The risk of breast cancer in postmenopausal women who have used estrogen replacement therapy

We studied the association between estrogen replacement therapy (ERT) and the risk of breast cancer as part of the Cancer and Steroid Hormone Study. All subjects in the analysis were postmenopausal women enrolled from eight geographic areas. Women 25 to 54 years old with newly diagnosed breast cancer were identified through population-based tumor registries and diagnosed between Dec 1, 1980, and Dec 31, 1982. Controls were selected from the same eight geographic areas by the random digit dialing of residential telephone numbers. Analyses included 1369 cases and 1645 controls. Among women with bilateral oophorectomy, the relative risk of breast cancer for women who had ever used ERT was 1.3, compared with women who had never used ERT. Among women who had undergone hysterectomy but who still had at least one ovary, the relative risk was 1.1; among women who reported a natural menopause, the relative risk was 0.8. Overall, the risk of breast cancer did not appear to increase appreciably with increasing ERT duration or latency, even for durations and latencies of 20 years or longer.     

Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk

CONTEXT: Whether menopausal hormone replacement therapy using a combined estrogen-progestin regimen increases risk of breast cancer beyond that associated with estrogen alone is unknown. OBJECTIVE: To determine whether increases in risk associated with the estrogen-progestin regimen are greater than those associated with estrogen alone. DESIGN: Cohort study of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. SETTING: Twenty-nine screening centers throughout the United States. PARTICIPANTS: A total of 46355 postmenopausal women (mean age at start of follow-up, 58 years). MAIN OUTCOME MEASURE: Incident breast cancers by recency, duration, and type of hormone use. RESULTS: During follow-up, 2082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years (relative risk [RR], 1.2 [95% confidence interval [CI], 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the relative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrogen-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-progestin-only use among recent users, after adjustment for mammographic screening, age at menopause, body mass index (BMI), education, and age. The P value associated with the test of homogeneity of these estimates was .02. Among women with a BMI of 24.4 kg/m2 or less, increases in RR with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. These associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only. CONCLUSION: Our data suggest that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone.     

Prolonged estrogen therapy in postmenopausal women

The therapeutic use of estrogens for more than 25 years made it possible to examine evidence of their safety and effectiveness in a study of 292 postmenopausal women who had undergone prolonged estrogen therapy. Diethylstilbestrol and conjugated equine estrogens have been used most frequently since 1945. The study showed that only 5% of patients necessitated discontinuation from severe side effects; the latter of the 2 compounds was tolerated without side effects among almost all patients. Hot flashes were completely relieved in 93 of 94 patients. Prolonged estrogen therapy was the treatment for postmenopausal osteoporosis in 119 patients, 103 of whom had suffered collapse of vertabrae. Either complete or significant relief from pain occurred in 90%. A group of 27 women showed evidence that estrogen is a prophylactic against postmenopausal osterporosis. Justification for the fear that mammary and cervical carcinoma may result from this therapy is absent. When combined with periodic pelvic and vaginal cytological examinations, prolonged cyclic oral estrogen therapy is safe and effective treatment for postmenopausal women with disabling symptoms or osteoporosis.     

雌激素替代疗法对绝经后妇女血清血管紧张素转化酶及血脂代谢的影响

目的:探讨雌激素替代疗法(ERT)对绝经后妇女血清血管紧张素转化酶(ACE)含量及血脂代谢的影响.方法:测定45例健康绝经后妇女应用ERT(治疗组)前及应用ERT14wk后血清ACE、雌二醇(E2)及血清三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDL-C)、脂蛋白(a)[Lp(a)]含量,并与45例健康绝经后妇女应用安慰剂(对照组)进行对照.结果:对照组应用安慰剂前后,ACE及血脂各项含量无变化;治疗组应用ERT后,ACE含量明显降低且与E2呈负相关,血清TC,LDL-C及Lp(a)含量降低,HDL-C含量升高,TG无变化.结论:绝经后妇女补充雌激素,可通过降低血清ACE水平及改善血脂代谢共同发挥对心血管系统的保护作用.     

雌激素替代治疗对绝经后妇女左心室舒张功能的影响

为评价雌激素替代治疗对绝经后妇女左心室舒张功能的影响，用多普勒超声心动图记录了４５例健康绝经后妇女二尖辨口多普勒血流频谱，其中２５例为雌激素（尼尔雌醇）替代治疗组，２０例为对照组。结果显示：二组间左心室舒张期充盈明显不同，尤其为替代治疗组Ｅ／Ａ比值高，ＡＦＦ低，替代治疗组舒张早期充盈量大于对照组。认为长期雌激素替代治疗可以影响左心室舒张功能     

雌激素替代治疗对绝经后特发性流出道室性心律失常的影响

目的:探讨性激素水平与绝经后女性特发性室性心律失常(IOTVA)的关系,并观察雌激素替代治疗对其影响.方法:检测绝经后女性正常组和IOTVA患者组血清性激素水平及室性心律失常数目;观察IOTVA组给予雌激素替代治疗后的效果.结果:IOTVA组雌激素水平较正常绝经后女性相比显著降低(8.4±3.4 vs 36.9±12....     

A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer

To quantify the effect of estrogen replacement therapy on breast cancer risk, we combined dose-response slopes of the relative risk of breast cancer against the duration of estrogen use across 16 studies. Using this summary dose-response slope, we calculated the proportional increase in risk of breast cancer for each year of estrogen use. For women who experienced any type of menopause, risk did not appear to increase until after at least 5 years of estrogen use. After 15 years of estrogen use, we found a 30% increase in the risk of breast cancer (relative risk, 1.3; 95% confidence interval [CI], 1.2 to 1.6). The increase in risk was largely due to results of studies that included premenopausal women or women using estradiol (with or without progestin), studies for which the estimated relative risk was 2.2 (CI, 1.4 to 3.4) after 15 years. Among women with a family history of breast cancer, those who had ever used estrogen replacement had a significantly higher risk (3.4; CI, 2.0 to 6.0) than those who had not (1.5; CI, 1.2 to 1.7).     

Pilot study of formestane in postmenopausal women with breast cancer

A pilot study of Formestane or 4-Hydroxyandrostenedione (Lentaron), a new endocrine agent, was conducted on 18 postmenopausal patients with locally advanced and metastatic breast cancer. 16 patients were evaluable for response and objective responses were seen in 4 patients (25%). Stabilisation of disease was seen in 5 patients (32%). Out of 17 patients evaluable for toxicity, 3 (18%) reported adverse effects including hot flushes, lethargy and myalgia. Adverse effects were mild, transient and no patient required discontinuation of drug. Our study confirms that Formestane is a well tolerated endocrine agent with low toxicity and reasonable efficacy in postmenopausal patients with locally advanced and metastatic breast cancer.     

对绝经后激素替代治疗的重新评价

激素替代治疗(HRT)因其可有效改善妇女围绝经期症状而得到广泛应用，但最近人们发现，长期应用HRT可增加心血管疾病的发生率及激素依赖性肿瘤发生的危险性。通过系统复习文献提出，HRT的应用须慎重。     

The postmenopausal estrogen/breast cancer controversy.

OBJECTIVE--To provide an overview of the postmenopausal estrogen/breast cancer controversy emphasizing the sources of disagreement in the literature and their clinical and research implications. DATA SOURCE AND SELECTION--A MEDLINE search of the English-language literature and a review of bibliographies of meta-analyses describing the association between postmenopausal estrogen use and breast cancer risk. DATA EXTRACTION--Twenty-four original articles and three meta-analyses were reviewed. In addition, five studies that attempted to minimize detection bias were reviewed to assess the potential role of this bias on risk estimates. DATA SYNTHESIS--Among the original articles, risk estimates ranged from a protective to an adverse effect in women who ever used estrogens; no consistent quantitative effects of estrogens on breast cancer risk were found. In the meta-analyses, summary risk estimates were not significantly elevated in women who ever used estrogen. Findings from European-based studies may account for the increased risk associated with increasing duration of use reported in one meta-analysis. In studies that controlled for detection bias, risk estimates were 1 or less in the ever-used category; there was no consistent effect across other categories of use. CONCLUSION--These findings do not support an overall increased risk of breast cancer in women who ever used postmenopausal estrogens or a conclusive or consistent effect across other measures of use. Cross-national differences in estrogen use and inequalities in breast cancer detection between estrogen users and nonusers may account for the increased risk estimates reported in some studies. Newer estrogen and progestin-opposed regimens need to be evaluated further.     

激素替代治疗对绝经妇女乳腺X线密度的影响

目的探讨不同方案激素替代治疗（HRT）对绝经妇女乳腺x线密度的影响及其临床意义。方法90例绝经后妇女随机分成3组：A组,每日结合雌激素（CEE）0．3mg＋孕激素醋酸甲羟孕酮（MPA）2mg＋钙尔奇D6001片;B组,每日CEE0．625mg＋MPA2mg＋钙尔奇D6001片;C绀,每日钙尔奇D6001片。用药1年,Wolfe和半定量法计算并比较j组乳腺X线密度及A、B绀用药前后乳腺X线密度的变化。结果用药1年,两种方法计算乳腺x线密度,三组中密度最高为B组,其次为A、C组,差异有统计学意义（P〈0．01）,A、B组乳腺x线密度分别与C绀比较,差异均有统计学意义（P〈0．ol或0．05）;B组乳腺x线密度较A组升高,但差异无统计学意义（P〉0．05）。A、B组用药前后自身比较,半定量法显示,A、B组用药后较用药前均增高（但前者P〉0．05,后者P〈0．01）;B组用药后增高程度较A组高,但两组间差异无统计学意义（P〉0．05）。结论HRT能增高乳腺x线密度,且增高程度可能与剂量相关,提示HRT对乳腺有不良反应,应用HRT宜选最小有效剂量。乳腺x线密度可作为HRT对乳腺影响的监测指标。     

冠心病妇女绝经后雌激素替代治疗对趋化因子受体CXCR2的影响

目的：探讨经雌激素替代治疗后的绝经后冠心病妇女外周血单核细胞趋化因子受体CXCR2的变化。方法：选22例已绝经的冠心病妇女为观察组,20例绝经后健康妇女作为对照组,两组受试又随机分为干预组和安慰剂组,干预组口服结合型雌二醇（倍美力）,每日0．625mg,连续3个月,安慰剂组口服安慰剂（维生素C）,观察对象均分别于用药前及用药3个月末抽血测血清雌二醇（E2）水平,外周血单核细胞趋化因子受体CXCR2蛋白表达水平。结果：（1）治疗前冠心病组血清E2,CXCR2蛋白水平显低于正常对照组（P＜0．01）;（2）经过雌激素干预治疗3个月后,绝经后妇女血清E2水平均显上升（P＜0．01）,外周血单核细胞趋化因子受体CXCR2水平均显下降（P＜0．01）,且冠心病组较对照组变化更明显;（3）血清E2水平与CXCR2水平变化呈显负相关（r=-0.46).结论：雌激素替代治疗后的绝经后妇女外周血单核细胞趋化因子受体CXCR2下调,且有冠心病变化更明显,提示与雌激素的心脏保护作用有关。     

超声影像学监测绝经后长期激素替代疗法对乳腺的影响

目的超声影像学方法监测长期激素替代疗法(HRT)对乳腺的影响.方法60例身体健康、绝经1～5年的妇女,随机分为4组,每组15例;采用周期联合方法分别给予含1.5或0.75 mg E2的经皮17-β E2凝胶与100 mg微粉化天然黄体酮(MP)或2 mg醋酸甲羟孕酮(MPA),睡前口服,每月连用25 d;HRT前及第2年后每年用乳腺超声观察双侧乳腺腺体层的厚度、导管宽度、小叶形态结构及彩色多普勒血流显像;于治疗周期的第15～25天取血,测定E2;作乳腺胀痛日记.结果 (1)HRT后乳腺腺体厚度高于HRT前,呈逐年上升的趋势;乳腺导管的宽度呈逐年下降的趋势,第5年与第6年比较有显著差异(P＜0.05).(2)新发生乳腺结构改变者共计22例,累积发生率41.5%.新生乳腺实性结节5例(8.3%),乳腺囊肿1例(1.7%);HRT第2年后有乳腺结构改变者的雌激素水平高于无改变者,第6年两者比较有显著性差异(P＜0.05);第2年后有乳腺结构改变者的腺体厚度高于无改变者,第5、6年两者比较有显著性差异(P＜0.05).(3)HRT后各年有乳腺胀痛者的雌激素水平高于无乳腺胀痛者,第2、6年两者间有显著性差异(P＜0.05).结论HRT后乳腺组织中的腺体成分有增加的趋势,发生乳腺结构改变者有血清雌激素水平升高及乳腺腺体厚度增加的趋势,发生乳腺胀痛者有血清雌激素水平升高的趋势.超声可用于监测HRT中乳腺结构改变及乳腺病变.