Evolving uses of hormonal agents for breast cancer therapy
Evolving uses of hormonal agents for breast cancer therapy
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DOI：
10.1016/s0149-2918(02)85158-x
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发表时间：
2002-01-01
影响因子：
3.2
通讯作者：
Cummings, FJ
中科院分区：
文献类型：
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作者：
Cummings, FJ
背景资料：在过去的十年中，已经开发了许多新的激素疗法（HT），包括选择性雌激素受体调节剂（SERM）、芳香酶抑制剂（AI）和雌激素受体（ER）拮抗剂。随着新的临床试验结果的出现，它们在乳腺癌中的应用也在不断发展。虽然他莫昔芬是最广泛使用的乳腺癌HT，最初被批准用于治疗转移性乳腺癌（MBC），但其作为MBC治疗的有效性导致其随后的评估和用作乳腺癌的辅助和降低风险的治疗。然而，他莫昔芬在这些情况下并不普遍有效，并且与罕见的已知毒性相关，例如血栓栓塞和子宫内膜癌的风险增加;因此，寻找更有效和更耐受的HT已经发展。目的：本文综述了支持使用更新的HT作为MBC的初始治疗及其作为辅助，新辅助和化学预防治疗的潜在用途的数据。通过以下检索确定纳入本手稿的文章，仅限于英文出版物：MEDLINE（20世纪60年代中期至2002年1月）、美国肿瘤学会摘要（1997-2001）和圣安东尼奥乳腺癌研讨会摘要（2001和2002）。使用以下检索词：乳腺癌、乳腺癌指南、激素治疗、他莫昔芬、托瑞米芬、来曲唑、阿那曲唑、阿司美坦、醋酸甲地孕酮、氟维司群和ICI 182，780。最近的研究集中在新的药物作为MBC的初始和后续治疗，乳腺癌的辅助或新辅助治疗，和化学预防剂在健康妇女和有导管原位癌（DCIS）病史的妇女中的应用。比较AI与他莫昔芬作为一线MBC治疗的临床试验结果显示，AI与他莫昔芬一样有效或更有效，并且与更少的严重不良事件相关。他莫昔芬仍然是辅助治疗的金标准。然而，正在进行的临床试验比较他莫昔芬与阿那曲唑的初步结果表明，阿那曲唑可能是上级药物。他莫昔芬和AI都已被证明在乳腺癌的新辅助治疗中具有活性。试验结果表明，他莫昔芬对乳腺癌高危患者、其他方面健康的患者、有DCIS病史的患者和小叶原位癌患者的乳腺癌预防有效。尽管他莫昔芬一直是HT治疗乳腺癌的金标准，但正在进行的评估新HT作为初始、新辅助、辅助化学预防疗法可能会大大改变我们目前的临床实践模式。
Background: During the past decade, a number of new hormonal therapies (HTs) have been developed, including the selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and estrogen receptor (ER) antagonists. Their uses in breast cancer are continually evolving as new clinical trial results become available. Although tamoxifen, the most widely used HT for breast cancer, was originally approved for and used in the treatment of metastatic breast cancer (MBC), its effectiveness as MBC therapy led to its subsequent assessment and use as adjuvant and risk-reduction therapy for breast cancer. However, tamoxifen is not universally effective in these settings and is associated with infrequent known toxicities such as increased risk of thromboembolism and endometrial cancer; therefore, a search for more effective and more tolerable HTs has evolved.Objective: This article reviews the data supporting the use of newer HTs as initial treatment of MBC and their potential use as adjuvant, neoadjuvant, and chemopreventive therapies.Methods: Articles for inclusion in this manuscript were identified through the following searches, limited to English-language publications: MEDLINE (mid 1960s to January 2002), American Society of Oncology abstracts (1997-2001), and San Antonio Breast Cancer Symposium abstracts (2001 and 2002). The following search terms were used: breast cancer, breast cancer guidelines, hormonal therapies, tamoxifen, toremifine, letrozole, anastrozole, exemestane, megestrol acetate, fulvestrant, and ICI 182,780.Results: Recent studies have focused on newer agents as initial and subsequent treatment of MBC, adjuvant or neoadjuvant treatments of breast cancer, and chemopreventive agents in both healthy women and women with a history of ductal carcinoma in situ (DCIS). Results of clinical trials comparing AIs with tamoxifen as first-line MBC treatment show that AIs are as effective as, or more effective than, tamoxifen and are associated with fewer serious adverse events. Tamoxifen remains the gold standard for adjuvant therapy. However, preliminary results of ongoing clinical trials comparing tamoxifen with anastrozole suggest that anastrozole may be the superior agent. Both tamoxifen and the AIs have been shown to be active in the neoadjuvant treatment of breast cancer. Trial results have shown that tamoxifen is effective for breast cancer prevention in patients at high risk of developing breast cancer but who are otherwise healthy, patients with a history of DCIS, and patients with lobular carcinoma in situ.Conclusions: Although tamoxifen has been the gold standard of HT for breast cancer, results of ongoing trials assessing the newer HTs as initial, neoadjuvant, adjuvant, and chemopreventive therapies may substantially change our current clinical practice patterns.