Lewis-Wambi Joan S, Jordan V Craig
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Breast Dis. 2005;24:93-105. doi: 10.3233/bd-2006-24108.
Endocrine therapy that targets the estrogen receptor (ER) is a standard of care for the treatment of postmenopausal women with ER-positive breast cancer. The selective ER modulator (SERM) tamoxifen has been in use for the treatment of advanced breast cancer for more than 30 years and is currently a treatment option for all stages of ER-positive disease. Tamoxifen blocks the action of estrogen by binding to the ER, and possesses both ER-agonist and antagonist properties. Unfortunately, long-term use of tamoxifen is associated with several important concerns including an increased risk of endometrial cancer and thromboembolic complications. In addition, many patients who initially respond to tamoxifen eventually relapse with resistant disease. New treatment approaches are therefore required. A number of alternative SERMs have been tested as substitutes for tamoxifen. These include; toremifene, droloxifene, idoxifene, and keoxifene. Unfortunately, the SERMs have not proved to be more effective than tamoxifen for the treatment of advanced breast cancer and have shown a high level of cross-resistance with tamoxifen. The subsequent development of the aromatase inhibitors (AIs) is an important therapeutic advance by creating a "no estrogen" environment. Another approach is the development of pure antiestrogens. Fulvestrant is a novel ER antagonist that destroys the ER and its signaling pathway and is not associated with tamoxifen-like agonist effects. It produces high response rates compared with other SERMs and is not cross-resistant to tamoxifen or aromatase inhibitors and is equally as effective as the AI anastrozole in the treatment of postmenopausal women with advanced breast cancer who have progressed on prior adjuvant tamoxifen therapy. This review article discusses the significant and continuing value of SERMs for the treatment of postmenopausal ER-positive breast cancer.
针对雌激素受体（ER）的内分泌治疗是绝经后ER阳性乳腺癌治疗的标准方法。选择性ER调节剂（SERM）他莫昔芬已用于治疗晚期乳腺癌30多年，目前是ER阳性疾病各阶段的一种治疗选择。他莫昔芬通过与ER结合来阻断雌激素的作用，兼具ER激动剂和拮抗剂特性。不幸的是，长期使用他莫昔芬存在一些重要问题，包括子宫内膜癌风险增加和血栓栓塞并发症。此外，许多最初对他莫昔芬有反应的患者最终会出现耐药性疾病复发。因此需要新的治疗方法。一些替代的SERM已作为他莫昔芬的替代品进行了测试。这些包括：托瑞米芬、屈洛昔芬、艾多昔芬和凯昔芬。不幸的是，这些SERM在治疗晚期乳腺癌方面并未证明比他莫昔芬更有效，并且与他莫昔芬表现出高度交叉耐药性。芳香酶抑制剂（AI）的后续开发通过创造“无雌激素”环境取得了重要的治疗进展。另一种方法是开发纯抗雌激素药物。氟维司群是一种新型ER拮抗剂，可破坏ER及其信号通路，且不具有类似他莫昔芬的激动剂作用。与其他SERM相比，它产生的缓解率较高，与他莫昔芬或芳香酶抑制剂无交叉耐药性，在治疗既往接受辅助他莫昔芬治疗后病情进展的绝经后晚期乳腺癌女性方面与AI阿那曲唑同样有效。这篇综述文章讨论了SERM在治疗绝经后ER阳性乳腺癌方面的重大且持续的价值。
