Internal endocrine therapy of breast cancer

Additive endocrine therapy of breast cancer was first initiated by androgen treatment through intramuscular administration which proved to be effective in about 25% of trial cases. It was followed by another trial of massive administration of estrogens mainly to patients of more than 60 years of age, and this showed a similar efficacy. Under these circumstances, additive endocrine therapy's position was established as a special therapy for advanced breast cancer. Breast cancer patients have a considerably longer period of progress after disease recurrence than in other types of cancer, so oral androgens were developed for treating recurrent breast cancer patients at home. However, the side effects of androgens (e.g., virilization, hepatic disorders) presented problems with Long-term administration. Since then more androgens with less side effects have been developed which have contributed to the remarkable progress of androgen therapy. On the other hand, recently an anti-estrogen was found which specifically antagonizes estrogen and has few side effects. Additive endocrine therapy's reputation has improved with the emergence of this anti-estrogen agent. Another study has also been started on a progesterone agent which is completely different from conventional sex hormone agents. Anti-estrogen agent is widely accepted for post-operative adjuvant endocrine therapy of breast cancer taking over as the conventional post-operative adjuvant chemotherapy, and also as a partner of chemo-endocrine therapy.     

乳腺癌新辅助内分泌治疗的研究进展

目的:通过文献复习总结目前乳腺癌新辅助内分泌治疗研究的新进展,探讨目前乳腺癌新辅助内分泌治疗研究中的问题及未来发展趋势.方法:应用HighWire、PubMed及CNKI期刊全文数据库检索系统,以"乳腺癌、他莫昔芬、芳香化酶抑制荆和新辅助内分泌治疗"为关键词,检索2000-2010年的相关文献,共检索到英文文献526条.纳入标准:1)乳腺癌的新辅助内分泌治疗.2)他莫昔芬在新辅助内分泌治疗中的应用;3)芳香化酶抑制剂在新辅助内分泌治疗的应用.4)乳腺癌新辅助内分泌治疗综合评价.根据纳入标准,符合分析的文献21篇.结果:乳腺癌新辅助内分泌治疗是最近几年才提出的一种乳腺癌治疗手段,对于雌孕激素受体阳性乳腺癌患者的辅助治疗较化疗有独特的优势.但新辅助内分泌治疗目前尚未成为乳腺癌的常规治疗方法.结论:新辅助内分泌治疗相关的治疗适用对象、治疗药物的选择、用药周期和剂量、疗效评估等多个内容目前仍处于探索阶段.     

乳腺癌新辅助内分泌治疗

随着内分泌治疗药物的发展,新辅助内分泌治疗成为近年来乳腺癌研究的又一热点.大量试验证明,新辅助内分泌治疗能降低肿瘤分期,提高乳腺癌的局部控制率,进一步提高保乳手术率,其中第3代芳香化酶抑制剂的疗效可能优于三苯氧胺.     

乳腺癌新辅助内分泌治疗

新辅助化疗已是局部晚期乳腺癌的规范疗法，但对难以耐受化疗毒副反应的老年人局部晚期乳腺癌则是一治疗难题。文献资料显示，新辅助内分泌治疗是一有效方法，且患者易耐受。从新辅助内分泌治疗的总有效率和保乳手术率看，第三代芳香化酶抑制剂（第三代AI）效果明显优于他莫昔芬。新辅助内分泌治疗为绝经后ER（＋）和／或PgR（＋）的局部晚期或肿瘤较大的乳腺癌提供了一很好的治疗选择。     

Adjuvant endocrine therapy for breast cancer

Endocrine therapy is a critical part of adjuvant therapy in women with hormone receptor-positive breast cancer, and has been shown to reduce the risk of recurrence and death from breast cancer. For decades, 5 years of tamoxifen has been the standard treatment. For premenopausal women, it remains so, and we await the results of ongoing trials to define the role of ovarian suppression or ablation with endocrine therapy. If a woman becomes postmenopausal during treatment, consideration should be given to extended adjuvant therapy with an aromatase inhibitor (AI) for another 5 years. In postmenopausal women, trials have shown that AIs are more beneficial than tamoxifen in preventing disease recurrence.They have been compared as upfront treatment for 5 years, as sequential therapy after 2 to 3 years of tamoxifen, and as extended treatment for 5 years after 5 years of tamoxifen. Among the questions still being studied are the optimal duration of extended adjuvant therapy with AIs, how one AI performs compared to another, and whether there is a benefit to intermittent extended adjuvant treatment.     

Neoadjuvant endocrine therapy in breast cancer

The use of endocrine therapy is well established as a primary treatment for locally advanced breast cancer. However, despite the current popularity of neoadjuvant chemotherapy for operable tumours, there is relatively little published evidence for pre-operative endocrine therapy in operable disease, particularly outside of the elderly population. The wider use of aromatase inhibitors (AIs) has encouraged studies that compare the efficacy of AIs with tamoxifen in the neoadjuvant setting, but there remains a lack of comparison of neoadjuvant with adjuvant endocrine therapies. This review discusses the current evidence regarding primary endocrine therapy, along with the factors involved in choosing appropriate patients for neoadjuvant therapy and the current opinions on length of treatment time and measurement of response prior to surgery.     

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。     

乳腺癌的辅助内分泌治疗

内分泌治疗是激素受体阳性乳腺癌患者的重要治疗手段.他莫昔芬、阿那曲唑和卵巢功能抑制剂是乳腺癌内分泌治疗中的最常用药物,针对患者疾病分期和绝经状态的小同,内分泌治疗药物的选择不同.内分泌治疗被证实有很好的疗效的同时,也被证实会产生耐药,mTOR抑制剂、CDK4/6抑制剂和纤维母细胞生长因子受体抑制剂将为内分泌治疗耐药患者带来新的希望.     

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。     

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。     

Sequential endocrine therapy and chemotherapy in metastatic breast cancer: Effects on survival

Summary Follow-up data of 113 patients with stage IV breast cancer treated with the antiestrogen tamoxifen show that the duration of remission is in average in excess of 21 months with a median of 16 months. Survival from start of antiestrogen therapy was significantly longer in patients who responded to tamoxifen, in those with dominant site of disease in the soft tissue, and in those with less extensive metastatic involvement. Overall survival from onset of metastasis was also much longer in patients who had responded to tamoxifen than in those who had failed (median of 52 and a half months vs 23 months). Hypophysectomy and androgen therapy used sequentially after antiestrogen each induced further remissions in almost half of the patients with a median duration of 16 months and 10 months respectively. Five drug chemotherapy used in most patients after maximum benefit had been obtained with endocrine therapy induced remissions in two-thirds of the patients with a median duration of 8 months. Adriamycin used sequentially as a single agent induced significant further palliation in almost half of the patients with a median duration of 4 and a half months. We conclude that sequential endocrine therapy and chemotherapy is highly effective in the treatment of stage IV breast cancer and offers prolonged survival to patients with hormone responsive tumors. Address for reprints: Dr. Andrea Manni, University Hospitals of Cleveland, 2074 Abington Road, Cleveland, OH 44106.     

Controversies in endocrine therapy for breast cancer

Major advances have been made in the treatment of postmenopausal women with hormone-sensitive breast cancer. Although tamoxifen has been the standard endocrine therapy for the past twenty years, the development of a third generation of aromatase inhibitors (Als), which effectively inhibit estrogen synthesis in extragonadal sites, gives us a wider range of choices in endocrine therapy. However, many questions remain with respect to the optimal use of Als. Differences between Als and tamoxifen as well as non-steroidal and steroidal Als in their long-term adverse effects on bone demineralization and lipid metabolism are only starting to emerge. The preferable orders for use of non-steroidal and steroidal Als, Als and pure anti-estrogen in patients with metastatic disease are emerging subjects to be examined, following several studies that showed non-cross reactivity between these types of drug. Neo-adjuvant endocrine therapy is now attempting to apply breast conserving surgery in larger numbers of elderly patients who are not suitable for neo-adjuvant chemotherapy. Moreover, many investigators are currently searching for surrogate markers in neo-adjuvant endocrine treatment that can predict the responsiveness and prognosis with adjuvant endocrine therapy. Further research concomitant with clinical trials may lead to a more reliable endocrine therapy modality in the treatment of breast cancer.     

Neoadjuvant endocrine therapy in primary breast cancer

Neoadjuvant chemotherapy has been employed increasingly in operable breast cancer during recent years. Several randomized trials showed that the chances of breast conserving therapy are being enhanced, and that survival was not compromised by primary systemic therapy compared to adjuvant treatment. Apart from the surgical advantages of tumor downstaging and breast conservation, therapy upfront might offer the chance to predict subsequent response of an individual patient to a given agent in the adjuvant setting. Furthermore, by investigating pre- and posttreatment tumor specimens, the neaodjuvant setting might help to evaluate new predictive biological markers, assess biologic effects of new treatments, and gain insight into molecular mechanisms. For postmenopausal patients with receptor-positive disease who cannot tolerate the toxicities of chemotherapy regimens or are not eligible for immediate surgery, endocrine treatment is emerging as an attractive alternative in the neoadjuvant setting. The new third-generation aromatase inhibitors letrozole and anastrozole have been compared to tamoxifen in 3 well-designed randomized neoadjuvant phase III trials (PO24, IMPACT, and PROACT). These studies showed significantly higher response rates for letrozole than for tamoxifen, and comparable ones for anastrozole. Thus, the primary use of an aromatase inhibitor seems a feasible and safe treatment option for postmenopausal women with early-stage breast cancer who do not wish to or are unable to undergo immediate surgery or preoperative chemotherapy. Further neoadjuvant endocrine trials should help us to elucidate the cross-talk between the different signal transduction pathways and their role in endocrine resistance.     

Evidence-based neoadjuvant endocrine therapy for breast cancer

Breast cancer is the most common malignancy among women in Western countries. The management of patients with nonmetastatic breast cancer with primary endocrine therapy has evolved dramatically in the past decade. Neoadjuvant treatment has been used to turn inoperable tumors into operable tumors and also to downstage tumors. Hormone receptor-positive breast tumors exposed to neoadjuvant chemotherapy have lower rates of pathologic complete response than hormone receptor-negative tumors. Recently, clinical trials showed an increased response rate and a higher rate of breast-conserving surgery with aromatase inhibitors compared with tamoxifen. Exploratory data suggest that predictive markers of response include a higher estrogen receptor expression level and a negative HER2 status. With the introduction of "biologic" agents and surrogate markers like Ki-67, several studies are evaluating which patients are more likely to respond to preoperative hormonal agents. This review summarizes recent data on neoadjuvant endocrine therapy for breast cancer and the implication of predictive markers of response into clinical practice and future research.     

乳腺癌内分泌治疗的进展

内分泌治疗是激素受体阳性乳腺癌综合治疗的重要组成部分,其疗效已得到广泛的认可.随着新的内分泌药物的出现,乳腺癌的内分泌治疗也取得了新的进展.目前,三苯氧胺对绝经前患者仍是内分泌治疗的标准用药,但对绝经后患者应用芳香化酶抑制剂会有更大的效益.芳香化酶抑制剂及药物去势等多个大型的临床研究还正在进行并备受关注.本文概述乳腺癌的内分泌治疗并着重介绍近期的进展.