New Strategies in Estrogen Receptor-Positive Breast Cancer
New Strategies in Estrogen Receptor-Positive Breast Cancer
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DOI：
10.1158/1078-0432.ccr-09-1823
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发表时间：
2010-04-01
影响因子：
11.5
通讯作者：
Johnston, Stephen R. D.
中科院分区：
文献类型：
--
作者：
Johnston, Stephen R. D.
内分泌治疗显著改善了雌激素受体阳性(ER+)乳腺癌患者的预后。目前佐剂环境中的问题包括内分泌治疗的最佳持续时间，以及使用基于基因阵列的分析方法与ER表达本身进行比较对内分泌反应的准确分子预测。在晚期疾病中，新型选择性雌激素受体拮抗剂(SERM)未能产生影响，尽管纯ER拮抗剂fulvestrant可能有作用，尽管最佳剂量和序列尚不清楚。克服从头开始的或获得性内分泌抵抗对于进一步提高现有内分泌治疗的益处仍然至关重要。最近在了解获得性内分泌抵抗相关的分子生物学方面取得了进展，包括ER和多肽生长因子受体通路之间的适应性“串扰”，如表皮生长因子受体(EGFR)/人表皮生长因子受体2(HER2)。未来正在评估的策略包括将内分泌治疗与生长因子受体或下游信号通路的抑制剂相结合，以治疗或防止对ER+肿瘤起作用的关键耐药通路。临床前实验为这一方法提供了巨大的希望，尽管临床数据仍然参差不齐。通过不同ER+亚型的分子图谱丰富试验招募将变得越来越重要，以最大限度地发挥新药物可能为当前乳腺癌内分泌治疗带来的额外好处。临床癌症研究；16(7)；1979-87。(C)2010年AACR。
Endocrine therapy has led to a significant improvement in outcomes for women with estrogen receptor-positive (ER+) breast cancer. Current questions in the adjuvant setting include the optimal duration of endocrine therapy, and the accurate molecular prediction of endocrine responsiveness using gene array-based assays compared with ER expression itself. In advanced disease, novel selective estrogen receptor antagonists (SERM) have failed to make an impact, although the pure ER antagonist fulvestrant may have a role, albeit optimal dose and sequence remain unclear. Overcoming de novo or acquired endocrine resistance remains critical to enhancing further the benefit of existing endocrine therapies. Recent progress has been made in understanding the molecular biology associated with acquired endocrine resistance, including adaptive "cross-talk" between ER and peptide growth factor receptor pathways such as epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2). Future strategies that are being evaluated include combining endocrine therapy with inhibitors of growth factor receptors or downstream signaling pathways, to treat or prevent critical resistance pathways that become operative in ER+ tumors. Preclinical experiments have provided great promise for this approach, although clinical data remain mixed. Enriching trial recruitment by molecular profiling of different ER+ subtypes will become increasingly important to maximize additional benefit that new agents may bring to current endocrine therapies for breast cancer. Clin Cancer Res; 16(7); 1979-87. (C)2010 AACR.