三苯氧胺治疗乳腺增生病对照试验的系统评价

目的:评价三苯氧胺治疗乳腺增生病的疗效和安全性.方法:通过对MEDLINE、EMBASE、BIOSIS以及Cochrane图书馆对照试验资料库,中国生物医学文摘数据库的机检和手工检索文献的参考文献,选取采用三苯氧胺和中药治疗乳腺增生病的临床对照试验,进行系统评价.中药的剂型、服用方法、疗程不限.结果:5篇试验,包含3 089名患者符合纳入标准,其中有3篇提到随机分组.合并结果表明,三苯氧胺治疗乳腺增生病有一定疗效,[无效的相对危险度(relative risk,RR)为1.88,95%,可信区间(confidence intervals,CI)为0.22～15.72].试验报告有明显副作用,但能在停药后逐渐消失.结论:根据本系统评价,三苯氧胺治疗乳腺增生病有一定疗效,但有可逆的不良反应.然而,由于试验的方法学质量普遍较低,且可能存在发表偏倚,所以目前尚无足够的证据支持它的疗效和安全性,还需要进一步规范的大样本试验.     

治疗乳腺增生常用药物疗效比较

目的:比较乳腺增生治疗药物的疗效。方法:选择临床诊断为乳腺增生症的患者随机分成四组,分别给予乳癖消、乳康片、平消胶囊、三苯氧胺治疗各100例,对比观察疗效及不良反应。结果:总有效率分别为33%、40%、89%、85%。前三种中药制剂未见明显不良反应,三苯氧胺有不良反应。结果:对于保守治疗的乳腺增生症应根据具体情况,主要选择中药制剂,慎用三苯氧胺。     

平消胶囊联合三苯氧胺治疗乳腺增生

目的:观察平消胶囊与三苯氧胺合用治疗乳腺增生的临床疗效.方法:将520 例乳腺增生患者随机分为治疗组和对照组各260例,对照组单用三苯氧胺治疗,治疗组在对照组相同治疗的基础上加用平消胶囊治疗.结果:治疗组总有效率为90.4%,对照组总有效率为67.7%,两组有显著性差异(P＜0.01).结论:平消胶囊与三苯氧胺合用治疗乳腺增生疗效满意,优于单用三苯氧胺.     

三苯氧胺治疗乳腺增生病635例分析

本文报道用三苯氧胺治疗乳腺增生病635例。年龄20~55岁，其中20~30岁70例（26．77%）；31~40岁306例（48．18％）；41－50岁107例（16．85％）。全部病例均用三苯氧胺治疗，显效540例（85％），有效51例（8％）。三苯氧胺治疗乳腺增生病，副作用少，疗效好，是目前较为理想的药物，值得推广应用。     

三苯氧胺治疗乳腺增生病635例分析

本文报道用三苯氧胺治疗乳腺增生病６３５例。年龄２０￣５５岁，其中２０￣３０岁７０例，３１￣４０岁３０６例，４１￣５０岁１０７例，全部病例均用三苯氧胺治疗，显效５４０例，有效５１例，三苯氧胺治疗乳腺增生病，副作用少，疗效好，是目前较为理想的药物，值得推广应用。     

中重度乳腺腺病中西医治疗的疗效观察

目的：观察中西医结合治疗中、重度乳腺腺病的疗效。方法：对396例中、重度乳腺腺病患者采用小剂量的三苯氧胺10mg，每日1次口服，平消胶囊4粒，每日3次口服，均饭后服用，活血化瘀、软坚散结草药蒸热后撇少许白酒局部热敷。结果：治疗有效率95．2％。结论：三苯氧胺、平消胶囊内服结合中草药热敷治疗重度乳腺腺病患者有较好疗效。     

三苯氧胺、天冬素治疗临床乳腺增生病342例疗效分析

乳腺增生病的病因,普遍认为与体内雌孕激素水平失衡有关。国外报道使用雌激素拮抗剂三苯氧胺(TMX)治疗本病。我院对342例病人,随机分为TMX和TMX加天冬素片两个治疗组,作前瞻性对照研究。     

乳腺癌长期行三苯氧胺治疗对乳腺第二原发癌的影响

对１９８５年１月～１９９０年１２月６年间收治的８７４例女性乳腺癌进行了回顾性分析。发生乳腺第二原发癌的病人共２１例。根据是否应用三苯氧胺治疗将病人分为２组。其中应用三苯氧胺治疗（三苯氧胺组）的病人５２３例，平均随访时间为７．８年（４．５～１０年），三苯氧胺治疗剂量为每天２０ｍｇ，服用时间为２～５年，有８例病人发生乳腺第二原发癌，发生率为１．５％。未用三苯氧胺治疗（对照组）的病人３５１例，平均随访时间为７．０年（５～１０年），有１３例病人发生乳腺第二原发癌，发生率为３．７％。三苯氧胺组的乳腺第二原发癌发生率明显低于对照组。经统计学检验，两组间差异有显著性（Ｐ＜０．０５）。结果提示，三苯氧胺有预防乳腺第二原发癌的作用     

三苯氧胺辅助治疗早期乳癌的对照试验

本文分析(1983年12月31日统计资料)三苯氧胺辅助治疗早期乳癌6年多,中数随访45月的全部对照试验结果.作者共收治乳癌患者1285例,年龄≤75岁。经乳腺全切除术或乳癌根治术后,随机分组。除外不适宜本研究患者,562例服三苯氧胺(10mg,每日2次,服二年或至复发);567例为对照,不作进一步的治疗。结果:三苯氧胺组复发或死亡152例;对照组则为220例(P<1.0001)。三苯氧胺治疗失败率比对照     

瘤块型乳腺增生病例分析

目的 探讨瘤块型乳腺增生病的内分泌治疗的效果。方法 自1995年12月13日至1998年6月31日,对30例,瘤块型乳腺增生患者给予达那唑及三苯氧胺口服三个月为一疗程。结果 疗效显著,副作用仅一过性阴道出血1例,月经推迟及轻度发胖1例。结论 本研究显示,对于瘤块型乳腺增生患者,内分泌治疗,疗效可靠,确为独立重要的治疗手段。     

Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status.

BACKGROUND: Most women with oestrogen receptor (ER) positive primary breast cancer receive adjuvant tamoxifen after surgery. The measurement of tumour biomarkers should allow better selection of patients for such treatment or for therapies such as aromatase inhibitors. PATIENTS AND METHODS: Histopathological blocks of primary breast cancer patients who had been randomized to receive 2-years tamoxifen or no adjuvant therapy in two mature randomised clinical trials were retrieved. Immunohistochemical staining for ER, progesterone receptor (PgR), HER2 and epidermal growth factor receptor (EGFR) was undertaken. The primary endpoint was relapse free survival. RESULTS: 813 patients were included in the study. Benefit from tamoxifen was seen in ER-positive patients [Relative risk (rr) 0.77, ci 0.63-0.93]. ER-negative patients also showed a strong trend to benefit from tamoxifen (rr 0.73, ci 0.52-1.02) which was largely confined to the PgR-positive group. Amongst the ER-positive group, PgR-positive and PgR-negative patients showed similar benefit (rr 0.81; ci 0.65-1.02 and 0.70; ci 0.49-0.99, respectively). Patients positive for HER2 did not benefit significantly (rr 1.14; ci 0.75-1.73) but this group was small. CONCLUSIONS: Measurement of PgR status in ER-negative patients defines a group of patients that benefit from tamoxifen but would be excluded from tamoxifen therapy on the basis of ER status alone. The data are consistent with HER2 positive tumours being resistant to tamoxifen.     

Use of tamoxifen in the treatment of malignant melanoma

BACKGROUND: Tamoxifen has been used in the treatment of patients with metastatic malignant melanoma either as a single agent or, more commonly, in combination with other chemotherapeutic agents. The aim of the current study was to summarize the available clinical evidence on the role of the tamoxifen in different combination chemotherapy regimens because clinical studies including tamoxifen have produced inconclusive results. METHODS: The authors designed a systematic review and metaanalysis of published randomized controlled trials to assess the benefit of tamoxifen added to various single-agent or multiagent chemotherapy or biochemotherapy regimens. RESULTS: Six randomized trials met the inclusion criteria and were analyzed. These 6 trials involved a combined total of 912 patients. Of this number, 455 patients were randomized to receive tamoxifen added to chemotherapy or biochemotherapy regimens and 457 were randomized to receive chemotherapy or biochemotherapy without tamoxifen. The overall response rate was not improved significantly by the addition of tamoxifen to the chemotherapy regimen (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.75-1.82; test for overall effect: P = 0.14). The results were not statistically significant for complete response (OR, 0.64; 95% CI, 0.33-1.25; test for overall effect: P = 0.19). CONCLUSIONS: The current metaanalysis demonstrated that tamoxifen does not improve the overall response rate, complete response rate, or survival rate when administered along with combined chemotherapy regimens. Currently, the strength of evidence does not support the use of tamoxifen in combination with other systemic chemotherapy for the treatment of metastatic melanoma.     

Can molecular markers predict when to implement treatment with aromatase inhibitors in invasive breast cancer?

PURPOSE: Resistance to tamoxifen is linked to overexpression of HER2, and aromatase inhibitors show particular benefit in progesterone receptor (PR)-negative patients. We previously reported reduced survival in patients overexpressing HER1, HER2, and HER3. We now show that both HER1-3 and PR status predicts for early relapse in estrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. EXPERIMENTAL DESIGN: Tissue microarray technology was used to analyze 402 ER-positive tamoxifen-treated patients. Immunohistochemistry using epidermal growth factor receptor, HER2, HER3, HER4, and PR antibodies was done. Kaplan-Meier life table and Cox Regression analysis (log-rank testing of differences in breast cancer-related relapse on tamoxifen) was done. RESULTS: HER1-3 (but not HER4) overexpression predicted for early relapse on tamoxifen (P = 0.0060). PR-negative cases were also significantly more likely to relapse while on tamoxifen (P= 0.017). HER1-3-positive and/or PR-negative patients combined as a "high-risk" group were significantly more likely to relapse on tamoxifen in univariate (P < 0.0001) and Cox's multivariate analysis (P = 0.0069). However, this applied to early relapse on tamoxifen only, as any disease relapse after 3 years of tamoxifen was unrelated to PR/HER status. CONCLUSIONS: We show that HER1-3 and PR status can identify time-dependent de novo tamoxifen resistance with risk declining markedly after 3 years of tamoxifen treatment. These results parallel data from the ATAC and Intergroup Exemastane Study trials which suggest that whereas PR-negative patients derive greater benefit from initial aromatase inhibitor treatment, PR status has no effect on response when given as delayed treatment to those disease free on tamoxifen after 3 years.     

ICI 182,780 (Faslodex): development of a novel, "pure" antiestrogen

BACKGROUND: The nonsteroidal antiestrogen tamoxifen is well established as an effective treatment for patients with breast carcinoma, both for the treatment of metastatic disease and as an adjuvant to surgery for patients with primary breast carcinoma. In addition to exerting antagonistic effects on the estrogen receptor, tamoxifen and its derivatives act as partial agonists on certain tissues. These agonistic effects, for example, endometrial stimulation and stimulation of tumor growth after previous response to tamoxifen, may limit their clinical efficacy. ICI 182,780 (Faslodex) from AstraZeneca (Cheshire, United Kingdom) is a novel, steroidal estrogen antagonist that was designed to be devoid of estrogen agonist activity in preclinical models. METHODS: ICI 182,780 was tested in a large number of in vitro and in vivo preclinical models, and its value was assessed clinically when administered before surgery for breast carcinoma and hysterectomy for benign conditions and after failure of tamoxifen in patients with advanced breast carcinoma. RESULTS: All data indicated that ICI 182,780 is devoid of agonist activity in preclinical models and in clinical trials. It inhibits growth of the breast and endometrium. In animal models, it does not cross the blood-brain barrier and appears to be neutral with respect to lipids and bone. ICI 182,780 down-regulates the estrogen receptor and is active in tamoxifen-resistant breast carcinoma. In a small, Phase II study, durable responses were seen: Phase III clinical trials are in progress comparing ICI 182,780 with anastrozole and tamoxifen in the treatment of patients with advanced breast carcinoma. CONCLUSIONS: ICI 182,780 specifically down-regulates the estrogen receptor and, thus, represents the first of a new class of therapeutic agents. In this report, the authors present the current evidence that distinguishes ICI 182,780 from tamoxifen and related nonsteroidal compounds and establishes ICI 182,780 as the first in a new class of therapeutic agents.     

Review of adjuvant breast cancer therapy in non-menopausal women including early results of medical castration with LH-RH analogs

Three treatment modalities have successively dominated adjuvant therapy of breast cancer in non-menopausal women, namely, castration, chemotherapy and tamoxifen administration. The benefits afforded by each of these modalities seem similar when the treatments are compared indirectly by meta-analysis. Once the anti-tumour action of LH-RH analogues and their reversible action on ovarian function had been established, these analogues were used instead of surgical castration in direct comparisons of the three treatment modalities. Most of the patients in these trials had estrogen and/or progesterone receptor positive tumours. According to the current state-of-the-art and whilst awaiting the final results of ongoing trials, we can conclude that: The survival of surgically castrated patients is the same as that of patients who have received CMF-type chemotherapy. The survival of patients on tamoxifen is the same as that of patients who have received CMF-type chemotherapy if tamoxifen is administered for 5 years. It is lower if tamoxifen is given for only 2 years. In 2 out of 3 trials, patients receiving the combined treatment castration plus tamoxifen had improved recurrence-free survival rates compared to patients on chemotherapy (regardless of whether an anthracyclin was included or not. It is too early to comment on overall survival. Combining castration and chemotherapy seems to be advantageous in patients less than forty and in those in whom chemotherapy has not induced amenorrhea. Combining tamoxifen and chemotherapy markedly decreases the risks of disease recurrence and of death but the high standard deviations recorded mean that this statement has to be tempered. Finally, an arrest of ovarian function by LH-RH analogues that is only temporary apparently does not adversely impinge upon results. This has, however, to be proved in an ad hoc trial and the optimum duration of analogue administration has to be established.     

Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma.

PURPOSE: Randomized studies on tamoxifen treatment of hepatocellular carcinoma (HCC) produced conflicting results. The aim of this study was to assess the efficacy of tamoxifen administration in improving overall survival of patients with advanced HCC. PATIENTS AND METHODS: A total of 420 patients with HCC who were not suitable for surgery or local treatment were randomly assigned between April 1995 and May 2000: 210 in the control group and 210 in the tamoxifen group (20 mg/d orally). Patients with WHO performance status greater than 2, belonging to Child-Pugh class C, or with serum creatinine greater than 130 mumol/L were not eligible. RESULTS: Tolerance was good and the main reported adverse effects were thrombophlebitis (three patients), nausea (two patients), and hot flushes (three patients). Outcome did not differ between the two treatment arms: estimated median survival was 4.8 and 4.0 months in the tamoxifen and in the control groups, respectively (P = .25). Univariate analysis showed significant association of survival with age, Okuda stage, WHO performance status, Child-Pugh class, intrahepatic tumor stage, alpha-fetoprotein serum concentration, and presence of extrahepatic spread, portal vein thrombosis, hepatomegaly, or hepatalgia. In a Cox proportional hazards model we found a significant beneficial effect of tamoxifen on survival in patients belonging to Okuda I or II stages. CONCLUSION: In this large study, tamoxifen did not improve the survival of patients with advanced HCC, but there is a suggestion that patients without major hepatic insufficiency seem to have some survival benefit. New trials involving this specific population are warranted.     

Local relapse in primary breast cancer patients with unexcised positive surgical margins after lumpectomy, radiotherapy and chemoendocrine therapy

Background: Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates. To reduce this risk positive margins are, therefore, usually excised. Systemic treatment with tamoxifen or chemotherapy reduces local recurrence, along with radiotherapy. However, no studies to date have examined the correlation between chemoendocrine treatment, together with radiotherapy, and local relapse in patients with unexcised involved resection margins, having had breast conservation treatment.Patients and methods: The histopathology reports were reviewed of 184 patients who were treated from June 1991 to August 1995 within our randomised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate (2M) ± mitomycin-C (3M) and tamoxifen, used concurrently with radiation following conservation surgical treatment. Histological resection margin was considered positive if ductal carcinoma in situ (DCIS) or invasive carcinoma was present microscopically less than 1mm from the excision margin.Results: Although 38% of patients had unexcised microscopically involved margins, local relapse rate as first site of relapse was only 1.9% after a median follow up of 57 months. There was no difference in distant relapse (P = 0.2) and survival (P = 0.5) between the positive and negative margins groups.Conclusions: The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with radiotherapy. Further clinical trials are required.     

Tamoxifen-induced severe hypertriglyceridemia--report of 3 cases

Tamoxifen, an anti-estrogen, has been used for a long time as an adjuvant therapy in cases of estrogen receptor positive breast cancer. Tamoxifen also demonstrates some weak estrogenic activity. A small increase in serum triglycerides is commonly found after tamoxifen administration. Herein we report 3 cases of sever hypertriglyceridemia due to tamoxifen. Case 1 recovered with tamoxifen withdrawal. Tamoxifen was replaced with toremifene in case 2. The level of triglyceride decreased significantly after the change of agent. Tamoxifen was discontinued and anastrozole administration was started in the third patient. Her triglyceride levels improved. Tamoxifen-induced severe hypertriglyceridemia seen in these patients was an effect of its estrogen action. Anastrozole has been used to treat postmenopausal metastatic breast cancer, and several clinical trials in the adjuvant setting are ongoing. Anastrozole does not affect lipid metabolism. Therefore, anstrozole might be safe for patiens with abnormal triglyceride profiles during tamoxifen treatment. We recommended that a periodic serum triglyceride check is needed for patients treated with tamoxifen.     

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval

On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor–positive early breast cancer.The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS.In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77–0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76–1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole.Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen.     

Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma.

BACKGROUND: Two randomized, double-blind trials have compared tamoxifen 20 mg daily and the selective, nonsteroidal aromatase inhibitor anastrozole 1 mg daily as first-line therapy for advanced breast carcinoma (ABC) in postmenopausal women. The trials were prospectively designed to allow for combined data analyses. METHODS: The combined study population included 1021 postmenopausal women (median age, 67 years [range, 30-92]) with ABC whose tumors were either estrogen and/or progesterone receptor positive or of unknown receptor status. Primary endpoints were time to progression (TTP), objective response, and tolerability. RESULTS: At a median duration of follow-up of 18.2 months, anastrozole was at least equivalent to tamoxifen in terms of median TTP (8.5 and 7.0 months, respectively; estimated hazard ratio [tamoxifen relative to anastrozole], 1.13 [lower 95% confidence level, 1.00]). In a retrospective subgroup analysis, anastrozole was superior to tamoxifen with respect to TTP (median values of 10.7 and 6.4 months for anastrozole and tamoxifen, respectively, two-sided P = 0.022) in patients with estrogen and/or progesterone receptor positive tumors (60% of combined trial population). In terms of objective response, 29.0% of anastrozole and 27.1% of tamoxifen patients achieved either a complete response (CR) or a partial response (PR). Clinical benefit (CR + PR + stabilization of > or = 24 weeks) rates were 57.1% and 52.0% for anastrozole and tamoxifen, respectively. Both anastrozole and tamoxifen were well tolerated. Anastrozole led to significantly fewer venous thromboembolic (P = 0.043; not adjusted for multiple comparisons) events, and vaginal bleeding was reported in fewer patients treated with anastrozole than with tamoxifen. CONCLUSIONS: In postmenopausal women with hormonally sensitive ABC, anastrozole should be considered as the new standard first-line treatment.