Breast cancer risk with postmenopausal hormonal treatment

This review was designed to determine from the best evidence whether there is an association between postmenopausal hormonal treatment and breast cancer risk. Also, if there is an association, does it vary according to duration and cessation of use, type of regimen, type of hormonal product or route of administration; whether there is a differential effect on risk of lobular and ductal cancer; and whether hormone treatment is associated with breast cancers that have better prognostic factors? Data sources for the review included Medline, the Cochrane Database of Systematic Reviews (Cochrane Library, 2005) and reference lists in the identified citations. Eligible citations addressed invasive breast cancer risk among postmenopausal women and involved use of the estrogen products with or without progestin that are used as treatment for menopausal symptoms. Abstracted data were demographic groupings, categories of hormone use, categories of breast cancer, two-by-two tables of exposure and outcome and adjusted odds ratios, relative risks (RRs) or hazard rates. Average estimates of risk were weighted by the inverse variance method, or if heterogeneous, using a random effects model. The average risk of invasive breast cancer with estrogen use was 0.79 [95% confidence interval (95% CI) = 0.61-1.02] in four randomized trials involving 12 643 women. The average breast cancer risk with estrogen-progestin use was 1.24 (95% CI = 1.03-1.50) in four randomized trials involving 19 756 women. The average risks reported in recent epidemiological studies were higher: 1.18 (95% CI = 1.01-1.38) with current use of estrogen alone and 1.70 (95% CI = 1.36-2.17) with current use of estrogen-progestin. The association of breast cancer with current use was stronger than the association with ever use, which includes past use. For past use, the increased breast cancer risk diminished soon after discontinuing hormones and normalized within 5 years. Reasonably adequate data do not show that breast cancer risk varies significantly with different types of estrogen or progestin preparations, lower dosages or different routes of administration, although there is a small difference between sequential and continuous progestin regimens. Epidemiological studies indicate that estrogen-progestin use increases risk of lobular more than ductal breast cancer, but the number of studies and cases of lobular cancer remains limited. Among important prognostic factors, the stage and grade in breast cancers associated with hormone use [corrected] do not differ significantly from those in non-users, but breast cancers in estrogen-progestin users are significantly more likely to be estrogen receptor (ER) positive. In conclusion, valid evidence from randomized controlled trials (RCTs) indicates that breast cancer risk is increased with estrogen-progestin use more than with estrogen alone. Epidemiological evidence involving more than 1.5 million women agrees broadly with the trial findings. Although new studies are unlikely to alter the key findings about overall breast cancer risk, research is needed, however, to determine the role of progestin, evaluate the risk of lobular cancer and delineate effects of hormone use on receptor presence, prognosis and mortality in breast cancer.     

A clinical trial of adjunctive oestrogen treatment in women with schizophrenia

Summary A double-blind, 28-day, placebo-controlled study was conducted with three groups of women of child-bearing age (N = 12 in each group) who received standardised antipsychotic medication plus a) 50 μg transdermal estradiol or b) 100 μg transdermal estradiol or c) transdermal placebo. Preliminary analyses show that women receiving 100 μg of estradiol made greater improvements in the symptoms of schizophrenia than either the 50 μg estradiol or placebo groups. The addition of 100 μg adjunctive transdermal oestrogen significantly enhanced treatment responsivity of acute, severe psychotic symptoms in women with schizophrenia. The positive impact of oestrogen treatment on psychotic symptoms via a multiplicity of possible actions (see accompanying articles in this issue) may prove clinically useful in the overall treatment of women with schizophrenia. Accepted June 2002, Published online September 16, 2002 Correspondence: Prof. Jayashri Kulkarni, Alfred Psychiatry Research Centre, Alfred Hospital, Commercial Road, Prahran. Vic. 3181, Australia; e-mail: jayashri.kulkarni@med.monash.edu.au     

小鼠室旁核内雌激素受体与催产素、加压素表达的免疫组化研究

目的研究雌激素的核受体ER-α和ER-β以及催产素、加压素在成年雌性小鼠下丘脑室旁核内的表达。方法采用硫酸镍铵增强显色的免疫组化SP法检测ER-α、ER-β、催产素和加压素在室旁核内的表达。结果雌激素的两种核受体在室旁核内都有表达,但是以ER-β为主（P〈0.001）,其免疫阳性产物均在细胞核内,未见核外免疫阳性反应。催产素的免疫阳性产物主要在细胞核周围的胞浆即核周质内,而加压素的免疫阳性物质除了在核周质内有很强的反应外,在突起内也可见很强的免疫反应。ER-α的免疫阳性胞体主要在大细胞部内侧,而ER-β、催产素和加压素的免疫阳性胞体主要在背侧帽部或大细胞部的外侧。结论室旁核内两种雌激素受体可能都参与了对催产素和加压素的调节,但ER-β可能发挥了主要的调节作用。     

Histological grade in invasive ductal carcinoma of breast correlates with the proliferative activity evaluated by BrdU: An immunohistochemical study including correlations with p53, c-erbB-2 and estrogen receptor status

Thirty cases of invasive ductal carcinoma of the breast were classified to histological subtype according to the General Rules for Clinical and Pathological Recording of Breast Cancer of the Japanese Breast Cancer Society and histologically graded using the Nottingham method and the correlation of histology with proliferative activity was investigated using bromodeoxyuridine (BrdU). In addition, the overexpression of p53 protein, c-erbB-2 oncoprotein and estrogen receptor (ER) were immunohistochemically examined in order to discuss the relationship with histological subtype and histological grade. Histological grade correlated positively to the BrdU labeling index (LI) and overexpression of p53. High grade carcinoma demonstrated c-erbB-2 more frequently and exhibited a low incidence of ER. However, no significant relationship was found between BrdU LI, overexpression of p53 and c-erbB-2 and histological subtype. These results suggest that the histological grade does represent the proliferative activity of tumor cells and that adding the histological grade to the pathological diagnosis in invasive ductal breast carcinoma may be useful from the clinicopathological aspect concerning tumor behavior.     

Estrogen decreases expression of chemokine receptors, and suppresses chemokine bioactivity in murine monocytes

Problem:  We propose that the ability of estrogen exposure to increase the probability of a woman developing breast cancer may be related to decreased chemokine activity and suppression of immune surveillance in mammary tissue. The present study was conducted to determine whether estrogen could decrease monocyte bioactivity through alteration of chemokine receptor expression.
Method of study:  We examined the effect of estrogen and tamoxifen on the expression of the chemokine receptors CCR2 and CXCR3 on murine monocytes treated in culture and in vivo . Effects of estrogen on chemokine activation of monocytes were also evaluated.
Results:  Estrogen and tamoxifen significantly decreased expression of CCR2 and, to a lesser extent, CXCR3 on murine monocytes. Estrogen decreased chemotaxis of monocytes towards MCP-1/JE. The chemokines MCP-1/JE and MIP-1 α were unable to evoke increases in intracellular calcium in murine monocytes treated with estrogen, alone or in combination with tamoxifen.
Conclusions:  Our results show that estrogen suppresses the ability of monocytes to respond to certain chemokines, suggesting that estrogen exposure might decrease immune surveillance in tissues where the action of specific chemokines is involved.     

同型半胱氨酸经甲基化修饰下调去卵巢大鼠主动脉雌激素受体α基因的表达

目的观察同型半胱氨酸(Hcy)对大鼠雌激素受体α(ERα)基因表达和其启动子CpG岛甲基化的影响。方法高效液相色谱仪检测血浆Hcy水平;RT-PCR和甲基化特异性PCR(MSP)分别检测ERαmRNA表达水平及基因启动子CpG岛的甲基化状态。结果去卵巢和给予甲硫氨酸饮食均可升高大鼠血浆Hcy水平。去卵巢和Hcy均可使大鼠ERαmRNA表达减少,但5′-Aza可使细胞ERαmRNA表达增多。假手术组大鼠主动脉ERα基因启动子有2例(20%)存在甲基化,去卵巢组有3例(30%)存在甲基化,而去卵巢 Hcy组有6例(60%)存在甲基化,对照组细胞ERα启动子CpG岛完全去甲基化,Hcy组细胞甲基化增强,5′-Aza使细胞去甲基化。结论Hcy可经甲基化修饰方式下调去卵巢大鼠主动脉ERαmRNA表达。     

免疫电镜技术运用过程中电子染色方法的选用

目的探究免疫电镜不同染色方法对免疫组化阳性实验结果影响的关系。方法组织切片经常规免疫组化（雌激素受体GPR30）并行DAB-硫酸镍铵显色后进行电镜切片，然后分为双氧铀-柠檬酸铅双染、双氧铀单染与未染色3组，以便对不同电子染色结果进行比较。结果GPR30免疫阳性产物位于细胞核外的膜性结构上，在铀-铅双染组显示很高的电子密度，但是背景染色也很深，在铀单染组的反差比较好，而未染色组的反差更好。结论免疫电镜技术中针对不同的免疫阳性反应选用不同的电子染色方法，有利于阳性结果的判断与鉴别。     

乳腺癌ER,PR状态与细胞超微结构变化的形态定量分析

用免疫组化ＰＡＰ法检测３０例乳腺癌雌激素受体（ＥＲ）和孕激素受体（ＰＲ），从中选取ＥＲ、ＰＲ阳性者（Ｅ＾＋Ｐ＾＋）６例，阴性者（Ｅ＾－Ｐ＾－）５例作透射电镜观察，对部分细胞器连接的变化进行形态定量分析。结果Ｅ＾－Ｐ＾－组癌细胞内线粒体、粗面内质网及溶酶体的含量明显高于Ｅ＾＋Ｐ＾＋组，且差异有显著性（Ｐ＜０．０５，０．０１，０．０１）；Ｅ＾－Ｐ＾－组细胞间的桥粒及镶嵌连接有减少趋势，但差异无显著性     

Estrogen stimulates neuronal plasticity in the deafferented hypothalamic arcuate nucleus in aged female rats

The hypothalamic arcuate nucleus (ARCN) was examined ultrastructurally 3 weeks after the complete deafferentation of the medial basal hypothalamus (MBH) with the island isolation technique in ovariectomized aged female rats (720-930 days of age). The mean numbers of axodendritic and axosomatic synapses in the ARCN decreased to about one-third of those in the intact controls. However, the treatment with estradiol benzoate (2 micrograms/day) during the 3 weeks following the day of brain surgery brought about a marked increase in the numbers of these synapses. The data suggest that the ARCN neurons of aged female rats still retain plasticity to react to deafferentation under influences of estrogen.     

雌激素对卵巢摘除大鼠心内神经节细胞Bcl-2和Bax表达的影响

本实验建立了去卵巢和雌激素替代疗法动物模型,用免疫组织化学SABC法结合图象分析方法,观察大鼠心内神经节细胞中Bcl-2和Bax的变化,探讨雌激素对卵巢摘除大鼠心内神经节细胞中Bcl-2和Bax表达的影响。去卵巢(OVX)大鼠心内神经节细胞中Bcl-2的表达较正常对照组明显减弱(P<0.05),雌激素替代治疗组大鼠心内神经节中Bcl-2的表达与正常对照组相比无显著性差异(P>0.05),而较卵巢摘除组显著增高(P<0.05);卵巢摘除后同时给予特异性雌激素受体阻断剂(TAM)和17β-雌二醇(OVX+TAM+ERT)组大鼠心内神经节中Bcl-2的表达较正常对照组显著减弱(P<0.05),但与OVX组无显著性差异(P>.05)。各组中Bax的表达无显著性差异(P>0.05)。实验结果提示雌激素能上调大鼠心内神经节细胞中Bcl-2的表达,但对Bax的表达无影响。