三苯氧胺对围绝经期乳腺癌患者子宫内膜影响及宫腔镜的诊断价值

摘 要:［目的］ 分析围绝经期乳腺癌患者服用三苯氧胺(TAM)对子宫内膜的影响,并评价宫腔镜对子宫内膜病变的诊断价值。［方法］ 回顾性分析104例服用TAM的围绝经期乳腺癌患者资料。所有患者行病理组织活检、阴道超声及宫腔镜检查。［结果］ 病理结果显示正常子宫内膜21例,子宫内膜增生22例,子宫内膜息肉39例,子宫肌瘤/腺肌瘤17例,子宫内膜不典型增生2例,子宫内膜癌3例。宫腔镜检查诊断正常子宫内膜21例,子宫内膜增生21例,子宫内膜息肉40例,子宫肌瘤20例,子宫内膜癌2例,各病理类型宫腔镜检查与病理诊断符合率分别为100%、95.5%、97.5%、85.0%、66.7%。阴道超声检测显示,服用TAM ≤12个月、12～24个月、24～36个月、36～48个月、48～60个月和＞60个月患者的子宫内膜厚度分别为8.35mm、8.80mm、9.99mm、10.14mm、11.12mm和11.33mm,与用药＜2年患者相比,≥2年者内膜厚度明显增加（P＜0.05）。［结论］ 围绝经期乳腺癌患者长期服用TAM可能可引起子宫内膜病变。宫腔镜在子宫内膜病变诊断中有重要价值。     

SERMs和AIs对绝经后乳腺癌患者子宫内膜的影响

目的 观察选择性雌激素受体调节剂(selective estrogen receptor modulators,SERMs)和芳香化酶抑制剂(aromatase inhibitors,AIs)两类药物对绝经后乳腺癌患者子宫内膜的影响.方法 采用阴道B型超声监测50例绝经后乳腺癌患者在服药0、3、6、12月时子宫内膜的变化.结果 SERMs组服药3月后子宫内膜厚度大于AIs组(P＜0.05),服药6月和12月时较对照组明显增加(P＜0.01).AIs组服药3月和6月时子宫内膜厚度明显小于对照组(P＜0.01).结论 SERMs促进绝经后子宫内膜增生,AIs对绝经后子宫内膜增生有抑制作用；长期服用他莫昔酚需要定期监测子宫内膜.     

服用他莫西芬发生子宫内膜癌的临床特点及雌激素受体表达

目的:研究因乳腺癌服用他莫西芬(tamoxifen,TAM)而发生子宫内膜癌的临床特征及雌激素受体的表达,并探讨其发病机制。方法:回顾性分析33例因乳腺癌服用他莫西芬发生子宫内膜癌患者的临床资料,设为研究组(TAMET组),将同期普通子宫内膜癌患者50例设为对照组(ET组)。免疫组化法检测癌组织雌激素受体ERα、ERβ的表达。结果:TAMET组多为高分化腺癌,组织学分化好,病理分期早;绝经前期2组ERα、ERβ表达差异无统计学意义,绝经期TAMET组ERα、ERβ表达高于ET组,差异有统计学意义(P<0.05)。结论:绝经期2组内膜癌的发生机制不同,TAM可能主要是ERβ参与TAMET的形成。     

三苯氧胺与乳腺癌患者子宫内膜病理改变的非随机性临床观察

目的：随访口服三苯氧胺的乳腺癌患者，观察在随访期内发生的子宫内膜病理改变类型。方法：80例乳腺癌患者口服三苯氧胺20mg/日，每隔6个月作双合诊检查及子宫内膜活体组织检查。结果：可评价患者共67例，共行200次子宫内膜活检，60例仍为正常子宫内膜表现，TAM应用中位持续时间30个月，2例绝经前患者子宫内膜活检表现为单纯性增生过长，1例绝经后患者表现为萎缩性子宫内膜与复合性增生过长并存，1例绝经后患者切除子宫，术后内膜病是表现为增生性息肉、单纯必囊性增生。7例患者发生子宫内膜息肉，结论：长期口服三苯氧胺在绝经前后患者中均能发生子宫内膜单纯增生过长，复合性增生过长及息肉改变，未见有癌的发生。     

乳腺癌患者应用三苯氧胺导致子宫及子宫内膜病变的早期诊断及治疗

目的观察乳腺癌患者长期服用三苯氧胺对子宫及子宫内膜的影响，并探讨子宫内膜增生的诊断和治疗。方法41例服用三苯氧胺的绝经后女性乳腺癌患者入组，定期行阴道B超。发现子宫内膜厚度≥8mm者行子宫内膜病理检查，并应用不同剂量的甲羟孕酮来治疗子宫内膜增生，甲羟孕酮10mg，每日1次，共10天，或倍恩片0．25g每日1次，共10天。结果应用阴道超声发现子宫内膜厚度≥8mm者共15例，8例行诊断性刮宫，子宫内膜增生6例。应用甲羟孕酮后增生的子宫内膜脱落，不同剂量的甲羟孕酮疗效无差异。本组发现子宫肌瘤6例，其中3例TAM治疗前存在子宫肌瘤，TAM治疗后使子宫肌瘤迅速增大和个数增多，另3例在TAM治疗后出现子宫肌瘤。结论长期服用三苯氧胺可使子宫内膜增生，应采用阴道超声定期检测。甲羟孕酮可使增生的子宫内膜脱落。     

子宫内膜厚度在绝经后妇女子宫内膜癌中的诊断价值

[目的]评价子宫内膜厚度在绝经后妇女子宫内膜癌中的诊断价值。[方法]对150例绝经后阴道出血患者子宫内膜病变行阴道彩色多普勒超声检查,分析超声图像下子宫内膜厚度、血流指数。[结果]子宫内膜癌患者的子宫内膜厚度平均为8.43±4.76mm,显著性大于子宫内膜炎（4.04±2.55mm）,子宫内膜增生（5.16±2.78mm）和正常子宫内膜厚度（3.94±2.43mm）,差异均有统计学意义（P〈0.05）。在子宫内膜癌中RI〉0.4者比例为34.48%（10/29）,而在其他良性子宫内膜疾病及正常内膜组中的比例为97.52%（118/121）（χ^2=74.275,P=0.000）。[结论]子宫内膜厚度、内膜的血流特征有助于鉴别绝经后阴道流血的妇女中内膜的良恶性。     

血脂异常与子宫内膜癌的相关性分析

目的:回顾性分析子宫内膜癌患者中血脂代谢异常发病情况并探讨血脂代谢异常与子宫内膜癌发病风险的相关性。方法:收集2010年至2014年就诊于新疆医科大学第一附属医院的未经过放疗及化疗的且 经病理确诊为雌激素依赖型子宫内膜癌的病例81例。另以子宫内膜正常组,子宫内膜增生组作为对照组、各组分别56例,收集患者和对照者一般资料,既往史,月经史,婚育史,用药史,家族史(包括家族肿瘤史),生化血脂结果,病理结果。结果:子宫内膜正常组、子宫内膜增生组、子宫内膜癌组三组在发病年龄、月经状态、孕产情况、糖尿病发病情况、肿瘤家族史、PCOS/甲减发病率、HRT/TAM使用情况之间差异无统计学意义（P＞0.05）;子宫内膜癌组的体重指数（BMI）、甘油三酯（TG）、总胆固醇（TC）、高血压发病率均高于子宫内膜正常组、增生组,差异有统计学意义（P＜0.05）;子宫内膜癌组的高密度脂蛋白（HDL）明显低于子宫内膜正常组、增生组,差异有统计学意义（P<0.05）。 结论:子宫内膜癌患者的BMI、TG、TC、HDL及高血压发病率明显高于非子宫内膜癌患者,血脂异常很可能是子宫内膜癌发生的关键因素,有望高血脂将可能作为尽早识别子宫内膜癌高危人群的预警指标。     

他莫昔芬对乳腺癌患者卵巢的影响

他莫昔芬(tamoxifen,TAM)作为一种非类固醇类抗雌激素药物,自70年代初开始应用于治疗乳腺癌以来,已作为乳腺癌术后辅助治疗和预防复发的主要用药[1]。但长期服用TAM的乳腺癌患者常潜在妇科并发症,我们对我院2000年1月至2004年12月102例服TAM治疗的绝经前后乳腺癌妇女卵巢囊肿发生情况进行分析并探讨对策。1材料和方法1.1研究对象观察组:乳腺癌患者102例,年龄26~75岁,平均年龄59岁。绝经前31例,绝经后71例。对照组:乳腺癌患者46例,年龄32~73岁,平均年龄57岁,绝经前26例,绝经后20例。1.2TAM治疗观察组:口服TAM10mg,一日2次。TAM治疗时…     

经阴道超声诊断绝经后子宫内膜病变应用价值

目的：探讨经阴道彩色多普勒超声对绝经后妇女子宫内膜病变的诊断价值。方法：对125例绝经后出现阴道出血症状患者的子宫内膜声像图及彩色多普勒血流显像进行回顾性分析。所有病灶以子宫内膜活检或刮宫病理证实。结果：经阴道彩色多普勒超声子宫内膜息肉诊断符合率为86.57％（58/67）,子宫内膜增生过长诊断符合率为90.00％（27/30）,子宫内膜癌诊断符合率为82.35％（14/17）,病灶内RI值平均为0.42     

GnRh对乳腺癌根治术后口服他莫昔芬患者子宫内膜的保护研究

目的探讨促性腺激素释放激素激动剂(GnRh)对乳腺癌根治术后口服他莫昔芬(TAM)患者子宫内膜的保护作用。方法选取2016年3月至2017年6月间复旦大学附属华山北院收治的89例乳腺癌根治术后患者,采用随机数字表法分为试验组44例和对照组45例。试验组患者采用术后口服TAM+肌肉注射达菲林治疗,对照组患者采用单纯口服TAM治疗。比较两组患者治疗前后促卵泡生成素(FSH)、雌二醇(E2)和黄体生成素(LH)水平及组织病理改变,采用阴道B超于治疗后3、6和12个月记录两组患者子宫内膜变化情况。结果对照组患者治疗后3、6和12个月,子宫内膜厚于治疗前,差异均有统计学意义(均P <0. 01),试验组患者子宫内膜薄于治疗前及对照组,差异均有统计学意义(均P <0. 05)。治疗后,对照组患者FSH和LH水平均高于治疗前,E2水平低于治疗前试验组患者FSH、E2和LH水平均低于治疗前及对照组,差异均有统计学意义(均P <0. 05)。治疗后,试验组患者子宫内膜增生率为9. 1%,子宫内膜息肉发生率为0. 0%,均低于对照组的35. 6%和11. 1%,差异均有统计学意义(均P <0. 05)。随访12个月,试验组患者未见阴道不规则出血,对照组出现3例(6. 7%)少量阴道不规则出血患者,差异无统计学意义(P> 0. 05)。结论乳腺癌根治术后,患者口服TAM化疗并应用GnRHa不仅能减少子宫内膜病理改变,还可阻止卵巢功能受损,有临床应用价值。     

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。     

Uterine Malignancy following Tamoxifen Use in Breast Cancer Patients in Iran: Case Series and Literature Review

Background: This study evaluated tumor characteristics and survival in women with breast cancer whosubsequently developed uterine cancer. Methods: Information about endometrial cancer in tamoxifen usersfollowing breast cancer refered to the gynecologic oncology clinic of Vali-Asr hospital between 1997-2007 wasevaluated. Results: Among 330 patients with endometrial cancer, 5 were in women previously diagnosed withbreast cancer. Two cancers were malignant mixed Mullerian tumors of the uterus (MMMT), 2 were endometrioidadenocarcinomas, and one was a papillary clear cell carcinoma. Patients received tamoxifen for 4-8 years. Theendometrial cancers occurred 2-11 years after initial treatment for the breast cancers. Four of the endometrialcancers featured abnormal uterine bleeding and one of them had increased vaginal discharge and all werediagnosed on endometrial curetting. All patients received standard surgical staging for endometrial cancer andall except one were stage I. At laparotomy of one patient, an advanced stage MMMT was found with diffusedperitoneal spread and ascites. In spite of the surgery, she died of disease, 3 months later. The other patientsremain recurrence-free for breast cancer and uterine cancer after 6-120 months. Conclusion: Breast cancerpatients who use tamoxifen and have early stage endometrial cancers demonstrate a good prognosis. Abnormaluterine bleeding or vaginal discharge is the most important symptom.     

Indication of hysteroscopy in tamoxifen treated breast cancer patients

The aim of this study was to indicate the patients treated with tamoxifen for breast cancer in which hysteroscopy with biopsy should be considered mandatory. 414 breast cancer patients who underwent hysteroscopy with bioptic evaluation were enrolled in the study. 334 subjects were treated with 20 mg of tamoxifen daily as adjuvant therapy for six up to a hundred months. Of the remaining 80 control patients, which had not received tamoxifen, 30 were in premenopause (Group IA) and 50, in postmenopause (Group IIA). The tamoxifen-treated patients were subdivided in premenopausal (Group IB = 72 patients) and in postmenopausal (Group IIB = 262 patients) groups. All patients were further classified in asymptomatic or symptomatic groups considering whether uterine bleeding was absent or present. The evaluation of the endometrial mucosa was performed by office hysteroscopy. In group IIB patients presenting uterine bleeding, malignant lesions were found in 7.8% of the cases. The incidence of premalignant and malignant lesions in IIB patients treated for longer than 3 years (11.7%) was higher than that observed in IIB patients treated for less than 3 years (1.3%). There was a significant difference in terms of endometrial pathology between Group IIB (32.8%) and Group IIA (8%) (p < 0.001); and between Group IIB (32.8%) and Group IB (13.9%) women (p = 0.003). Among IA and IIA patients there were no cases of endometrial hyperplasia or cancer; on the contrary, in IB and IIB women, 2 and 22 cases of atypical hyperplasia were observed, respectively. All cases of endometrial cancer were observed in Group IIB and had a diagnosis of poor prognosis. In conclusion the hysteroscopy with biopsy should be considered the first diagnostic procedure to perform in tamoxifen-treated postmenopausal patients presenting uterine bleeding and in postmenopausal women treated for longer than 3 years. In premenopause, hysteroscopy should be proposed to women with ultrasonographic abnormalities and/or with uterine bleeding to patients at high risk for endometrial cancer.     

The effect of tamoxifen on the endometrium

Summary Tamoxifen is one of the most important treatments for breast cancer, especially in postmenopausal patients. It acts primarily as an anti-estrogenic agent, due to its cytoplasmic estrogen receptor binding capacity. However, it also exerts a mild estrogenic effect. Since the prolonged use of estrogen has been reported to increase the rate of benign and malignant changes in the endometrium, we evaluated whether there is a correlation between tamoxifen therapy and endometrial benign and malignant conditions. The study group comprised 95 patients with breast cancer who were treated with tamoxifen. No control group was examined. Patients underwent vaginal ultrasonography and endometrial biopsy in order to evaluate any changes in the endometrium occurring during tamoxifen therapy. Pathological changes were observed in 14 patients, 13 of whom were treated with tamoxifen for more than 12 months. Of these women, 3 were diagnosed with endometrial cancer, 3 had mild dysplasia, 3 had endometrial hyperplasia, and 4 had a benign endometrial polyp. Our findings indicate a significant correlation between long-term tamoxifen administration and endometrial proliferation. We therefore recommend that women treated with tamoxifen for more than 12 months have an annual vaginal ultrasonography and endometrial biopsy.     

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     

Outcomes in patients with primary breast cancer and a subsequent diagnosis of endometrial cancer : comparison of cohorts treated with and without tamoxifen

BACKGROUND: The study compared tumor characteristics and survival in women with breast cancer who subsequently developed endometrial cancer with or without a history of tamoxifen use. METHODS: The British Columbia Cancer Agency registry identified 163 women diagnosed with breast cancer between 1989-1999 who received a subsequent diagnosis of endometrial cancer. Of these, 55% (n = 90) had a history of tamoxifen use. Outcomes analyzed were breast cancer-specific survival (BCSS), endometrial cancer-specific survival (ECSS), and overall survival (OS). RESULTS: Median follow-up was 9.4 years. Distributions of age, menopausal status, body mass index, and comorbidities were similar in the tamoxifen-treated and nontamoxifen cohorts. Proportions of aggressive endometrial cancer subtypes including papillary serous, clear cell, and mixed mullerian tumors were higher in the tamoxifen cohort (28% vs14%, P = .03). Distributions of endometrial cancer grade and stage were similar in the 2 groups (P > .05). Hysterectomy and/or oophorectomy were the primary treatments for endometrial cancer in 99% of patients, with comparable pelvic control rates in the tamoxifen and nontamoxifen groups. At 10 years, patients in the tamoxifen group experienced lower BCSS compared with the nontamoxifen group (89% vs 97%, P = .02). No significant differences in ECSS and OS were observed between the 2 groups (ECSS 82% and 82%, P = .85; and OS 69% v. 66%, P = .85). CONCLUSIONS: In patients with breast cancer who developed a subsequent endometrial cancer, tamoxifen-treated patients had higher proportions of aggressive endometrial cancer subtypes, but almost all cases were amenable to surgery, thus resulting in similar endometrial cancer control and survival when compared with nontamoxifen treated patients.     

Postoperative chemo-endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor-positive stage II breast cancer. Nishinihon Cooperative Study Group of Adjuvant Therapy for Breast Cancer

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991. we studied the effects of postoperative adjuvant therapy for Japanese women with stage 11 breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER- tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER- patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease-free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments <0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P<0.01). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.     

Tamoxifen and the endometrium: findings of pelvic ultrasound examination

The need for endometrial surveillance in breast cancer patients undergoing adjuvant treatment with tamoxifen is still controversial. In this study, 164 asymptomatic breast cancer patients (110 on treatment with tamoxifen, 20 mg/day, and 54 controls) were examined with pelvic ultrasound and endometrial biopsy. No differences in ultrasound and biopsy findings were observed in the pre- and perimenopausal group between patients treated with tamoxifen and controls. Postmenopausal patients on tamoxifen had a significantly thicker endometrium (mean ± SD, 7.2 ± 8.5 vs. 1.5 ± 4.3 mm, p=0.00002) and significantly larger uterine volume (mean ± SD, 63.2 ± 39.9 vs. 43.7 ± 38.8 cm³, p=0.0001) than controls. Fifty-four percent of patients on tamoxifen had an endometrial thickness 5 mm, often with multiple irregular sonolucencies suggesting the presence of cysts. Ultrasound findings, however, did not correlate with the presence of endometrial abnormalities on biopsy, and no endometrial cancer or atypical hyperplasia were found. This lack of correlation makes questionable the use of routine sonography in asymptomatic breast cancer patients on tamoxifen. Obtaining routine endometrial samples, on the other hand, may be difficult in some patients because of cervical stenosis or refusal. Until the benefits of endometrial surveillance will be proved, asymptomatic patients should not be submitted routinely to ultrasound examination or biopsy, but encouraged to report promptly any abnormal vaginal bleeding.