绝经前乳腺癌组织雌激素受体与血清雌激素水平相关性的初步探讨

目的:探讨绝经前乳腺癌雌激素受体(ER)表达与患者血清雌激素(E2)水平的关系。方法:使用全自动免疫分析仪化学发光分析法检测84例乳腺癌患者血清性激素6项(LH、FSH、PRL、E2、P和T)水平,免疫组化EnVi-sion二步法检测乳腺癌ER表达状态。据ER检测的结果,分为阳性及阴性两组,对其对应的雌激素数值进行统计学分析。结果:在P临界值设定为0.05水平下,进行t检验,t=-1.59912,P=0.11364,两组样本中显现的E2水平差异无统计学意义。结论:绝经期前乳腺癌患者ER表达可能与雌激素水平无关。     

血清睾酮水平与乳腺癌雌、孕激素受体表达的相关性研究

目的:回顾性研究血清睾酮（testosterone,T）水平与乳腺癌雌激素受体（estrogen receptor,ER）,孕激素受体（progesterone receptor,PR）表达的相关性。方法:回顾性分析2016年1月至2018年12月在南京市妇幼保健院进行体检和治疗的63例健康女性,99例良性肿瘤,204例乳腺癌的临床病理资料,比较三组之间的血清睾酮水平的差异。将所有204例乳腺癌患者根据睾酮水平由低到高排序,按四分位数分为4组,采用Logistic回归比较不同睾酮水平下4组乳腺癌患者ER、PR、Her2表达状态的比值比（OR）。结果:乳腺癌组血清睾酮水平与乳腺良性肿瘤组、健康对照组相比差异均无统计学意义（P＞0.05）。ER+和PR+乳腺癌患者中血清睾酮水平分别高于ER-和PR-患者,而Her2+乳腺癌患者中血清睾酮水平低于Her2-患者,差异均有统计学意义（P＜0.05）。采用Logistic回归计算OR值,根据绝经与否进一步分层,其中T≥0.44 ng/mL组相对于T≤0.22 ng/mL组ER阳性表达的总体OR值为2.46（95%CI=1.04~5.86,P=0.042）,绝经前OR值为3.77（95%CI=1.11~12.80,P=0.034）,绝经后OR值为1.05（95%CI=0.28~3.92,P=0.945）;T≥0.44 ng/mL组相对于T≤0.22 ng/mL组PR阳性表达的总体OR值为3.69（95%CI=1.60~8.49,P=0.002）,绝经前OR值为4.80（95%CI=1.51~15.23,P=0.008）,绝经后OR值为1.78（95%CI=0.47~6.71,P=0.396）,结果显示绝经前乳腺癌患者中ER、PR的阳性表达与血清睾酮水平呈现出明显的正相关性;而Her2阳性表达与血清睾酮水平在总体、绝经前、绝经后乳腺癌患者中均未表现出明显的负相关性。结论:高血清睾酮水平与乳腺癌ER、PR的阳性表达呈正相关,在绝经前乳腺癌患者中表现尤为显著。血清睾酮水平可以作为预测绝经前激素受体状态的标志物之一。     

乳腺增生与乳腺癌组织中雌激素受体、孕激素受体的表达差异及其临床意义

 目的　探讨乳腺增生及乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）的表达差异及其临床意义。方法　采用免疫组织化学方法检测68例乳腺增生和168例乳腺癌标本中ER、PR的表达。结果　 乳腺癌患者ER表达水平明显高于乳腺增生患者（P＜0.05）,而PR在两组中的表达差异无统计学意义。绝经后乳腺癌患者ER表达水平中位值为30 %,明显高于绝经后乳腺增生患者的10 %（P＜0.05）,而在绝经前两组患者ER表达水平差异无统计学意义。浸润性小叶癌组织内PR的表达明显高于浸润性导管癌等其他类型,差异有统计学意义（P＝0.005）。结论　ER、PR的表达能够较好地反映乳腺疾病的病理生物学特征。     

乳腺癌绝经前后c-erbB-2、ER、PR的表达及与预后的相关性

 目的 探讨乳腺癌绝经前后c-erbB-2、ER、PR受体的表达差异及其与预后的相关性。 方法 回顾性分析432例乳腺癌的病理学资料,其中195例患者随访5年,c-erbB-2、ER、PR的表达采用免疫组化法检测。 结果 （1）绝经前组,c-erbB-2阳性患者的ER阳性率显著低于c-erbB-2阴性患者（P=0.003）;绝经后组,c-erbB-2阳性患者的ER、PR阳性率均显著低于c-erbB-2阴性患者（P＜0.001,P=0.005）。（2）多因素分析显示,绝经前组的独立预后因素为淋巴结转移、c-erbB-2,绝经后组的独立预后因素为淋巴结转移、c-erbB-2和ER。 结论 绝经前与绝经后乳腺癌c-erbB-2、ER、PR受体表达的临床意义有所不同。     

绝经前乳腺疾病患者性腺轴系激素水平量化分析及其临床意义

目的:研究绝经前(滤泡期或称卵泡前期)的女性乳腺增生和乳腺癌患者HPO轴系激素表达,包括激素雌二醇(E2)、促卵泡激素(FSH)、促黄体激素(LH)、孕酮(P)、睾酮(T)和促催乳素(PRL)6种,为乳腺增生和乳腺癌提供诊断依据。方法:采用放射免疫法检测正常人、乳腺增生和乳腺癌患者各62例血浆E2、FSH、P、T和PRL水平(E2、P和T单位为μg/L,FSH和LH单位为I U/L,PRL单位为g/L),并应用逻辑回归与判别分析等方法进行统计分析。结果:乳腺癌、乳腺增生症和正常人3组人群的激素分布不同,乳腺癌患者的E2(192.59)、FSH水平增高(24.25),LH(30.235 3)与E2、FSH存在协同性增高,Logistic回归分析和聚类分析发现,T水平乳腺癌组低于乳腺增生与正常人群组,差异有统计学意义,P<0.05。P和PRL水平越高,患乳腺癌的危险度上升。结论:通过回归分析和聚类分析,可能提高临床应用性激素检测判别疾病的能力及危险度预测,判别准确率为91.2%。     

青年乳腺癌雌激素受体与Ki-67关系的研究

目的 研究青年乳腺癌雌激素受体表达与Ki-67指数的关系.方法 采用免疫组化S-P法,用抗ER、Ki-67单克隆抗体,研究32例青年乳腺癌和36例绝经后乳腺癌ER与Ki-67的表达.结果 青年乳腺癌17例(53.13%)ER阳性,绝经后乳腺癌20例(55.56%)ER阳性;青年乳腺癌ER阳性组Ki-67指数明显高于绝经后乳腺癌阳性组,差异有统计学意义(P＜0.01);而两者ER阴性组差异无统计学意义(P＞0.05).结论 青年乳腺癌ER阳性组肿瘤细胞增殖活性明显高于绝经后乳腺癌ER阳性组,这是青年乳腺癌恶性度高的重要原因.     

新辅助化疗对局部晚期乳腺癌组织中雌激素受体孕激素受体和人表皮生长因子受体2表达的影响

目的探讨新辅助化疗对晚期乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER-2)表达的影响。方法收集ⅡB^ⅢB期的局部晚期乳腺癌患者48例,应用免疫组化方法检测ER、PR和HER-2的表达后,给予表阿霉素(EPI)加多西紫杉醇(DOX)方案进行新辅助化疗,3个疗程后行根治手术,将术后标本中ER、PR和HER-2的表达与化疗前表达情况进行对照,分析新辅助化疗对免疫表达的影响。结果新辅助化疗前ER阳性表达率为33.3%,化疗后ER阳性表达率为52.1%;化疗前PR阳性表达率为35.4%,化疗后PR阳性表达率为50.0%。ER和PR阴性表达的患者在新辅助化疗后转为阳性表达的比例高于化疗前阳性转为阴性的比例,但差异没有统计学意义(P>0.05)。新辅助化疗前HER-2阳性表达率为62.5%,化疗后HER-2阳性表达率为52.1%,新辅助化疗后阳性转阴率略高于阴性转阳率,差异无统计学意义(P>0.05)。结论新辅助化疗能使部分乳腺癌组织中ER、PR和HER-2的表达发生改变,为乳腺癌的治疗提供了一定的依据。     

乳腺癌超声征象与雌激素受体、孕激素受体及C-erbB-2表达的相关性分析

目的 探讨乳腺癌超声征象与雌激素受体(ER)、孕激素受体(PR)及C-erbB-2表达的相关性.方法 选取的82例乳腺癌患者均接受超声检查,观察肿瘤大小、分级、类型、淋巴结转移及脉管侵犯情况等;免疫组化法检测乳腺癌患者乳腺癌组织中ER、PR及C-erbB-2的阳性表达率,并分析不同超声征象与ER、PR及C-erbB-2阳性表达的相关性.结果 82例乳腺癌患者乳腺癌组织中ER、PR及C-erbB-2的阳性表达率分别为60.98％、58.54％和48.78％.不同边缘情况、恶性晕环情况、淋巴结转移情况和后方回声衰减情况乳腺癌患者乳腺癌组织中ER阳性表达率比较,差异均有统计学意义(P﹤0.05).不同边缘情况、淋巴结转移情况乳腺癌患者乳腺癌组织中PR阳性表达率比较,差异均有统计学意义(P﹤0.05).不同微钙化情况、血流情况、淋巴结转移情况乳腺癌患者乳腺癌组织中C-erbB-2阳性表达率比较,差异均有统计学意义(P﹤0.05).肿瘤边缘毛刺征与ER、PR的阳性表达均呈正相关(P﹤0.05),恶性晕环、后方回声衰减与ER的阳性表达均呈正相关(P﹤0.05),肿瘤微钙化、血流丰富与C-erbB-2的阳性表达均呈正相关(P﹤0.05),腋窝淋巴结转移与ER、PR的阳性表达呈负相关(P﹤0.05),与C-erbB-2的阳性表达呈正相关(P﹤0.05).结论 乳腺癌患者超声征象与ER、PR及C-erbB-2阳性表达存在一定的相关性,在预测乳腺癌生物学特性中具有一定指导价值.     

男性乳腺发育和乳腺癌与血清E2和ER及PR关系的临床研究

目的:研究男性乳腺发育、乳腺癌与雌激素水平、雌激素受体(ER)及孕激素受体(PR)之间的关系,探讨男性乳腺发育、乳腺癌患者病因及其临床治疗。方法:用放射免疫检测法测定了35例男性乳腺发育和20例正常献血员血清雌二醇(E2)、睾酮(T);用免疫组织化学SP法测定了35例男性乳腺发育、8例乳腺癌患者乳腺切除标本的ER和PR。结果:男性乳腺发育患者血清E2明显高于正常对照组(P=0·023),而T值两组差异无统计学意义;男性乳腺发育(77·1%、71·4%)、乳腺癌患者(87·5%、75·0%)病理标本ER、PR阳性率均较高。结论:男性乳腺发育、乳腺癌与体内E2水平及乳腺ER、PR相关,可能是机体环境中较高的雌激素及其相关激素一起与局部乳腺ER、PR相互作用,诱发男性乳腺发育,进而可能发展为乳腺癌;ER阻滞剂及降低雌激素水平的芳香化酶抑制剂可用于临床治疗男性乳腺发育和乳腺癌。     

雌激素孕激素受体阳性与雌激素受体阳性孕激素受体阴性乳腺癌的临床研究

目的探讨雌激素孕激素受体阳性与雌激素受体(ER)阳性孕激素受体(PR)阴性乳腺癌的临床病理特征及预后因素分析。方法收集2012年1月至2015年12月山东省肿瘤医院收治的398例女性乳腺癌患者的临床资料,分析病理学特征。应用χ2检验比较不同组的差异;应用COX回归模型分析疾病进展相关因素。结果低ER水平(HR 5.59,95%CI:2.42~12.95,P0.001)、低PR水平(HR 0.19,95%CI:0.04~0.90,P0.05)和高Ki-67增殖指数(HR 5.84,95%CI:1.91~17.85,P0.05)的患者复发率更高。ER+/PR+患者与ER+/PR-患者在肿瘤体积(P0.001)、病理分期(P0.001)、Ki-67水平(≥20%)(P0.001)、Her-2阳性表达(P0.05)等方面比较,差异有统计学意义。结论 ER+/PR-乳腺肿瘤比ER+/PR+乳腺肿瘤具有更强的侵袭性。     

Relation of serum levels of estrogen and dehydroepiandrosterone sulfate to hormone receptor status among postmenopausal women with breast cancer

Background: It is hypothesized that breast cancer may consist of heterogeneous diseases with different hormonal environments classified by hormone receptor status. Epidemiologic studies evaluating risk factors for breast cancer by hormone receptor status have supported the hypothesis. However, there are inconsistencies in the risk factor profiles by estrogen receptor (ER) and progesterone receptor (PR) across the studies. To clarify the heterogeneity of the disease, it is necessary to understand not only risk factor profiles but also the biologic characteristics such as the relationships among endogenous sex hormone levels and hormone receptors. Methods: We measured serum levels of estrone (E1), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) in 142 postmenopausal women aged 50 and over with primary breast cancer who had undergone surgical treatment, and investigated the heterogeneity in the relations of endogenous sex hormone levels to hormone receptor status, using the case-series study method. Subjects were categorized into 3 classes based on tertiles of each hormone level in receptor-negative subjects, and odds ratios (ORs) for receptor-positive status compared with receptor-negative status were computed, taking the lowest category as a reference category. Results: There were clear trends toward higher serum levels of E1, E2, and DHEAS in women with PR+ cancer. The case-series approach revealed that PR+ status might be strongly associated with serum sex hormone levels. In particular, the OR of PR+ was large for a high DHEAS level (OR for the highest category = 4.28). No significant association between serum hormone levels and ER status was observed. Conclusion: The association of serum sex hormone levels with hormone receptor status may differ by PR status, but not by ER status. This finding suggests that PR status may be related to the heterogeneity in hormonal environments associated with breast cancer risk.     

大剂量甲地孕酮治疗晚期乳腺癌的内分泌激素改变

目的：了解大剂量甲地孕酮治疗晚期乳腺癌后体内内分泌激素水平改变可能存在的临床意义。方法：选择女性晚期乳腺癌病例共24例以大剂量甲地孕酮（HDMA）治疗（1200mg/d);并测定治疗前后尿17－羟类固醇和17－酮类固醇和血清LH、FSH、E2、PRL、TSH和孕酮（P）水平。结果：LH和FSH降低有显统计意义;E2升高一倍,但没有统计学意义,而PRL升高则有显统计学意义;孕酮轻微下降和TSH轻微升高,无统计意义;24小时尿17－羟类固醇和17－酮类固醇排出量显增加。结论：HDMA可能是通过下丘脑－垂体－肾上腺（性腺）轴的负反馈抑制作用,使LH和FSH分泌下降;体内E2和PRL升高尽管未见与HDMA的临床疗效有确切相关性,但其高泌乳素和高雌激素水平可能对患的预后不利。     

Hormonal profiles and estrogen receptors in Egyptian female breast cancer patients

AIMS AND BACKGROUND: Hormones are considered to be an important factor in the etiology of breast cancer. Serum hormonal profiles of premenopausal and postmenopausal breast cancer patients as well as estrogen receptor (ER) concentrations in breast cancer tissues were examined in an attempt to establish a possible association between hormones and breast cancer risk and to elucidate the biological features of the disease among Egyptian female patients. METHODS: Levels of estradiol (E2), testosterone (T), progesterone (P), LH, FSH, prolactin, T3, T4 and TSH were measured by highly specific radioimmunoassays in the sera of women with breast cancer and compared to those of control subjects. ER concentrations in breast tumor tissues were measured using 125I-radioreceptor assay. RESULTS: Levels of T and prolactin showed a significant increase in both premenopausal and postmenopausal patients. E2 and P levels were significantly increased in follicular premenopausal and postmenopausal patients. Luteal E2 showed non-significant changes, whereas the luteal P level was significantly decreased. No significant alterations were found in the levels of serum LH, FSH, T3, T4 and TSH either in premenopausal or postmenopausal patients. Higher levels of ER were found in the tumors of postmenopausal than in those of premenopausal patients. A positive correlation was found between levels of ER and age of the patients (r = 0.35), whereas a negative correlation was observed between ER and serum E2 (r = -0.26). CONCLUSIONS: This study provides evidence of an association between high levels of serum E2 and T and increased risk of breast cancer in postmenopausal women. Abnormalities in serum P and prolactin are probably associated with a breast cancer risk and ER may be considered as a biochemical marker for breast cancer development.     

Female sex steroid receptor status in primary and metastatic breast carcinoma and its relationship to serum steroid peptide hormone levels

In order to obtain more information on the interrelationships between cytosol estrogen (ER) and progestin (PR) receptors in breast carcinoma, and their distribution according to age, menopausal status and endocrine parameters of the patients, these receptors were measured in 605 primary and 150 metastatic lesions, and correlated with serum levels of estradiol, progesterone, FSH, LH and prolactin in some of these patients. Measurable estrogen receptor (> 3 fmol/mg cytosol protein) was found in 78.0% and progestin receptor (> 10 fmol/mg cytosol protein) in 60.5% of all the samples studied. The receptors were simultaneously present in 57.2%, estrogen receptor only in 20.8%, progestin receptor only in 3.3%, while both receptors were absent in 18.7% of the whole material. In samples from 253 premenopausal patients, measurable ER was found less frequently (71.1% of cases) and its concentration was lower (39.9 ± 5.1 fmol/mg cytosol protein, mean ± SEM) than in 502 postmenopausal patients (82%; 148.2 ± 11.6 fmol/mg). The frequencies of ER-positive samples and ER concentration were rather similar in primary and metastatic lesions, whereas PR was more often present (64 versus 47%) and its concentrations significantly higher (151.2 ± 12.5 versus 102.6 ± 21.1 fmol/mg) in primary than in metastatic tumors. When present simultaneously, there was a significant correlation between ER and PR concentrations in both primary and metastatic lesions independent of the menopausal status of the patient. ER concentration correlated significantly with age in both pre- and postmenopausal patients, while PR concentration correlated with age only in postmenopausal patients. The group with the highest ER values (above 100 fmol/mg cytosol protein) had a significantly lower serum estradiol concentration that the other patients. Serum estradiol values had a significantly positive correlation with cytosol PR content in the samples with a measurable PR. Serum progesterone, FSH, LH and prolactin did not correlate with tumor ER or PR concentrations. We conclude that concomitant assays of ER and PR from a breast carcinoma specimen provide a correct picture of the endocrine characteristics of the tumor independently of the serum concentrations of estradiol, progesterone, FSH, LH and prolactin.     

Hormone receptors do not predict the HER2/neu status in all age groups of women with an operable breast cancer.

BACKGROUND: In breast cancer, there is an inverse relationship between HER2/neu overexpression and receptors for estrogen (ER) or progesterone (PR). Some clinical observations such as the age-related association between hormone receptors and tumour grade, which predicts HER2/neu overexpression, suggest an age-related relationship. PATIENTS AND METHODS: Our study population consisted of 1362 consecutive women receiving primary surgery for non-metastatic invasive breast cancer. We compared the relationship between both hormone receptors and HER2/neu overexpression in different age groups taking other tumour characteristics into account. RESULTS: In a multivariate model, considering the overall group, a negative ER, a negative PR and a high tumour grade were predictive for HER2/neu overexpression (P <0.001). Considering 246 women aged < or =45 years, the only predictor for HER2/neu overexpression in this age category was a high tumour grade (P = 0.003). Considering the 1116 women aged >45 years, ER (P = 0.001), PR (P = 0.001) and tumour grade (P <0.001) were associated with HER2/neu (P <0.001). CONCLUSION: Our findings indicate that the association between ER, PR and HER2/neu overexpression varies with age. The hormone receptors are not an independent predictor for the HER2/neu status in young women while they are in elder patients.     

Variation of estrogen and progesterone receptor status in breast cancer after tamoxifen therapy

In the present paper we have studied the quantitative variations in estrogen (ER) and progesterone receptor (PR) content of breast cancer induced by tamoxifen. In addition to receptors, hormonal levels of estradiol, progesterone, prolactin, FSH, LH and testosterone were also measured. The cases included in our study were consecutively selected among those breast cancers in which an aliquot of the tissue sample sent for analysis of the steroid receptors was positive for cancer and also found to have at least one of the steroid receptors positive, not only in the biopsy but also in the surgical specimen. Following this criterion, we finally collected 14 cases of breast cancer treated daily with 30 mg of tamoxifen during an interval of 3 weeks from the initial biopsy to the final surgery. From our results we can conclude that tamoxifen reduced significantly the ER concentration while no changes were observed in PR values. Concerning hormones, while in premenopausal patients tamoxifen induced a rise in plasma estradiol, in postmenopausal women the only modification observed was a decrease in plasma FSH. The variation in steroid receptor content under tamoxifen therapy may also contribute to the evaluation of the hormone dependency of gynecologic malignancies.     

抗苗勒管激素用于评价戈舍瑞林对年轻乳腺癌患者卵巢功能抑制作用的前瞻性临床研究

目的:探讨抗苗勒管激素用于评价戈舍瑞林对年轻乳腺癌患者卵巢功能抑制的可行性.方法:选取激素受体阳性的术后、化/放疗后年轻乳腺癌患者40例,随机分为戈舍瑞林+他莫昔芬组(简称戈舍瑞林组)20例,他莫昔芬组20例(对照组).戈舍瑞林组在戈舍瑞林注射前1 d及注射戈舍瑞林3、6、12针后测定血清雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)及抗苗勒管激素(AMH)水平.对照组在相应时间段内进行检测.并对比两组不良反应发生率.结果:治疗前两组血清E 2、FSH、LH及AMH水平差异无统计学意义(P均>0.05).治疗后戈舍瑞林组的3个不同时间段血清E 2、FSH、LH及AMH水平均低于对照组水平(P均<0.05).戈舍瑞林组发生不良反应10例(50.0%),对照组6例(30.0%),主要不良反应为恶心、潮热、盗汗、性欲减退、阴道干涩、关节痛、骨质疏松等,均为Ⅰ-Ⅱ级.两组不良反应发生率差异无统计学意义(P>0.05).结论:抗苗勒管激素可以用于评价戈舍瑞林对年轻乳腺癌患者卵巢功能的抑制作用.     

Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease

Cumulative exposure to estrogen (E) and progesterone (P) over the menstrual cycle significantly influences the risk of developing breast cancer. Despite the dogma that PR in the breast merely serves as a marker of an active estrogen receptor (ER), and as an inhibitor of the proliferative actions of E, it is now clear that in the breast P increases proliferation independently of E action. We show here that the progesterone receptor (PR) and ER are expressed in different epithelial populations, and target non-overlapping pathways in the normal human breast. In breast cancer, PR becomes highly correlated with ER, and this convergence is associated with signaling pathways predictive of disease metastasis. These data challenge the established paradigm that ER and PR function co-operatively in normal breast, and have significant implications not only for our understanding of normal breast biology, but also for diagnosis, prognosis and/or treatment options in breast cancer patients.