Use of hormone therapy for menopausal symptoms and quality of life in breast cancer survivors. Safe and ethical?

Breast cancer is the most prevalent cancer in women and presently, the breast cancer survivors are an important group of women that faced the several consequences of estrogen deficiency, which is especially common in women after chemotherapy. The most bothersome is the vasomotor symptoms, which are effectively relieved by hormonal therapy (HT). Also, the increased risk of osteoporosis and coronary artery disease is major problem to be resolved in pos of maintaining a good quality of life. Fearing cancer recurrence, most physicians do not offer HT to women with a history of breast cancer. Over this issue reviews the available evidence of the use of HT and tibolone in women treated for breast cancer.     

Qualitative cross-cultural exploration of vaginal bleeding/spotting symptoms and impacts associated with hormone therapy in post-menopausal women to inform the development of new patient-reported measurement tools

Objectives

To understand the vaginal bleeding/spotting experiences of postmenopausal (PM) women taking estrogen plus progestin therapies (EPT) and develop measures to assess these symptoms and their impact on women's daily lives in four countries.

Design

(1) Concept elicitation interviews were conducted with PM women in the US (n = 14), Italy (n = 15), Mexico (n = 15) and China (n = 15) to explore vaginal bleeding/spotting symptoms associated with EPT. The Post-Menopausal Bleeding Questionnaire (PMBQ) was also debriefed to evaluate understanding and comprehensiveness. (2) Based on concept elicitation, a single item electronic daily diary was developed and the PMBQ modified to form a 12-item impact measure. (3) The measures were pilot-tested and then cognitively debriefed with US women receiving EPT. All qualitative data was subject to thematic analysis.

Main outcome measures

The Vaginal Bleeding/Spotting Daily Diary, (VBS-DD) and Post-Menopausal Bleeding Impact Questionnaire (PMBIQ) were developed in this study.

Results

Concept elicitation identified vaginal bleeding and spotting as important symptoms for women taking EPT, impacting their emotional wellbeing, social life, ability to move freely, clothing and sexual activity. Based on pilot testing and cognitive debriefing, women demonstrated good understanding of the VBS-DD and the PMBQ was reduced to 10 items due to conceptual redundancy.

Conclusions

Women taking EPT in the US, China, Mexico and Italy reported vaginal bleeding/spotting symptoms that have a detrimental impact on their quality of life. Two new measures were developed to assess the severity and impact of vaginal bleeding/spotting specific to EPT. This work highlights the need for EPT-related symptoms to be a part of treatment decision-making.     

孕激素的临床药理基础

孕激素制剂种类繁多、应用广泛。为安全、合理、有效、经济地应用此类药物,本文综述孕激素的临床药理作用、制剂分类及常用孕激素的药理学和药物代谢动力学特点。     

表皮生长因子受体信号通路在人子宫内膜癌移植瘤孕激素耐药机制中的作用

目的 建立人子宫内膜癌皮下移植瘤孕激素耐药模型,探讨表皮生长因子受体（EGFR）下游信号通路在子宫内膜癌孕激素耐药机制中的作用。方法 分别利用人子宫内膜癌孕激素敏感型Ishikawa细胞株和孕激素不敏感型Ishikawa-pLWERNL细胞株制备裸鼠皮下移植瘤模型（每组18只）;成瘤后,分别将接种Ishikawa细胞株和接种Ishikawa-pLWERNL细胞株的裸鼠各自分成3组（每组6只）,分别给予甲羟孕酮（MPA组）、吉非替尼（吉非替尼组）、生理盐水（对照组）。疗程结束后称取各组肿瘤湿重,采用Western blotting法检测肿瘤组织中EGFR、孕激素受体B（PR-B）、ERK1/2、p-ERK1/2、AKT及p-AKT蛋白的表达。结果 在接种Ishikawa细胞株的裸鼠中,MPA组、吉非替尼组移植瘤湿重与对照组相比,分别减轻43.0%和31.5%,差异有统计学意义（P均<0.05）。在接种Ishikawa-pLWERNL细胞株的裸鼠中,吉非替尼组移植瘤湿重与对照组相比,减轻35.7%,差异有统计学意义（P<0.05）;而MPA组移植瘤湿重与对照组相比,减轻2.9%,差异无统计学意义（P>0.05）。接种Ishikawa-pLWERNL细胞株的裸鼠移植瘤EGFR蛋白表达明显高于接种Ishikawa细胞株的裸鼠移植瘤（P<0.05）,而PR-B蛋白表达则明显低于接种Ishikawa细胞株的裸鼠移植瘤（P=0.000）。接种Ishikawa细胞株的裸鼠移植瘤中,MPA组PR-B蛋白表达明显低于对照组（P<0.01）,而吉非替尼组与对照组的差异无统计学意义（P>0.05）;在接种Ishikawa-pLWERNL细胞株的裸鼠移植瘤中,各组PR-B蛋白表达水平比较差异均无统计学意义（P>0.05）。在接种Ishikawa细胞株的裸鼠移植瘤中,吉非替尼组p-ERK1/2、p-AKT蛋白表达均低于对照组和MPA组,差异有统计学意义（P<0.05）;而在接种Ishikawa-pLWERNL细胞株的裸鼠移植瘤中,吉非替尼组p-ERK1/2、p-AKT蛋白表达低于对照组,MPA组p-ERK1/2、p-AKT蛋白表达高于对照组,差异均有统计学意义（P<0.05,P<0.01）。结论 在接种孕激素不敏感型Ishikawa-pLWERNL细胞株产生的移植瘤中,过表达的EGFR可下调PR-B蛋白表达,而对MPA不敏感;EGFR受体酪氨酸激酶拮抗剂吉非替尼可有效抑制p-ERK1/2和p-AKT的表达,尤其对接种Ishikawa-pLWERNL细胞株产生的移植瘤效果更显著。     

子宫内膜癌分子标志物与临床病理特征关系的研究

目的探讨子宫内膜癌中ER、PR、PTEN、p53及Ki-67的表达与临床、病理特征的关系。方法收集200例原发性子宫内膜癌患者的临床病理资料，对其ER、PR、PTEN、p53及Ki-67表达情况进行统计学分析。结果①子宫内膜癌病例中．ER、PR、PTEN、p53的阳性表达率分别为86．5％、85．5％、82．10和49．2％；Ki-67在癌灶中的阳性表达率为4％--95％，平均为46．9％。②妊娠次数与PR阳性表达呈负相关（r=-0．191，P=0．007），而发病年龄、分娩次数与p53阳性表达呈正相关（r=0．184，P=0．041；r=0．255，P=0．004）。③子宫内膜样腺癌ER、PR、p53阳性率与其他类型子宫内膜癌比较，差异有统计学意义（P〈0，01）。④ER阳性表达与手术病理分期呈负相关（r=-0．155，P=0．028），其中I期患者ER阳性率高于Ⅱ期及以上患者（P=0．032）。⑤ER、PR阳性表达与组织学分级呈负相关（r=-0．217，P=0．002；r=-0．317，P=0．000），但p53、Ki-67表达与其呈正相关（r=0．327，P=0．000；r=0．465，P=0．000）。⑥ER阳性表达与肌层浸润深度呈负相关（r=-0．142，P=0．046），在有无深肌层浸润上ER、PR表达率均有统计学意义（P〈0．05）。结论对子宫内膜活检组织进行分子标志物的分子特征检测，有助于指导临床。     

Current breast cancer risks of hormone replacement therapy in postmenopausal women

The controversies surrounding hormone replacement therapy have left many women confused and afraid. Providers have been faced with long-standing assumptions challenged by an abundance of new data in the past few years, with little guidance on how to interpret these findings. The objective of this paper is to provide a framework for understanding breast cancer risk associated with postmenopausal hormone replacement therapy, with a particular focus on how observational studies and randomised trials provide complementary information. This framework considers the data on risks of various hormonal preparations, the profiles of women at risk, and ends with an expert opinion in this context.     

The differential association of conjugated equine estrogen and esterified estrogen with activated protein C resistance in postmenopausal women

OBJECTIVES: Clinical trials have demonstrated that oral conjugated equine estrogen (CEE) therapy with or without medroxyprogesterone (MPA) increases venous thrombotic risk but this safety issue has not been investigated for other oral estrogens. Based on observational study findings that esterified estrogen (EE) was not associated with venous thrombotic risk whereas CEE was, we hypothesized that CEE users would be more resistant to activated protein C (APC), a prothrombotic phenotype, than EE users. METHODS: We conducted an observational, cross-sectional study of postmenopausal women 30-89 years old who were controls in a case-control study of venous thrombosis. Use of CEE, EE, and MPA at the time of phlebotomy was determined using computerized pharmacy records. APC resistance was measured in plasma by the endogenous thrombin potential normalized APC sensitivity ratio. Adjusted mean APC resistance values were compared across estrogen type and CEE:EE ratios are presented. RESULTS: There were 119 CEE and 92 EE users at the time of phlebotomy. Compared with EE users, CEE users had APC resistance measures that were 52% higher (1.52; 95% confidence intervals: 1.07-2.17) in adjusted analyses. Restricting to modal dose users (0.625 mg) and stratifying by MPA use did not materially change associations. CONCLUSIONS: CEE use was associated with higher levels of APC resistance when compared with EE use in postmenopausal women. These findings might provide an explanation for the higher risk of venous thromboembolism previously observed with CEE compared with EE use and, if replicated, may have safety implications for women when choosing an estrogen for symptom relief.