Treatment of Estrogen Receptor-Positive Breast Cancer
Treatment of Estrogen Receptor-Positive Breast Cancer
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DOI：
10.2174/092986713804999303
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发表时间：
2013-02-01
影响因子：
4.1
通讯作者：
Basso, S. M. M.
中科院分区：
文献类型：
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作者：
Lumachi, F.;Brunello, A.;Basso, S. M. M.
雌激素受体(ER)的表达是内分泌治疗(ET)潜在反应的主要指标，大约70%的人类乳腺癌(BCS)是激素依赖性和ER阳性的。辅助系统治疗的引入显著提高了术后存活率，减少了疾病复发，特别是在早期BC患者和ER+肿瘤患者中，她们可能单独接受ET或联合细胞毒治疗。佐剂ET目前包括(I)卵巢抑制，(Ii)选择性雌激素受体调节剂(SERM)和下调调节剂，以及(Iii)芳香酶抑制剂(AIs)。在ER+肿瘤患者中，促性腺激素释放激素激动剂联合标准辅助治疗的药物抑制卵巢通常比单独辅助化疗更有效。他莫昔芬是最成熟的SERM，对BC控制和骨代谢有良好的作用，但由于其在其他组织中具有雌激素活性，也有不良影响。出于这些原因，已经开发了其他SERM。Fulvestrant是一种ER下调调节剂，与SERM相比有几个潜在的优势，包括与他莫昔芬相比，它对ER的亲和力增加了100倍，并且在子宫中没有雌激素样的活性。与SERM相比，第三代AIS对芳香酶系统的抑制与晚期BC患者的生存改善有关。对于绝经后ER+BC患者，应进行辅助治疗，既可作为三苯氧胺后的序贯治疗，也可作为前期治疗。评估人工授精作为一线治疗的作用的研究正在进行中，结果令人鼓舞。
Estrogen receptor (ER) expression is the main indicator of potential responses to endocrine therapy (ET), and approximately 70% of human breast cancers (BCs) are hormone-dependent and ER-positive. The introduction of adjuvant systemic therapy led to a significant improvement in post-surgical survival and a reduction in disease relapse, especially in women with early BC and those with ER+ tumors, who may receive ET alone or in combination with cytotoxic therapy. Adjuvant ET currently consists of (i) ovarian suppression, (ii) selective estrogen receptor modulators (SERMs) and down-regulators, and (iii) aromatase inhibitors (AIs). In patients with ER+ tumors pharmacologic ovary suppression with gonadotropin-releasing hormone agonists in combination with standard adjuvant therapy is generally more effective than adjuvant chemotherapy alone. Tamoxifen is the best established SERM, has favorable effects on BC control and bone metabolism, but also has adverse effects due to its estrogenic activity in other tissues. For these reasons, other SERMs have been developed. Fulvestrant is an ER down-regulator with several potential advantages over SERMs, including a 100-fold increase in its affinity for ER compared with tamoxifen and no estrogen-like activity in the uterus. The inhibition of the aromatase system with third-generation AIs is associated with improved survival in patients with advanced BC compared with SERMs. In postmenopausal patients with ER+ BC adjuvant treatment with AIs should be performed, either as sequential treatment after tamoxifen or as upfront therapy. Studies evaluating the role of AIs as first-line therapy are ongoing and the results are encouraging.