Division of Medical Oncology, Office of the Scientific Director, E. O. Ospedali Galliera, Genoa, Italy.
Cancer Discov. 2012 Jan;2(1):25-40. doi: 10.1158/2159-8290.CD-11-0248.
The Mammary Prevention 3 (MAP.3) placebo-controlled randomized trial in 4,560 high-risk postmenopausal women showed a 65% reduction in invasive breast cancer with the use of exemestane at 35 months median follow-up. Few differences in adverse events were observed between the arms, suggesting a promising risk:benefit balance with exemestane for use in chemoprevention. Yet, the MAP.3 design and implementation raise concerns regarding limited data maturity and not prospectively including key bone-related and other toxicities as study end points. Exemestane for prevention is juxtaposed against selective estrogen receptor modulators and the other aromatase inhibitors. Additional issues for prevention, including the influence of obesity, alternative dosing, and biomarker use in phase III trials, are addressed.
The recently completed MAP.3 trial of exemestane for breast cancer prevention offers a potential new standard for pharmaceutical risk reduction in high-risk postmenopausal women. In addition to describing key findings from the publication of MAP.3 and related trials, our review undertakes a detailed analysis of the strengths and weaknesses of MAP.3 as well as the implications for future prevention research.
目的：在中位随访 35 个月时，Mammary Prevention 3（MAP.3）安慰剂对照随机试验显示，在 4560 例高危绝经后妇女中，使用依西美坦可使浸润性乳腺癌降低 65%。各治疗组间不良事件的差异较小，提示依西美坦用于化学预防的风险获益比有一定优势。然而，MAP.3 的设计和实施引发了人们对数据成熟度有限以及未前瞻性纳入关键骨相关和其他毒性作为研究终点的担忧。依西美坦在预防中的应用与选择性雌激素受体调节剂和其他芳香酶抑制剂并列。文中还讨论了其他与预防相关的问题，包括肥胖的影响、替代剂量以及在 III 期临床试验中生物标志物的应用。
结论：最近完成的依西美坦预防乳腺癌的 MAP.3 试验为高危绝经后妇女的药物风险降低提供了一个潜在的新标准。除了描述 MAP.3 试验及相关试验的主要发现外，我们的综述还对 MAP.3 的优缺点进行了详细分析，并探讨了其对未来预防研究的影响。
