第3代芳香化酶抑制剂在乳腺癌治疗中的应用

第3代芳香化酶抑制剂是绝经后雌激素受体(ER)阳性乳腺癌内分泌治疗的新进展，对晚期乳腺癌的一线治疗优于三苯氧胺(TAM)，其用于TAM治疗失败之后二线治疗的地位已经明确。对早期乳腺癌的辅助治疗和新辅助治疗比TAM更有效。芳香化酶抑制剂对绝经后女性的远期效应有待进一步研究。     

芳香化酶抑制剂治疗乳腺癌研究进展

第3代芳香化酶抑制剂与其他内分泌制剂相比,具有疗效高、选择性强、毒副作用少等特点,已成为绝经后乳腺癌患者内分泌治疗的主要措施之一.现综述新一代芳香化酶抑制剂的抗肿瘤机制、药理学特性及在绝经后乳腺癌的治疗进展.     

第3代芳香化酶抑制剂在乳腺癌治疗中的应用

第3代芳香化酶抑制剂是绝经后雌激素受体(ER)阳性乳腺癌内分泌治疗的新进展,对晚期乳腺癌的一线治疗优于三苯氧胺(TAM),其用于TAM治疗失败之后二线治疗的地位已经明确.对早期乳腺癌的辅助治疗和新辅助治疗比TAM更有效.芳香化酶抑制剂对绝经后女性的远期效应有待进一步研究.     

芳香化酶抑制剂治疗乳腺癌应注意的几个问题

阐述在中国推广应用芳香化酶抑制剂（AIs）过程中值得注意的问题：必须明确绝经后患者才能应用AIs；主要用于解救治疗，酌情用于辅助治疗，三苯氧胺（TAM）及甲孕酮并没有过时；不能把雌激素水平波动作为换药停药的唯一依据；准确判断HER-2过表达，保证AIs的合理选择；治疗骨转移时，正确理解疗效标准的变化；可以将AIs推广应用到男性乳腺癌的解救治疗；长期应用AIs患者先做骨密度检查，关注骨质疏松对生活质量的影响等。     

芳香化酶抑制剂在乳腺癌治疗中的运用

芳香化酶是绝经后雌激素合成过程中的一个限速酶，而且在乳腺癌组织中为高表达，因此芳香化酶抑制剂（AI）可通过对其抑制作用而控制绝经后乳腺癌的发展。现综述AI的分类、发展、在乳腺癌治疗中的作用机制以及在各期乳腺癌治疗中的应用，并着重介绍第3代AI。     

芳香化酶抑制剂在乳腺癌治疗中的运用

芳香化酶是绝经后雌激素合成过程中的一个限速酶,而且在乳腺癌组织中为高表达,因此芳香化酶抑制剂(AI)可通过对其抑制作用而控制绝经后乳腺癌的发展.现综述AI的分类、发展、在乳腺癌治疗中的作用机制以及在各期乳腺癌治疗中的应用,并着重介绍第3代AI.     

乳腺癌新辅助内分泌治疗进展

 针对局部晚期乳腺癌患者,尤其是绝经后内分泌反应型且不能耐受化疗的群体,新辅助内分泌治疗不失为一种选择方案。第三代芳香化酶抑制剂为绝经后患者首选药物,因其疗效显著优于他莫昔芬。同比新辅助化疗,在病例选择得当的前提下,新辅助内分泌治疗可获得相似的短期获益,由于长时间随访结果较少,总体预后尚不清楚。     

重视芳香化酶抑制剂在乳腺癌治疗中的地位

1896年Beatson应用卵巢切除术开创了乳腺癌内分泌治疗的历史,经过100余年的发展,内分泌治疗已广泛应用于临床.近年来随着抗雌激素类药物、芳香化酶抑制剂和LH-RH类似物相继上市,传统的肾上腺切除、垂体切除术和雄性激素、雌性激素类药物因其不良反应明显而被逐渐淘汰,内分泌治疗正在以新的风貌展示于人类,给乳腺癌患者带来福音.其中芳香化酶抑制剂(aromatase inhibition,AI)的研究异常活跃,新药不断涌现,治疗方向不断拓展,显示出特有的生机和活力.     

乳腺癌内分泌治疗进展

乳腺癌的内分泌治疗是肿瘤综合治疗的重要组成部分之一。30多年来，三苯氧胺（TAM）已成为乳腺癌内分泌治疗的标准药物。第3代芳香化酶抑制剂的研制和开发，使乳腺癌内分泌治疗进入了一个崭新的时期。随着几个大型国际多中心、随机、双盲临床试验结果的不断公布，TAM在乳腺癌内分泌治疗中的金标准地位受到挑战。     

芳香化酶抑制剂治疗乳腺癌研究进展

全文综述了三代芳香化酶抑制剂用于乳腺癌治疗的现状以及最新研究进展。     

Aromatase inhibitors in adjuvant therapy for hormone receptor positive breast cancer: a systematic review

BACKGROUND: A systematic review was undertaken to review the evidence for the use of third-generation aromatase inhibitors (anastrozole, letrozole and exemestane) as adjuvant therapy for post-menopausal women with early-stage, hormone receptor-positive breast cancer and to develop and support recommendations for their use, with regard to three areas: aromatase inhibitors compared to tamoxifen, aromatase inhibitors in sequence with tamoxifen for a total of five years, and aromatase inhibitors given after five years of tamoxifen therapy. METHODS: MEDLINE, EMBASE, American Society of Clinical Oncology and San Antonio Breast Cancer Symposium proceedings, and the Cochrane Library were searched to May 2007 for reports of randomized controlled trials that met the inclusion criteria. RESULTS: Nine randomized controlled trials and one meta-analysis of three of these trials were identified that reported efficacy data. Eight of these trials reported significantly improved disease-free survival in the arms that involved aromatase inhibitors. The meta-analysis reported significantly improved overall survival among all patients, as did one individual trial. One trial of five years letrozole or placebo after five years tamoxifen found improved overall survival among node-positive patients. CONCLUSIONS: Aromatase inhibitors provide an alternative to tamoxifen as adjuvant therapy for post-menopausal, hormone-receptor-positive breast cancer patients. The options include anastrozole and letrozole for five years, as well as anastrozole and exemestane following two to three years of tamoxifen, for a total five years of hormonal therapy. Five years of letrozole should be considered following five years of tamoxifen. Patients receiving aromatase inhibitors should be monitored for changes in bone mineral density and for cardiovascular disease risk factors and outcomes.     

乳腺癌芳香化酶抑制剂治疗的现状与存在问题

当前乳腺癌内分泌治疗的重大进步是新一代芳香化酶抑制剂（AIs）的研发使用。从1998年开始,先后有第二代的兰他隆（福美斯坦）、第三代的弗隆（来曲唑）、瑞宁得（阿那曲唑）、阿诺新（依西美坦）等在我国临床应用,正确的内分泌治疗理念也随之为大家逐渐接受。     

乳腺癌内分泌治疗进展

乳腺癌的内分泌治疗是肿瘤综合治疗的重要组成部分之一。30多年来,三苯氧胺(TAM)已成为乳腺癌内分泌治疗的标准药物。第3代芳香化酶抑制剂的研制和开发,使乳腺癌内分泌治疗进入了一个崭新的时期。随着几个大型国际多中心、随机、双盲临床试验结果的不断公布,TAM在乳腺癌内分泌治疗中的金标准地位受到挑战。     

早期乳腺癌辅助治疗的实践与思考

乳腺癌内科领域的药物治疗涵盖两个内容,其中之一便是无病灶的治疗,即术后辅助治疗.因患者已无具体病灶,且无法明确患者的无病存活和总存活时间,所以无法对辅助治疗进行个体评价,只能根据循证医学的证据,即大型的随机对照研究的结果,来制定我们的辅助治疗方案.     

Aromatase expression and outcomes in the P024 neoadjuvant endocrine therapy trial

Background Expression of aromatase by malignant breast epithelial cells and/or the surrounding stroma implies local estrogen production that could influence the outcome of endocrine therapy for breast cancer. Methods A validated immunohistochemical assay for aromatase was applied to samples from the P024 neoadjuvant endocrine therapy trial that compared tamoxifen and letrozole. The presence of aromatase expression by tumor or stromal cells was correlated with tumor response, treatment induced changes in proliferation index (Ki67), relapse-free survival (RFS) and breast cancer-specific survival (BCSS). Results Tumor and stromal aromatase expression were highly correlated (P = 0.0001). Tumor cell aromatase, as a semi-continuous score, also correlated with smaller tumor size at presentation (P = 0.01) higher baseline ER Allred score (P = 0.006) and lower Ki67 levels (P = 0.003). There was no significant relationship with clinical response or treatment-induced changes in Ki67. However, in a Cox multivariable model that incorporated a post-treatment tumor profile (pathological T stage, N stage, Ki67 and ER status of the surgical specimen), the presence of tumor aromatase expression at baseline sample remained a favorable independent prognostic biomarker for both RFS (P = 0.01, HR 2.3, 95% CI 1.2–4.6 for absent expression) and BCSS (P = 0.008, HR 3.76, 95% CI 1.4–10.0). Conclusions Autocrine estrogen synthesis may be most characteristic of smaller, more indolent and ER-rich breast cancers with lower baseline growth rates. However, response to endocrine treatment may not depend on whether the estrogenic stimulus has a local versus systemic source.     

赫赛汀在乳腺癌新辅助治疗与辅助治疗中的新进展

人源化单克隆抗体赫赛汀（herceptin）是第一个针对HER-2阳性乳腺癌的、以癌基因为靶的治疗药物。多项研究已证明,赫赛汀对治疗转移性乳腺癌有明显效果,单药治疗总有效率在25％左右。据Slamon等的Ⅲ期临床试验报道,将469例HER-2过度表达的女性转移性乳腺癌患者随机分为单用化疗组与化疗＋赫赛汀组,结果赫赛汀提高了肿瘤缓解率,延长了疾病进展时间（TTP））、中位缓解持续时间和整体生存时间。一组Ⅱ期随机对照研究（M77001）证明了赫赛汀联合泰索帝在一线治疗HER-2阳性转移性乳腺癌的地位。     

乳腺癌新辅助内分泌治疗的研究进展及展望

新辅助内分泌治疗（neoadjuvant endocrine therapy,NET）代替新辅助化疗（neoadjuvant chemotherapy therapy,NCT）对于雌激素受体（estrogen receptor,ER）阳性乳腺癌患者而言是一种有效的临床治疗策略,可以使肿瘤降期,从而接受乳腺癌保乳手术并减少术后的辅助化疗。本文旨在就NET的患者选择、NET效果对比、NET持续时间、NET与NCT效果对比及联合使用、NET联合靶向治疗、机会之窗试验、疗效评估预后指标及NET后辅助治疗决策等最新研究进展进行综述。     

Molecular signatures of neoadjuvant endocrine therapy for breast cancer: characteristics of response or intrinsic resistance

Approximately 30% of patients with estrogen receptor (ER) positive breast cancers exhibit de novo or intrinsic resistance to endocrine therapies. The purpose of this study was to define genes that distinguish ER+ resistant from ER+ responsive tumors, prior to the start of hormone therapies. Previously untreated post-menopausal patients with ER+ breast cancers were treated for 4 months in a neoadjuvant setting with the aromatase inhibitor exemestane alone, or in combination with the antiestrogen tamoxifen. Matched pre- and post-treatment tumor samples from the same patient, were analyzed by gene expression profiling and were correlated with response to treatment. Genes associated with tumor shrinkage achieved by estrogen blockade therapy were identified, as were genes associated with resistance to treatment. Prediction Analysis of Microarrays (PAM) identified 50 genes that can predict response or intrinsic resistance to neoadjuvant endocrine therapy of ER+ tumors, 8 of which have been previously implicated as useful biomarkers in breast cancer. In summary, we identify genes associated with response to endocrine therapy that may distinguish ER+, hormone responsive breast cancers, from ER+ tumors that exhibit intrinsic or de novo resistance. We suggest that the estrogen signaling pathway is aberrant in ER+ tumors with intrinsic resistance. Lastly, the studies show upregulation of a “lipogenic pathway” in non-responsive ER+ tumors that may serve as a marker of intrinsic resistance. This pathway may represent an alternative target for therapeutic intervention. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. A commentary to this article is available at .