Dunn Barbara K, Ryan Anne
US National Cancer Institute, Division of Cancer Prevention, USA.
Ann N Y Acad Sci. 2009 Feb;1155:141-61. doi: 10.1111/j.1749-6632.2009.03688.x.
The third-generation aromatase inhibitors (AIs), anastrozole, exemestane, and letrozole are potential agents for preventing estrogen receptor (ER)-positive breast cancer (BC) in high-risk postmenopausal women. No AI has yet been fully evaluated for prevention. Each AI is incorporated into the design of a phase 3 randomized BC prevention trial based on hypothesis-generating contralateral breast cancer (CLBC) data from a corresponding adjuvant trial. Arimidex, tamoxifen alone or in combination (ATAC) pitted anastrozole against tamoxifen for 5 years as "initial adjuvant" therapy, showing at 33.3 months fewer CLBCs with anastrozole versus tamoxifen (odds ratio [OR] 0.42 overall; OR 0.29 ER-positive BCs), offering the hypothesis on which IBIS-II (International Breast Cancer Intervention Study) is based. "High-risk" IBIS-II compares anastrozole to placebo for the primary prevention of BC in 6000 postmenopausal women. IES (Intergroup Exemestane Study) compared exemestane to tamoxifen following 2-3 years of adjuvant tamoxifen in 4742 postmenopausal women with ER-positive BCs. The benefit from "switching" to exemestane in reducing CLBCs (HR 0.44 at 30.6 months) underlies MAP.3 (Mammary Prevention 3), which compares exemestane to placebo for primary BC risk reduction in 4560 postmenopausal women. MA.17 showed reduced CLBC incidence (HR 0.57) at 2.4 years in postmenopausal women with receptor-positive tumors receiving "extended adjuvant" letrozole compared to placebo following 5 years of tamoxifen. The Study of Letrozole and Raloxifene (STELLAR), using as the control raloxifene, the new U.S. standard drug for BC prevention, would complete the trio of AI prevention trials, but STELLAR is currently on hold.
第三代芳香化酶抑制剂（AIs），阿那曲唑、依西美坦和来曲唑，是预防高危绝经后妇女雌激素受体（ER）阳性乳腺癌（BC）的潜在药物。尚无一种AI被充分评估用于预防。基于相应辅助治疗试验中产生假设的对侧乳腺癌（CLBC）数据，每种AI都被纳入了一项3期随机BC预防试验的设计中。阿那曲唑、他莫昔芬单药或联合用药（ATAC）试验将阿那曲唑与他莫昔芬作为“初始辅助”治疗进行了5年对比，结果显示在33.3个月时，阿那曲唑组的CLBCs比他莫昔芬组少（总体优势比[OR]为0.42；ER阳性BCs的OR为0.29），这为国际乳腺癌干预研究（IBIS-II）提供了假设依据。“高危”的IBIS-II在6000名绝经后妇女中，将阿那曲唑与安慰剂进行对比，用于BC的一级预防。国际乳腺癌研究组依西美坦研究（IES）在4742名ER阳性BC的绝经后妇女中，在辅助他莫昔芬治疗2 - 3年后，将依西美坦与他莫昔芬进行对比。在降低CLBCs方面（30.6个月时风险比为0.44），从他莫昔芬“转换至”依西美坦的益处是乳腺预防3（MAP.3）试验的基础，该试验在4560名绝经后妇女中，将依西美坦与安慰剂进行对比，用于降低原发性BC风险。MA.17研究显示，与接受5年他莫昔芬治疗后再使用安慰剂相比，接受“延长辅助”来曲唑治疗的绝经后受体阳性肿瘤妇女在2.4年时CLBC发病率降低（风险比为0.57）。来曲唑与雷洛昔芬研究（STELLAR），将雷洛昔芬作为对照，雷洛昔芬是美国预防BC的新的标准药物，该研究将完成AI预防试验的三部曲，但STELLAR目前已暂停。
