence of abnormal liver function (24.6% vs 24.7%, P = 0.61). Interestingly, a higher treatment failure rate was observed in the tamoxifen arm compared with anastrozole and median times to treatment failure were 15.1 months and 37.1 months, respectively (P < 0.0001; HR, 0.27; 95% CI, 0.20-0.37). The most commonly reported adverse events were 'reproductive system disorders' in the tamoxifen group (17.1%), and 'musculoskeletal disorders' in the anastrozole group (14.6%). Postmenopausal women with hormone receptor-positive breast cancer receiving adjuvant anastrozole displayed less fatty liver disease, suggesting that this drug had a more favorable hepatic safety profile than tamoxifen and may be preferred for patients with potential hepatic dysfunction.
他莫昔芬和阿那曲唑被广泛用作早期乳腺癌的辅助治疗药物，但其肝毒性尚未完全明确。我们旨在比较绝经后乳腺癌患者辅助治疗中阿那曲唑与他莫昔芬的肝毒性。353名中国绝经后激素受体阳性早期乳腺癌女性在接受最佳初始治疗后被随机分为阿那曲唑组或他莫昔芬组。主要终点为脂肪肝疾病，定义为计算机断层扫描测定的肝脾比<0.9。次要终点包括3年随访期间的肝功能异常和治疗失败。3年后，阿那曲唑组脂肪肝疾病的累积发生率低于他莫昔芬组（14.6%对41.1%，P<0.0001；相对风险，0.30；95%CI，0.21 - 0.45）。然而，肝功能异常的累积发生率无差异（24.6%对24.7%，P = 0.61）。有趣的是，与阿那曲唑组相比，他莫昔芬组观察到更高的治疗失败率，治疗失败的中位时间分别为15.1个月和37.1个月（P<0.0001；HR，0.27；95%CI，0.20 - 0.37）。最常报告的不良事件在他莫昔芬组为“生殖系统疾病”（17.1%），在阿那曲唑组为“肌肉骨骼疾病”（14.6%）。接受辅助阿那曲唑治疗的绝经后激素受体阳性乳腺癌女性脂肪肝疾病较少，表明该药物的肝脏安全性优于他莫昔芬，对于有潜在肝功能障碍的患者可能更适用。
