芳香化酶抑制剂治疗乳腺癌的临床研究进展

综述芳香化酶抑制剂治疗乳腺癌的作用机制、常见药物和在乳腺癌内分泌治疗中的临床研究进展。     

芳香化酶抑制剂不同顺序治疗转移性乳腺癌的临床研究

背景与目的:第三代芳香化酶抑制剂(aromatase inhibitors,Als)已经成为治疗复发转移乳腺癌的重要手段.因此本研究旨在通过观察甾体类(依西美坦)和非甾体类(阿那曲唑、来曲唑)3种AIs不同顺序治疗复发转移性乳腺癌患者的疗效,探讨其是否存在交叉耐药.方法:回顾分析既往曾经先后用过甾体类和非甾体类AIs,且能够评价疗效和记录疾病进展时间(time to progression,TTP)和(或)治疗失败时间(time to failure,TTF)的80例复发转移性乳腺癌女性患者,全部患者都有雌激素受体(estrogen receptor,ER)和(或)孕激素受体(progesterone receptor,PR)阳性的结果,主要观察终点为临床获益率(clinical benefit rate,CBR).结果:80例患者中,非甾体类阿那曲唑一线解救的CBR是62.5%(15/24)、来曲唑是71.1%(32/45)、甾体类依西美坦为81.8%(9/11).一线甾体类治疗失败后换用非甾体类的CBR为36.4%(4/11),而一线非甾体类治疗失败后,换用甾体类CBR为24.6%(14/57),一线非甾体类失败后,换用另一种非甾体类的CBR为16.7%(2/12).结论:一种AIs失败后换用另一种AIs仍有获益.总体而言,用药越晚,疗效越差,所以尽早选用疗效相对较高的药物是合适的选择.     

他莫昔芬治疗芳香化酶抑制剂耐药的激素受体阳性绝经后转移性乳腺癌患者的临床研究

目的:探讨他莫昔芬治疗芳香化酶抑制剂（AIs）耐药的激素受体阳性（HR+）绝经后转移性乳腺癌（MBC）患者的疗效和安全性。方法:回顾性分析他莫昔芬治疗AIs耐药的30例HR+绝经后MBC患者的临床资料,观察终点为缓解率（RR）、临床获益率（CBR）、疾病进展时间（TTP）和安全性。结果:30例患者中,CR 1例,PR 9例,SD 15例,RR为33.3%,CBR 为50%,中位TTP 6.1个月。23例骨和/或软组织转移患者中,RR为34.8%,CBR为52.2%,中位TTP 7.3个月;7例肝脏和/或肺部转移患者中,RR为28.6%,CBR为42.8%,中位TTP 4.8个月（P=0.019）。不良反应多为面部潮红、阴道干燥、白带增多、阴道出血、恶心、呕吐、腹泻等,均为I、II级。结论:他莫昔芬治疗AIs耐药的HR+绝经后MBC患者安全有效,可改善患者预后。     

第30届圣·安东尼奥乳腺癌研讨会有关芳香化酶抑制剂的应用报道

第30届圣·安东尼奥国际乳腺癌研讨会于2007年12月13日至12月16日在美国德克萨斯州的圣安东尼奥市举行。这是关于乳腺癌专题的一次国际性盛会。本文仅对此次会议上讨论乳腺癌手术后如何合理应用芳香化酶抑制剂的一次卫星会议做一简要介绍。     

芳香化酶抑制剂在绝经后乳腺癌妇女内分泌治疗的策略

在肿瘤治疗领域很少有药物能改变疾病的过程，而第三代芳香化酶抑制剂的出现则改变了乳腺癌的治疗程式。大量随机、前瞻、大样本临床试验结果的出现，使临床医师开始重新认识激素受体阳性和阴性乳腺癌在发病机制、治疗策略和预后方面的不同。     

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。     

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。     

绝经后早期乳腺癌芳香化酶抑制剂治疗相关的骨安全管理中国专家共识

绝经后乳腺癌患者与同龄健康女性相比,骨丢失进一步加速,骨折风险升高,使得病残率和死亡率增加。绝经后乳腺癌患者具有骨丢失的多个危险因素,例如化疗和应用芳香化酶抑制剂（ aromatase inhibitor,AI）治疗等。 AI能够明显改善乳腺癌患者的生存率,但同时也降低雌激素水平,因此,会加速患者的骨丢失,增加骨折风险。随着AI在乳腺癌辅助治疗中的广泛应用,以及乳腺癌患者生存期的延长,应用AI的患者骨丢失的管理也越来越重要。来自全国各地乳腺外科、肿瘤内科、骨科、内分泌科和妇科的多学科知名专家组于2013年讨论并起草了《应用芳香化酶抑制剂的绝经后乳腺癌患者骨丢失和骨质疏松的预防诊断和处理共识》。由于全球临床医师和专家对绝经后乳腺癌骨安全（骨丢失、骨质疏松、骨折）问题的重视和认识的不断加深,且2014年底SOFT研究进一步报道了经卵巢抑制的绝经前乳腺癌患者骨安全问题。因此,中国抗癌协会乳腺癌专业委员会于2015年组织乳腺癌骨安全相关多学科的专家共同讨论对2013年《应用芳香化酶抑制剂的绝经后乳腺癌患者骨丢失和骨质疏松的预防诊断和处理共识》进行修订,并更新为《绝经后早期乳腺癌芳香化酶抑制剂治疗相关的骨安全管理中国专家共识》,以规范绝经后早期乳腺癌骨安全的综合管理。     

500 mg氟维司群治疗既往接受芳香化酶抑制剂治疗的复发转移性乳腺癌患者的回顾性研究

背景与目的：第三代芳香化酶抑制剂(aromatase inhibitors,AI)是绝经后激素受体阳性患者内分泌治疗的常规用药。在既往AI治疗后进展的患者中,500 mg氟维司群存在一定获益。该研究旨在探索500 mg氟维司群在既往接受AI治疗的复发转移性乳腺癌患者中临床实际应用时的疗效及安全性。方法：收集2011年7月—2015年12月复旦大学附属肿瘤医院收治的188例经500 mg氟维司群治疗的既往接受AI治疗的激素受体阳性的复发转移性乳腺癌患者的临床资料。主要观察疗效指标为无进展生存时间(progression-free survival,PFS),次要观察疗效指标包括客观缓解率(objective response rate,ORR)、临床获益率(clinical beneift rate,CBR)以及安全性。结果：中位随访11.3个月,患者的中位PFS为5.9个月(95%CI：4.2~7.5);CBR为40.0%,ORR为3.4%。COX多因素分析提示,患者的PFS与转移部位数目(HR=1.92,95%CI：1.2~2.9,P=0.002)以及既往是否接受转移后化疗(HR=1.52,95%CI：1.0~2.1,P=0.022)有关。6例患者因不良事件停用氟维司群治疗。结论：500 mg氟维司群治疗既往接受AI治疗的复发转移乳腺癌患者的疗效和安全性肯定。     

芳香化酶抑制剂致乳腺癌患者关节痛的病因及防治

芳香化酶抑制剂（AIs）已经广泛用于绝经后雌激素受体阳性的乳腺癌患者的术后辅助治疗.与单独应用他莫昔芬相比,AIs能显著地提高治疗效果,但同时也会带来骨肌系统的副作用,主要包括骨丢失和关节痛,而这已成为导致治疗中断的主要因素.本文对芳香化酶抑制剂导致关节痛的可能病因及治疗进展进行综述.     

药物性卵巢去势联合阿那曲唑治疗绝经前转移性乳腺癌患者的临床研究

 目的　探讨卵巢去势药物戈舍瑞林联合阿那曲唑治疗绝经前转移性乳腺癌患者的临床疗效及预后。方法　回顾性分析44例绝经前晚期乳腺癌患者资料。患者应用阿那曲唑 1 mg,每日1次, 连续口服4周为1个周期;戈舍瑞林 3.6 mg, 每28 d注射1次。所有患者按期评价疗效并分析预后。结果　临床获益率为52.4 %（23／44）,中位疾病进展时间（PFS）为8.3个月（95 % CI：5.3～11.2个月）。按治疗前是否接受过解救化疗分组,未接受解救化疗组（21例）PFS优于接受过解救化疗组（23例）,差异有统计学意义（16.9个月比5.8个月,P＝0.048）。结论　戈舍瑞林联合阿那曲唑对绝经前晚期乳腺癌的疗效肯定,是乳腺癌内分泌治疗的一种有效方案;对于激素依赖型绝经前乳腺癌患者,可以推荐作为一线治疗方案。     

A review of the treatment of endocrine responsive metastatic breast cancer in postmenopausal women

Endocrine therapy is the corner stone treatment for postmenopausal women with hormone receptor-positive metastatic breast cancer (MBC). Besides tamoxifen and many older agents, recently developed endocrine agents for the treatment of MBC include the third generation aromatase inhibitors (AI) – anastrozole, exemestane, letrozole – and the pure oestrogen receptor antagonist fulvestrant. As treatment of breast cancer evolves, both tamoxifen and the AIs are being increasingly used in the adjuvant setting. As such, a significant proportion of patients with hormone receptor-positive MBC will have previously received tamoxifen, an AI or both, as adjuvant treatment. This has changed the metastatic landscape and has an impact on treatment choices for patients with hormone receptor-positive MBC. In this review, we evaluate the available evidence supporting the use of endocrine therapy for the treatment of hormone receptor-positive MBC. Additionally, we consider the effect of prior adjuvant therapy on treatment choice in the metastatic setting and the optimal treatment sequence. Finally, we discuss endocrine-responsive HER2 positive tumours and the ongoing research initiatives which aim to improve outcomes for patients with MBC.     

Fulvestrant for systemic therapy of locally advanced or metastatic breast cancer in postmenopausal women: a systematic review

A systematic review was undertaken to examine all available evidence to develop and support clinical recommendations regarding the use of fulvestrant (Faslodex((R))) as systemic therapy of locally advanced or metastatic breast cancer in postmenopausal women. MEDLINE, EMBASE, American Society of Clinical Oncology Annual Meeting proceedings, San Antonio Breast Cancer Symposia proceedings, and the Cochrane Library were searched through to April of 2008 for reports of randomized controlled trials that met established inclusion criteria. Four relevant Phase III trials were available for inclusion based on established criteria. Three of four Phase III superiority trials found no significant difference between fulvestrant and control, either anastrozole or exemestane, across efficacy and safety endpoints following prior endocrine therapy failure, with two trials further confirming non-inferiority of fulvestrant to anastrozole retrospectively. Fulvestrant can therefore be considered as alternative therapy to anastrozole or exemestane in postmenopausal women with locally advanced or metastatic breast cancer that has recurred on prior adjuvant endocrine therapy or progressed on prior endocrine therapy for advanced disease. There are, however, important methodological concerns across reviewed trials that should be taken under consideration as they may limit the strength of such a conclusion.     

Pre-menopausal breast cancer and aromatase inhibitors: treating a new generation of women

Aromatase inhibitors have revolutionized the treatment of post-menopausal women with hormone receptor positive breast cancer. However, approximately 22% of all cases of breast cancer in North America are diagnosed in women below the age of 50 and a substantial proportion of these women are pre-menopausal. In the pre-menopausal population with hormone receptor positive disease, research on the use of aromatase inhibitors is only beginning to emerge. In this review, the mechanism of action of aromatase inhibitors and the history of endocrine treatment for pre-menopausal breast cancer is briefly presented. Available research to date regarding efficacy and toxicity of aromatase inhibitors in the treatment of pre-menopausal breast cancer and future research directions are also discussed.     

乳腺癌药物卵巢去势新进展

内分泌治疗在激素受体阳性乳腺癌治疗中的地位已受到广泛认可。芳香化酶抑制剂（ Aro-matase inhibitors,AIs）在疗效、耐受性等方面均优于他莫昔芬（Tamoxifen,TAM）。但AIs只可应用于处于绝经状态的乳腺癌患者,因此,对于三苯氧胺耐药或存在禁忌症以及存在高危因素的绝经前患者,卵巢去势无疑为她们打开了一道通往更多、更优选择的大门。手术及放疗去势因其在可逆性、可控性及副作用方面的劣势,而逐渐被药物去势所取代。本文就乳腺癌的药物卵巢去势治疗在内分泌治疗、与化疗比较等方面的新进展做一综述。     

中国早期乳腺癌卵巢功能抑制临床应用专家共识（2016年版）

乳腺癌已经成为威胁中国女性健康的第一大恶性肿瘤,发病率呈逐年递增趋势。中国乳腺癌发病率年增幅速度是世界平均水平的2倍,且年轻化趋势显著,约有60%的患者在诊断时仍为绝经前状态［1］。据统计,中国绝经前女性早期乳腺癌患者中50%~60%激素受体为阳性,辅助内分泌治疗是降低这类患者复发风险的重要手段,如采用他莫昔芬治疗5~10年已经成为绝经前激素受体阳性的早期乳腺癌患者的标准内分泌治疗方式［2-5］。     

Endocrine therapy of metastatic breast cancer

Breast cancer growth and dissemination is regulated by estrogen and different growth factor receptor signalling pathways. The increasing knowledge of the biology of breast cancer regarding the interaction of these signalling pathways provides a tool to understand endocrine therapies response and resistance mechanisms. In patients with slowly progressive disease, no visceral involvement, and minimal symptoms, endocrine therapy could be the strategy of choice, even if the tumor has low estrogen receptor expression. Ovarian suppression and tamoxifen are recommended for premenopausal patients whether aromatase inhibitors are the option for postmenopausal ones. Chemotherapy still remains as the right alternative for hormone unresponsive or resistant patients. This is a review focused on the different strategies and combinations of endocrine therapies for metastatic breast cancer patients considering the potential strategies clinically tested to overcome resistance and the different treatments of choice available for each scenario of disseminated disease.