Tamoxifen effects on subjective and psychosexual well-being,in a randomised breast cancer study comparing high-dose and standard-dose chemotherapy

To evaluate the impact of tamoxifen on subjective and psychosexual well-being in breast cancer patients in relation to type of prior chemotherapy and menopausal status. Longitudinal interview study in breast cancer patients during and after adjuvant tamoxifen use. Menopausal status was defined by last menstrual period and serum oestradiol and FSH levels. Gynaecology outpatient clinic, Tertiary Referral Hospital, January 1995 to September 1999. Breast cancer patients <56 years of age, participating in a randomised trial comparing adjuvant high-dose (n=45) and standard-dose (n=53) chemotherapy, followed by radiotherapy and tamoxifen. Relative incidence and correlation of subjective and psychosexual symptoms during and after tamoxifen. During tamoxifen the most frequent complaints were hot flushes (85%), disturbed sleep (55%), vaginal dryness and/or dyspareunia (47%), decreased sexual desire (44%) and musculo-skeletal symptoms (43%). Disturbed sleep correlated with hot flushes (P<0.0005) and concentration problems (P<0.05). Decreased sexual interest correlated with vaginal dryness (P<0.0005) and/or dyspareunia (P<0.0005). In the high-dose group more patients became postmenopausal (95% vs 33%) and more patients reported symptoms than in the standard-dose group (P<0.05). After discontinuation of tamoxifen, symptoms decreased significantly. However, hot flushes, disturbed sleep and vaginal dryness persisted more often in patients who remained postmenopausal after high-dose chemotherapy (P<0.05). Overall, during tamoxifen patients reported many symptoms. More patients become postmenopausal after high-dose chemotherapy, and they remain often symptomatic after tamoxifen.     

氯离子通道阻断剂对大鼠低氧性肺动脉高压的影响

目的:探讨氯离子通道阻断剂三苯氧胺(tamoxifen,TAM)对大鼠低氧性肺动脉高压的治疗效果。方法:雄性Wistar大鼠96只,随机分为:(1)治疗组(缺氧+三苯氧胺,H/Q):大鼠在常压缺氧(10%,每日8 h)箱内饲养,缺氧前3 d开始灌胃三苯氧胺0.4 mg.kg-1.d-1,每日1次;(2)缺氧组(H组):每日给予相等量的生理盐水,余同治疗组;(3)正常对照组(C组)。测定各组大鼠d 4、7、14、21右心室/(左心室+室间隔)厚度,多导生理记录仪记录肺动脉平均压(mPAP),图像分析仪测定血管管壁面积占管总面积的百分比(WA/TA)和血管管腔面积占管总面积的百分比(VA/TA)。结果:缺氧组d 7mPAP开始升高,d 21达高峰,治疗组同时间点明显低于缺氧组;缺氧组RV/(LV+S)d 14开始上升,d 21达高峰,治疗组同时间点明显低于缺氧组;缺氧组d 21的血管管壁面积占管总面积的百分比(WA/TA)显著高于d 21治疗组(P<0.05)。而缺氧组d 21的血管管腔面积占管总面积的百分比(VA/TA)显著低于d 21治疗组(P<0.05)。结论:氯离子通道阻断剂三苯氧胺可降低缺氧所致大鼠肺动脉压升高、改善右心室肥厚及肺小动脉增厚,对低氧性肺动脉高压有一定的治疗作用。     

单用TAM及联合应用5-FU对结肠癌细胞株生长抑制作用及增殖凋亡的影响

目的探讨他莫昔芬(tamoxifen,TAM)单独或联合5-FU化疗对结肠癌细胞株生长抑制作用及凋亡的影响.方法应用MTT法,比较单纯应用TAM和TAM与5-FU联合对SW480、HT29细胞株生长抑制作用,通过药物量-效关系曲线,观察TAM有无化疗增敏作用,同时检测PCNA和AI,探讨TAM联合5-FU对增殖、凋亡的影响.结果单独应用TAM对SW480、HT29细胞株无生长抑制作用;TAM联合5-FU在一定浓度时可抑制SW480和HT29细胞的生长,提高对5-FU的敏感性,起到化疗增敏作用.通过对PCNA和AI 2个指标的检测,随着浓度的增加和时间的延长,TAM联合5-FU抑制细胞的增殖和促进细胞的凋亡均呈上升趋势.结论一定浓度的TAM能增加人结肠癌细胞株SW480、HT29对化疗药物5-FU的敏感性,抑制细胞增殖,促进细胞凋亡.     

The Diagnosis and Treatment of Ductal Carcinoma In Situ of the Breast

Abstract: Ductal carcinoma in situ of the breast is the most favorable presentation of breast cancer; therefore appropriate local treatment is imperative. Intraductal carcinoma is being diagnosed more frequently with the increasing use of screening mammography. A number of pathologic features have been identified which are useful for classification and for prognostic information. In addition, the molecular pathology and its relationship to tumor behavior and prognosis is becoming more well understood. The role of axillary dissection has been examined in a number of series and is generally agreed to be unnecessary for this presentation of breast cancer, allowing many women to avoid the sequela of axillary surgery. This review discusses the use of breast conservation treatment and the evolving indications for excision alone in the treatment of ductal carcinoma in situ. The outcomes for breast conservation therapy from both randomized trials and institutional series have confirmed excellent survival rates. Salvage therapy for local recurrence is frequently successful, resulting in nearly equivalent survivals in women undergoing breast conservation therapy compared to mastectomy. In addition, intriguing but preliminary results from both breast cancer prevention studies and trials looking at the use of tamoxifen for intraductal cancer suggest a local control benefit in women using the drug.     

小剂量米非司酮联合三苯氧胺配伍米索前列醇终止早孕的临床研究

目的 :观察 75 mg米非司酮联合三苯氧胺用于药物流产的效果。方法 :2 0 5例早孕≤ 49d的妇女双盲随机分为两组 ,研究组 :d1早、晚各服 2片和 1片米非司酮 ,分别加服 2片三苯氧胺 ,d2早、晚分别口服 2片三苯氧胺 ,d3阴道放置米索 6 0 0 μg。对照组 :d1早、晚各服 2片和 1片米非司酮 ,分别加服 2片安慰剂 ,d2早、晚分别口服 2片和 1片米非司酮 ,晚加服 1片安慰剂 ,d3阴道放置米索 6 0 0μg。结果 :两组完全流产率无明显差异 (P>0 .0 5 ) ,而研究组完全流产后阴道出血持续天数缩短 (P<0 .0 0 1 )。结论 :小剂量米非司酮配伍三苯氧胺可有效终止早孕并减少流产后出血。     

生长抑素增强三苯氧胺抗乳腺癌作用的体外研究

Objective:To study the antineoplastic effects of tamoxifen(TAM) in combination with a somatostain analogue(octreotide,OCT) on breast cancer.Methods:Estrogen receptor(ER)-positive(MCF-7) and ER-negative(MDA-MB-435S)human breast carcinoma cell lines were treated with TAM or OCT,or combination of both agents in vitro.Cell proliferation was evaluated by MTT assay,distribu-tion of cell cycle and rate of apoptosis were detemined by flow cytometry.Results:The inhibitory effect of OCT or TAM on proliferation of MCF-7 cells was associated with cell arrest in G0/G1 phase and induction of apoptosis.The inhibitory effect on proliferation of MCF-7 cells enhanced when treatment of TAM combined with OCT.The increased rate of apoptosis induced by combination of TAM and OCT was much higher than use of either TAM or OCT alone.TAM or OCT also had weak inhibitory effect on MDA-MB435S cell.The cells were arrested at S phase by TAM and at G0/G1 phase by OCT, but the induction of apoptosis was not identified.However,the rate of apoptosis was 22.7% if combined treatment of TAM and OCT applied.Conclusion:TAM and OCT can synergistically inhibit proliferation and induce apoptosis of ER-positive and ER-negative breast cancer cells.The synergism of TAM and OCT may be of interest in the clinical treatment of breast carcinoma.     

Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: a randomized study.

BACKGROUND: Hot flashes are frequent in postmenopausal breast cancer patients, especially when treated with tamoxifen. Estrogen replacement therapy is the most effective treatment for hot flashes, but its use is controversial in breast cancer survivors. Progestins may offer a good alternative for the control of hot flashes in this setting; in particular, oral megestrol acetate has been proven effective in a randomized, placebo-controlled clinical trial. With the aim of further improving these results, we have designed a randomized study comparing oral megestrol acetate with depot intramuscular (i.m.) medroxyprogesterone acetate (MPA) for the control of hot flashes in postmenopausal patients with a history of breast cancer. PATIENTS AND METHODS: Seventy-one postmenopausal patients were randomized to receive an i.m. injection of depot MPA 500 mg on days 1, 14 and 28, or oral megestrol acetate 40 mg daily for 6 weeks. Patients recorded daily the number and severity of their hot flashes; response was defined as a > or =50% decrease in the number and severity of hot flashes. RESULTS: At week 6, hot flashes were reduced by 86% on average in the whole group of patients, without significant differences between the two progestins. Response was obtained by 75 and 67% of patients receiving MPA or megestrol, respectively (P = 0.5). Responders were followed to assess maintenance of response (without further treatment), which was significantly better with i.m. MPA: in this group, 89% of responders still showed a benefit at week 24, compared with 45% in the megestrol group (P = 0.03). CONCLUSIONS: Our study shows that a short cycle of i.m. depot MPA injections provides significant and long-lasting relief from postmenopausal hot flashes in patients with a history of breast cancer, offering an alternative to estrogen replacement therapy or prolonged administration of oral megestrol.     

Ovarian hemangioma associated with tamoxifen therapy: a case report

Vascular tumors of the ovary are very rare. We report a case of ovarian hemangioma in a patient treated with tamoxifen for breast ductal carcinoma. CD31 and CD34 immunoreactivity confirmed the vascular origin of the tumor. It is interesting to note that estrogen and progesterone receptors were negative in endothelial cells of the hemangioma, but were positive in stromal ovarian cells. Tamoxifen is a synthetic, non-steroidal, anti-estrogenic drug widely used as adjuvant therapy for pre- and post-menopausal, early and metastatic, breast cancer patients with positive estrogen receptor proteins. The mechanism of action of tamoxifen in stimulating the development and/or growth of ovarian hemangioma is unknown. We may speculate that its prolonged, estrogenic effect on the ovary may be one of the stimulating factor.     

成神经细胞瘤雌激素受体与临床关系探讨

目的了解成神经细胞瘤雌激素受体（ＥＲ），探索新疗法。方法运用酶联亲和组织化学法检测成神经细胞瘤２９例，选择３例ＥＲ阳性的Ⅳ期患儿，加用三苯氧胺治疗。结果ＥＲ阳性率５１７％（１５／２９）。其中＜１岁组阳性率为２／３（例），１～３岁为２／８（例），４～６岁为３／１０（例），７～１０岁为８／８（例）。病理预后较好类型者ＥＲ阳性率为１６７％（１／６），而预后差类型者为６８４％（１３／１９），显著高于前者（Ｐ＜００５）。３例患儿服用三苯氧胺后疼痛症状暂时缓解或存活期延长。结论成神经细胞瘤ＥＲ阳性率较高，ＥＲ可作为成神经细胞瘤预后的指标。三苯氧胺是潜在的治疗药物。     

Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels

A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p=0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p=0.53 and p=0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment.In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.