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在芝加哥当地时间6月1日上午的ASCO乳腺癌专场上，来自加拿大蒙特利尔麦吉尔大学及犹太总医院肿瘤外科的专家Richard G.Margolese带来了一项3期试验的口头报告，提示绝经后的导管原位癌（DCIS）的女性在乳腺癌预防方面将有新的选择（摘要号LBA500）。医脉通对此进行了报道。
这项由联邦资助的临床3期试验，在3000多名幸存者中比较了标准的5年他莫昔芬疗法和5年芳香化酶抑制剂阿那曲唑疗法。阿那曲唑组的10年无乳腺癌生存率高于他莫昔芬组（93.5% vs. 89.2%）。
研究的主要作者、来自加拿大蒙特利尔麦吉尔大学及犹太总医院肿瘤外科的专家Richard G. Margolese说道：“好消息是他莫昔芬和阿那曲唑都有效，但是看起来患者对阿那曲唑耐受性更好。当和医生讨论治疗时，患者也要考虑到副作用的差异。”
尽管导管原位癌患者经放射或肿瘤切除后乳腺癌相关死亡不常见，但是DCIS患者发展为浸润性乳腺癌的风险增加。虽然他莫昔芬和芳香化酶抑制剂已经用于防止更高级别进展的乳腺癌复发，但是此项试验是在DCIS患者中第一个比较2种疗法的研究。在该试验中，将3104名绝经后、雌激素受体阳性的DCIS患者随机分为每日他莫昔芬或阿那曲唑治疗组，每种疗法5年。在开始激素疗法之前，所有的患者均接受乳腺肿瘤切除术和放射治疗。
在平均随访8.6年后，他莫昔芬组和阿那曲唑组分别发现114名和84名乳腺癌患者。这包括复发性DCIS和在同侧或者另侧乳腺新出现的乳腺癌（DCIS或浸润性）。阿那曲唑的10年无乳腺癌率高于他莫昔芬组（93.5% vs. 89.2%），而且差异具有统计学意义。
他莫昔芬组因乳腺癌死亡的有8人，阿那曲唑组有5人。两组10年总生存率相当（阿那曲唑组为92.5%；他莫昔芬组为92.1%）。亚组分析显示对于60岁以上的妇女，阿那曲唑可能不优于他莫昔芬。
激素受体阳性的乳腺癌是依靠雌激素而生长的。他莫昔芬和阿那曲唑以不同的方式阻滞雌激素生成信号通路。虽然他莫昔芬阻滞雌激素受体（如使雌激素接近肿瘤细胞），但是阿那曲唑抑制雌激素的合成。
总体上说，这些药物之间的毒副作用没有明显的差异。阿那曲唑的主要副作用就是加剧骨质疏松，这将会增加骨折的风险。的确，阿那曲唑比他莫昔芬导致骨折发生率更高，尽管差异没有统计学意义。另外，他莫昔芬疗法可导致更高的子宫癌的发生率，但是同样的两组差异没有统计学意义。
摘要原文
Background: The primary endpoint of NSABP B-35, a phase III trial comparing 1 mg/day anastrozole to 20 mg/day tamoxifen, each given for 5 years, was breast cancer-free interval (BCFI), defined as the time from randomization to any breast cancer (BC) event including local, regional, or distant recurrence or contralateral disease, invasive or DCIS.
Methods: Postmenopausal women with ER-receptor or PgR-receptor positive (by IHC analysis) DCIS and no invasive BC who had undergone a lumpectomy with clear resection margins were randomly assigned to receive either 20 mg/day tam or 1 mg/day A (blinded) for 5 years. Stratification was by age (<60 v ≥60).
Results: From 1/6/2003 to 6/15/2006, 3,104 pts were entered and randomized (1552 in groups tam and A each). As of 2/28/15, follow-up information was available on 3,083 pts for OS and on 3,077 pts for all other disease-free endpoints, with mean time of follow-up of 8.6 years. There were 198 BCFI events, 114 in the tam group and 84 in the A group (HR, 0.73; p=0.03). 10-year point estimates for BCFI were 89.2% for tam and 93.5% for A. A significant time-by-treatment interaction (p=0.02) indicated that the effect was not evident until later in the study. There was a significant interaction between treatment and age group (p=0.04); benefit of A is only in women <60 years old. As to secondary endpoints, there were 495 DFS events, 260 in the tam group and 235 in the A group (HR, 0.89; p=0.21). 10-year point estimates for DFS were 77.9% for tam and 82.7% for A. There were 186 deaths, 88 in the tam group and 98 in the A group (HR, 1.11; p=0.48). 10-year point estimates for OS were 92.1% for tam, 92.5% for A. There were 8 deaths due to breast cancer in the tam group and 5 in the A group. There were 63 cases of invasive breast cancer in the tam group and 39 in the A group (HR, 0.61; p=0.02). There was a non-significant trend for a reduction in breast second primary cancers with A (HR, 0.68; p=0.07).
Conclusions: Anastrozole provided a significant improvement compared to tamoxifen for BCFI, which was seen later in the study, primarily in women <60 years. Support: CA12027, 37377, 69651, 69974; 180868, 180822, 189867 196067, 114732; AstraZeneca Pharmaceuticals LP.
会议专题》》》2015年ASCO年会专题报道
