The pure antiestrogen ICI 182780 is more effective in the induction of apoptosis and down regulation of BCL‐2 than tamoxifen in MCF‐7 cells

There is increasing evidence that induction of apoptosis by antihormones is an important mechanism in regard to their growth inhibitory action on hormone dependent tumors. In this report we have compared the efficiency of tamoxifen (Tam) and the pure antiestrogen ICI 182780 (ZM) to induce apoptosis in the estrogen dependent breast cancer cell line MCF7. Clear evidence for induction of apoptosis could be demonstrated after treatment with both antiestrogens. Application of the pure antiestrogen ZM led to a significantly higher induction of apoptosis compared to the partial agonistic compound Tam. The ability of the two compounds to induce apoptosis correlated with their growth inhibitory action. On the molecular level administration of ZM led to a time dependent steady decrease of BCL2 mRNA and protein. Administration of Tam also initially decreased the expression of BCL2. In contrast to ZM treatment, BCL2 expression increased again after 8h of incubation with Tam. After 96h Tam treated cells expressed BCL2 levels nearly as high as untreated cells. In general, ZM decreased BCL2 levels more effectively than Tam. Our results demonstrate that ZM and Tam possess quantitative and qualitative differences in their ability to down regulate BCL2 expression. The higher ability of the pure antiestrogen to down regulate BCL2 expression may explain the superiority of the pure antiestrogen to induce apoptosis and to inhibit the growth of MCF7 cells.     

Successful co‐treatment with LHRH‐agonist for ovarian over‐stimulation and cystic formation in premenopausal tamoxifen exposure

The present study evaluates the potential beneficial effect of cotreatment with LHRHagonist in resolving premenopausal tamoxifen's induced supraphysiological serum 17 estradiol levels and persistent ovarian cysts. Ultrasonographic and serum hormonal evaluations were performed before, during, and following three consecutive injections of long acting LHRHagonist administered to 14 premenopausal breast cancer patients treated with tamoxifen, who had supraphysiological serum 17 estradiol levels and simultaneous persistent ovarian cysts. Within 3 weeks of the first LHRHagonist injection, all patients had menopausal serum estradiol levels. Ovarian cysts completely disappeared within 2 months following the first injection. Following the discontinuation of LHRHagonist cotreatment, serum estradiol levels remained in physiological levels and the ovaries remained a normal size in 64.3% of the patients for 13.3 ± 11.5 months. 28.6% of the patients had a gradual reappearance of high serum estradiol levels and of ovarian cysts, and were, therefore, treated with a second course of LHRHagonist. Following the second course, serum estradiol levels remained in physiological levels and the ovaries remained a normal size for 8–15 months. It is concluded that short duration of cotreatment with long acting LHRHagonist administered to premenopausal breast cancer patients treated with tamoxifen, successfully resolved the tamoxifeninduced supraphysiological serum 17 estradiol levels and the ovarian cysts.affiliated with Sackler Faculty of Medicine, Tel Aviv University     

Randomized trial of diethylstilbestrol vs. tamoxifen in postmenopausal women with metastatic breast cancer. An updated analysis

One hundred fiftyone postmenopausal women with progressive metastatic breast cancer and no prior hormonal therapy were treated with either diethylstilbestrol (DES) or tamoxifen (TAM). One hundred fortythree eligible patients were followed until death or for a minimum of 14.1 years on the DES arm or 16.7 years on the TAM arm. The overall objective response was 42% for DES and 33% for TAM (p=0.31) and the median duration of response was 11.8 months for DES and 9.9 months for TAM (p=0.38). Duration of response and progressionfree survival were not found to be significantly different between DES and TAM (p=0.32 and 0.65, respectively). The median survival was 3.0 years for DES vs. 2.4 years for TAM. The 5year survival was 35% for the DES arm and 16% for the TAM arm. Survival was significantly better for women on DES than for women on TAM (adjusted p=0.039). Review of records did not show any difference in pattern of treatment failure or subsequent treatments in the DES and TAM arms.Treatment with DES was more commonly associated with toxicity such as nausea, edema, vaginal bleeding, and cardiac problems, whereas hot flashes were commonly seen with TAM therapy.The initial treatment with DES is associated with increased survival. The basis of this survival advantage is not known. TAM still is the preferred agent in the treatment of metastatic breast cancer, but this trial underscores the fact that estrogens have activity and remain in the armamentarium for treatment of selected patients with metastatic breast cancer.     

Quality of life and adjuvant systemic therapy for early-stage breast cancer

Adjuvant chemotherapy and hormonal therapy reduce the risk of recurrence and death due to breast cancer, but often at considerable cost to the health-related quality of life (HRQL) of patients. The short-term effects of chemotherapy on HRQL are well known and are accepted by most patients for modest gains in survival. The long-term effects of chemotherapy-induced menopause and hormonal therapy on HRQL are poorly recognized. Vasomotor symptoms and altered sexual function are common, distressing and inadequately treated. HRQL information is helpful in describing likely effects of adjuvant treatment, facilitating informed decision-making, identifying health problems to guide research into potential solutions, guiding treatment strategies for interventions with equivalent survival and guiding resource allocation. New technologies will make HRQL information increasingly available for individual patient care.     

Cognitive dysfunction in postmenopausal breast cancer patients on aromatase inhibitors

As mortality in breast cancer patients has improved, morbidity of treatment has become increasingly important. Cognitive dysfunction has been considered as a morbid condition that may possibly result from aromatase inhibitor therapy, the standard treatment in postmenopausal, estrogen/progesterone receptor-positive breast cancer patients. Chemotherapy has been associated with cognitive dysfunction through neuropsychological testing and neurological functional imaging, but the relationship between estrogen and cognition remains largely unexplained. In focusing on aromatase inhibitor therapy, most of the studies yielding mixed results have been limited by confounders and small numbers of populations studied. This article briefly summarizes the major studies evaluating aromatase inhibitor therapy and cognitive dysfunction while considering new directions in future study design.     

三苯氧胺对绝经期妇女内分泌的影响

目的观察三苯氧胺对鲍经期妇女内分泌的影响，探讨三苯氧胺抗雌激素作用和类雌激素效应的形成机制；方法应用放射免疫法监测39名鲍经期女性乳腺癌患三苯氧胺治疗后血清雌激素浓度的变化；结果鲍经期妇女接受三苯氧胺治疗3个月后血清雌二醇、雌酮、脱氢表雄酮浓度均有不同程度的升高，以雌二醇的升高有显性(P<0．01)；结论三苯氧胺可引起鲍经期妇女血清雌激素浓度的升高，升高的雌激素可能缓解曼年期内分泌紊乱而出现的症状。     

他莫昔芬治疗女性绝经后晚期乳腺癌50例

50例晚期乳腺癌妇女,比较国产和英制的他莫昔芬(tamoxifen)的疗效,剂量为10mg bid口服,疗程均在3mo(月)以上,随访6mo以上。结果表明激素受体检测可指导内分泌治疗取得较高效应,2种药物无显著差异。该药对乳腺癌疗效较高,毒副作用较低,安全性大,口服使用方便,优于其他内分泌治疗方案,可为绝经后晚期老年乳腺癌妇女首选的激素治疗药物。     

柴胡止血液治疗宫内节育器所致子宫出血的临床研究附:60例病例报告

目的：观察柴胡止血液与消炎痛等抗前列腺素合成剂对ＩＵＤ所致子宫异常出血的疗效，方法；采用柴胡止血液治疗组与消炎痛等对照组对６０例ＩＵＤ所致子宫异常出血患者进行临床治疗。结果：治疗组临床治愈８例，显效１６例，无效６例，总有效率为８０．００％，对照组临床治愈２例，显效１８例，无效１０例，总有效率为６６．６７％，两组比较无统计学意义（Ｐ〉０．０５）。柴胡止血液在减少置器者月经血量及经期时间方面，与治疗前     

Adjuvant tamoxifen in postmenopausal breast cancer: Preliminary results of a randomized trial

Summary Between May 1978 and March 1982, 179 postmenopausal women with operable breast cancer were randomized to receive either adjuvant tamoxifen, 40 mg daily for three years (TAM group), or no further treatment (controls).The difference in five-year survival rates (61% in the control group, 72% in the TAM group) was not statistically significant. However, there was a significant improvement in disease-free survival in the TAM group (61%) relative to the controls (44%) (p = 0.008). In estrogen receptor positive patients, tamoxifen improved both the disease-free rate (47% controls, 80% with tamoxifen) and the survival rate (63% to 83%). Similar results were observed in progesterone receptor positive patients. In patients that were estrogen receptor negative, tamoxifen modified neither the survival rate nor the disease-free interval.     

乳腺癌辅助内分泌治疗概况

乳腺癌的内分泌治疗是激素依赖型乳腺癌患者重要的辅助治疗之一，分为手术治疗和非手术治疗，近年来手术及放射去势治疗逐渐被药物治疗替代。雌激素受体和／或孕激素受体阳性，是目前临床应用内分泌治疗的重要指标。绝经前后患者内分泌环境的生理差别决定了用药方式的不同。绝经前患者主要抑制卵巢产生雌激素，而绝经后患者主要抑制芳香化酶的功能。本文旨在对乳腺癌患者内分泌常用药物进行简要介绍，并就他莫西芬及芳香化酶抑制剂进行重点介绍。