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。     

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     

乳腺癌长期辅助性三苯氧胺治疗

对６３例激素受体阳性乳腺癌长期辅助性三苯氧胺治疗的疗效、安全性及预防乳腺第二原发癌的作用回顾性分析。可评仨者６１例。总的５年生存率、无瘤生存率分别为６５．６％和５４．５％。小于５０岁、５０岁及以上，绝经前、后，腋淋巴结阳性及阴性者５年生存率分别为５５．７％、７７．８％，５０．３％、７９．１％，６３．６％和８０．０％（各组Ｐ＜０．０５）。１例子宫内膜呈不典型性增生，１例发生对侧乳腺第二原发癌（１．６％）。表明长期辅助性三苯氧胺治疗能提高５年生存率，安全可靠，可预防乳腺第二原发癌，但应警惕子宫内膜癌发生。     

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.     

中西医结合治疗乳腺囊性增生的疗效观察

本院乳腺疾病普查乳腺小叶增生发病率为20％，而囊性增生的占25％，有1－3％的癌变率，我院于1997年1月至1998年12月应用平消胶囊加工三苯氧胺治疗乳腺囊性增生66例，总有效率达97％，取得良好的治疗效果。     

乳腺癌应用电化学合并三苯氧胺治疗（附37例报告）

目的 对乳腺恶性肿瘤不论是原发或复发转移失去手术机会，年老体弱不易手术或不愿接受手术的患者均可采用电化学治疗（ECT）。方法 应用北京原子能科学院研制的WL－A型电化学治疗仪，在肿瘤部位插入阴，阳电极针分别连接到治疗仪通电治疗；11例原发乳腺癌自电化学治疗开口服服三苯氧胺（TAM）三年。结果 本组ECT治疗乳腺恶性肿瘤37例，按国际ECT协会评定疗效的标准；CR26例，PR6例，总有效率为86．3％（CR＋PR32／37）。结论 乳腺癌应用电化学合并三苯氧胺治疗创伤小，操作简单，疗效满意。     

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3089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。     

奥曲肽诱导乳腺肿瘤细胞凋亡的实验研究

目的初步阐明奥曲肽（Ｏｃｔｒｅｏｔｉｄｅ，ＳＭＳ２０１，９９５，商品名：善得定）与乳腺肿瘤细胞凋亡的关系。方法取手术切除的１６例女性乳腺癌标本，制备肿瘤单细胞悬液，加入善得定（０．１μｇ／ｍｌ）和三苯氧胺（１μｇ／ｍｌ），用ＤＮＡ断端标记法（ＴＤＴ法）分析药物及ＥＲ、ＰＲ对乳腺肿瘤细胞凋亡的影响。结果加入善得定４小时后凋亡率为１０．６±６．９％，１８小时为１４．３±８．８％，ＥＲ（＋）ＰＲ（＋）组４小时善得定凋亡率为１４．３±５．７％，１８小时为２０．２±７．１％，加用三苯氧胺后１８小时组凋亡率为２６．３±８．９％，而ＥＲ（－）ＰＲ（－）组４小时善得定组凋亡率为４．４±３．０％，１８小时为６．５±４．０％，加用三苯氧胺后１８小时组凋亡率为８．８±４．１％，与ＥＲ（＋）ＰＲ（＋）组相比有明显差异（Ｐ＜０．０５）。结论善得定可诱导乳腺肿瘤细胞凋亡，且短时间内即可达到一定的凋亡率，善得定对ＥＲ（＋）ＰＲ（＋）的乳腺肿瘤细胞较敏感，而对ＥＲ（－）ＰＲ（－）组则基本无影响，善得定加用三苯氧胺的治疗有望成为乳腺癌患者术后一个新的辅助生物治疗手段     

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。     

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。     

Toremifene and tamoxifen in advanced breast cancer - a double-blind cross-over trial

Summary Toremifene (TOR) is a triphenylethylene derivative related to tamoxifen (TAM). TOR has antitumor activity, not dependent on estrogen receptors, and responses with TOR have been observed in patients with progressive disease during TAM-treatment. To elucidate possible cross-resistance between these two antiestrogens, we compared their anti-tumor activity in a randomized, double-blind, cross-over study.66 postmenopausal women with advanced estrogen receptor positive or unknown breast cancer and a median age of 63 years (range 38-82) were included. Patients were randomized to TAM 40mg/day or TOR 240mg/day. Treatment continued until progressive disease, when cross-over to the alternative treatment was done. The response rate with first line TOR was 29% (95% confidence limits 10–41%) and with TAM 42% (95% confidence limits 25–61%). Response rates and response durations, survival and toxicity were not significantly different between the two treatments. 44 patients progressing on first line TAM or TOR were evaluable for second line TOR or TAM treatment. As no responses were observed, the possibility of overlooking a response rate of 20% or more is less than 1%.In conclusion, this study strongly indicates that TOR and TAM are clinically cross-resistant in patients with advanced breast cancer.     

Oral high-dose medroxyprogesterone acetate versus tamoxifen. A randomized crossover trial in postmenopausal patients with advanced breast cancer

In a prospective randomized multicenter study in previously untreated postmenopausal patients with advanced breast cancer, the response to treatment with oral medroxyprogesterone acetate (MPA) 300 mg three times daily was compared with tamoxifen (TAM) 20 mg twice daily. Of 61 patients treated with MPA, 27 (44%) had a partial or complete remission, 6 showed no change, and 28 had progressive disease. Of 68 patients treated with TAM, 24 (35%) showed a remission, 15 no change, and 29 progression. The difference in response rate is not significant. However, 11 of 25 patients with osseous metastases as predominant site, responded to MPA and 7 of 31 to TAM (P = 0.05). Moreover, in patients older than age 70 years, 13 of 26 responded to MPA and 6 of 31 to TAM (P less than 0.05). Median duration of remission of all patients in the MPA arm was 17 months and in the TAM arm, 23 months (not significant). Median survival was 20 months for MPA and 26 months for TAM (not significant). After cross-over from TAM to MPA 8 of 31 patients responded and after cross-over from MPA to TAM, no response was seen in 27 patients. These data indicate that the response rate and duration to MPA and TAM are comparable, except in patients with osseous metastases and in patients older than age 70 years. MPA has more side effects, but seems to be more effective after cross-over, and may thus be reserved for second-line treatment.     

Interrelationship between Estradiol and Tamoxifen Responses for Clinical Breast Carcinoma Cells Cultured on Contact-sensitive Plates

An in vitro assay system for predicting the estradiol (E₂) sensitivity of clinical cancer cells was applied to 54 patients with breast carcinoma to compare the responses to E₂ and tamoxifen (TAM) with the estrogen receptor (ER) status. We found that 18 of the 35 cases in the ER-positive group and 6 of the 19 cases in the ER-negative group were stimulated by E₂. It is suggested that ER status alone can not predict the response of cultured cells to E₂ in clinical breast cancer. Cell growth of 11/35 (31%) of the ER-positive cases and that of 8/19 (42%) of the ER-negative cases was inhibited by E₂. Since the cases inhibited by E₂ could not be distinguished by ER status alone, an assay system based on a quantitative proliferative response was considered necessary. There were 20 (83%) cases of inhibition by TAM among the 24 stimulated by E₂. Only 18/35 (51%) of the ER-positive group exhibited growth inhibition by TAM. In our (CSP) assay, 20 (83%) of the 24 cases stimulated by E₂ were inhibited by TAM, 10 (91%) of the 11 E₂-insensitive cases were insensitive to TAM and 13 (68%) of the 19 cases inhibited by E₂ were stimulated by TAM. In short, TAM response and E₂ response tended to be inversely related (43/54=80%, P <0.01). Furthermore, the E₂-response rate showed a good correlation with the TAM-response rate (R₂= 0.825). These results indicate the feasibility of predicting individual tumor responses to either E₂ or TAM by using CSPs.     

Combined endocrine treatment of elderly postmenopausal patients with metastatic breast cancer; A randomized trial of tamoxifen vs. tamoxifen + aminoglutethimide and hydrocortisone and tamoxifen + fluoxymesterone in women above 65 years of age

The efficacy of combined endocrine therapy with tamoxifen (TAM), aminoglutethimide (AG), and hydrocortisone (H) or tamoxifen and fluoxymesterone (FLU) was evaluated against treatment with tamoxifen alone in 311 patients above 65 years of age with a first recurrence of a metastatic breast cancer. A total of 279 patients were eligible. The response rates were assessed for 258 fully evaluable patients and were the following for the TAM (N=94), the TAM+AG+H (N=83), and the TAM+FLU (N=81) groups, respectively, PR: 14, 18, and 21%, and CR: 20, 11, and 23%. The overall response rates are not statistically different (p=0.30). The 95% CL of difference in response rates for TAM vs. TAM+AG+H are –9–19% and for TAM vs. TAM+FLU –4–25%. Time to treatment failure was comparable with median values of 9.2, 7.7, and 9.2 months in the TAM, TAM+AG+H, and TAM+FLU group, respectively (p=0.17). The corresponding figures for survival are median times of 22.0, 24.1, and 21.1 months with a p-value of 0.62. Toxicity was more pronounced in both the combined treatment groups, and could in most instances be attributed to treatment with either AG+H or FLU. Currently, new specific aromatase inhibitors with lesser toxicity than AG are being evaluated in combination with TAM for treatment of primary and metastatic breast cancer. In conclusion, the simultaneous use of TAM and AG+H or FLU does not seem to improve the therapeutic efficacy in elderly postmenopausal patients with metastatic disease. So far, combined endocrine therapy in this group of patients should only be used in the context of clinical trials.     

Readministration of tamoxifen after adjuvant therapy for recurrent breast cancer

BACKGROUND: Previous series concerning tamoxifen (TAM) rechallenge did not obtain satisfactory results. Using stricter criteria, we now assess the usefulness of readministration of TAM as an initial therapy for patients with recurrent breast cancer. METHOD: The eligibility criteria were postmenopausal, estrogen receptor (ER) positive or unknown, at least 12 months of adjuvant TAM, a 6-month or longer drug-free period and no previous therapy after recurrence. A total of 10 patients were enrolled. TAM was administered in daily doses of 20 or 30 mg. RESULTS: The mean age of the patients at the time of recurrence was 64.8 years. The receptor status was positive in 8 patients and unknown in 2. The median disease-free interval (DFI) after mastectomy was 71.7 months. A complete response was observed in one patient, a partial response in 6, stable disease in 2, and progression in one. The response rate was thus 70%, with an additional two patients showing no progression over 6 months. Although only one patient with a DFI of less than 48 months showed a positive response, all patients with a DFI longer than 48 months showed a clinical response. The duration of response was less than 12 months in 3 patients and longer in 4. CONCLUSION: The post-adjuvant readministration of tamoxifen is a useful first choice therapy for postmenopausal recurrent breast cancer patients with positive ER and longer DFI.     

他莫西芬与子宫内膜癌——关于他莫西芬治疗的乳腺癌患者发生子宫内膜癌的回顾性研究

研究他莫西芬（Ｔａｍｏｘｉｆｅｎ，ＴＡＭ）治疗乳腺癌而发生子宫内膜癌的危险性及其病理特征。根据统计中心提供资料，查阅病历确认日本国立癌中心中央病院自１９６２年５月开院至１９９５年１２月间收治的２５例发生于乳腺癌后的子宫内膜癌病例。２５例中１３例因乳腺癌接受过ＴＡＭ治疗。１９９０年前２５年间仅发生９例，占同期收治子宫内膜癌总数的２．１％，而１９９０年后的５年中发生１６例，占同期收治的子宫内膜癌总数的７％，其中１３例接受过ＴＡＭ治疗。ＴＡＭ组中组织学８４．６％属低度恶性（ｇｒａｄｅ１～２），与非ＴＡＭ组中８３．３％相近。闭经后或有恶性肿瘤家族史者易受ＴＡＭ作用发生子宫内膜癌。ＴＡＭ增加了子宫内膜癌的发病危险，ＴＡＭ组子宫内膜癌的病理类型及恶性度与非ＴＡＭ组相同     

Aminoglutethimide and aminoglutethimide+tamoxifen treatment for advanced breast cancer]

Twenty-eight and 24 patients with advanced breast cancer were treated with Aminoglutethimide (AG) or AG + Tamoxifen (AG + TAM) from June 1984 to June 1989, respectively. Evaluated cases were 25 and 21 treated with AG or AG+TAM, respectively. Objective response was seen in 5/25 (20.0%) for AG treatment with 9, 13, 16, 20 and 31 months remission and 4/21 (19.1%) for AG + TAM treatment with 6, 7, 12 and 26 months remission. Response rate according to dominant site of metastases were 1/10 in soft tissue, 2/7 in bone, 2/7 in lung and pleura treated with AG, 1/9 in soft tissue, and 3/5 in lung treated with AG + TAM treatment. Two of the 5 responding patients in AG treatment group had prior tamoxifen treatment and 3 out of 4 responding patients in AG + TAM treatment group had prior chemoendocrine therapy with tamoxifen and FAC chemotherapy. Main toxic side effects were lethargy and/or rash, and drug discontinuation was required in 3 cases of AG treatment group and 2 cases of AG + TAM treatment group. Serial determination of serum hormone levels during AG or AG + TAM treatment revealed a decrease in estrone and an increase in androstenedione in many cases of both treatment groups. This data suggested that AG treatment may be favorable for endocrine treatment for advanced breast cancer patients, but the response to AG was not augmented by adding TAM.     

Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16

The National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted a randomized clinical trial to determine whether tamoxifen (TAM) plus chemotherapy is more effective than TAM alone in improving disease-free survival (DFS), distant disease-free survival (DDFS), and survival (S) of positive-node, TAM-responsive patients aged greater than or equal to 50 years. Women were randomized among three treatment groups: (1) TAM alone, (2) Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and TAM (ACT), or (3) melphalan (L-PAM), fluorouracil (5-FU), and TAM (PFT). The PFT arm was later modified so that new patients also received Adriamycin (PAFT). Findings from 1,124 eligible patients through 3 years of follow-up indicated a significantly better DFS for ACT-treated patients than for those receiving TAM alone (84% v 67%; P = .0004). An advantage in DDFS and S was also observed after ACT therapy (83% v 73% [P = .04 in the former] and 93% v 85% [P = .04 in the latter]). Both the DFS and DDFS of PAFT-treated patients were better than in those treated by TAM alone (83% v 66%, P = .0002 and 85% v 73%, P = .003). PFT patients also fared better in DFS and DDFS than TAM patients (81% v 72%, P = .07 and 85% v 74%, P = .02). Odds ratios consistently favored the three TAM-plus-chemotherapy groups. No significant S advantage is as yet evident in favor of the PAFT or PFT groups. Of importance is the failure of these studies to demonstrate an unfavorable interaction between the drug regimens used and the TAM, which was administered simultaneously. The findings related to the use of PAFT and PFT are of more biologic than clinical significance since L-PAM is rarely used in the treatment of breast cancer. The major conclusion from this study is the observance of a better outcome in positive-node breast cancer patients aged greater than or equal to 50 years from the use of postoperative prolonged TAM and short-course AC therapy (completed in 63 days) than from prolonged TAM therapy alone.     

穿刺加三苯氧胺治疗乳腺囊肿的疗效观察(附36例)

目的：比较乳腺可扪及囊肿穿刺抽液后服用三苯氧胺和单纯穿刺抽液两种治疗方法的疗效.方法：将临床可扪及乳腺囊肿根据乳腺B超检查结果入组68例,随机分为穿刺抽液治疗组32例和穿刺抽液后服三苯氧胺治疗组36例,两组患者穿刺抽液后中位随访13个月观察疗效.结果：68例可扪及乳腺单纯囊肿,平均囊肿大小23mm,36例穿刺服三苯氧胺组复发率13.89%（5/36）,32例穿刺抽液组复发率37.50%（12/32）,两组相比较（P＜0.05）有显著性差异.乳腺囊肿病史＞1年的患者,穿刺服三苯氧胺组和穿刺组复发率分别是36.36%（4/11）和77.78%（7/9）,两组相比较（P＜0.05）差异有显著性.对单个囊肿,多发囊肿,囊肿病史＜1年患者,两种治疗方法不影响复发率（P＞0.05）.结论：临床可扪及乳腺单纯囊肿可根据B超检查筛选适合穿刺患者,穿刺抽液加服三苯氧胺治疗可减少复发,囊肿病史＞1年者复发率较高.     

Adjuvant tamoxifen for pre- and postmenopausal women with estrogen receptor positive,node positive breast cancer: A randomized study

Summary 370 patients with operable, axillary node positive breast cancer, were randomized to receive tamoxifen (TAM) 20 mg/day for 2 years or no adjuvant hormone therapy. All patients had estrogen receptor (ER) positive (ER > 10 pmol/g) primary tumours. 350 patients, 93 younger than 50 years of age and 257 patients 50 years or older, were evaluable for the study. After a median follow up of 76 months, significantly (p = 0.0001) fewer loco-regional, but not distant (systemic), relapses have been recorded in the TAM group. Overall survival was also improved, but even though the study was designed to give maximum benefit from TAM statistically significant effect of TAM seemed to be limited to patients 50 years of age and older.