绝经激素治疗增加乳腺癌患病风险:Lancet最新文献解读

绝经激素治疗(menopausal hormone therapy, MHT)是否会增加乳腺癌的发病风险一直存在争议。2019年9月,Lancet发表了一篇荟萃分析,汇集了世界范围内关于MHT与乳腺癌发病风险的证据。此研究结果表明,除阴道应用雌激素外,所有方式应用MHT均增加乳腺癌发病风险,且该风险随MHT应用时间的延长逐渐升高。其中雌激素、孕激素联合治疗风险更高,停药后额外风险可持续10年以上。小剂量应用MHT或选择天然孕激素等并不能回避乳腺癌发病风险的增加。本文对该荟萃分析进行解读,强调应用MHT需考虑乳腺癌风险,全面评估患者风险与获益。     

中国绝经管理与绝经激素治疗指南(2018)

《中国绝经管理与绝经激素治疗指南(2018)》由中华医学会妇产科学分会绝经学组的全体专家在2012版指南基础上修订, 并采纳了国内相关学术领域专家的修改意见, 旨在指导医疗保健专业人士优化绝经过渡期及绝经后妇女的健康管理。本指南综合了本领域近年来的研究进展, 也借鉴了近几年全球各大绝经学会相应指南中的重要信息, 并纳入了证据水平和建议等级; 保留了2012版指南中的规范绝经激素治疗(menopause hormone therapy, MHT)诊疗流程, 并有所改进; 增加了绝经的分期系统——生殖衰老研讨会分期+10, 便于理解生殖衰老过程的临床、生物学、内分泌变化; 肯定了MHT的最佳适应证是治疗血管舒缩症状(vasomotor symptoms, VMS)、生殖泌尿道萎缩相关问题和预防绝经相关的低骨量及骨质疏松症。MHT的风险取决于药物类型、剂量、使用时间、管理方式、启动时间以及是否使用孕激素。MHT应依据现有最好的证据个体化进行, 定期重新评估是否继续或停止MHT, 以获得最大收益及最小风险。对年龄小于60岁或绝经10年内无MHT禁忌证的妇女, 针对VMS、骨量丢失和骨折, 启动MHT治疗的收益风险比最高。只要无禁忌证, 早发性卵巢功能不全患者应给予激素补充治疗至普通女性自然绝经的平均年龄, 之后按照绝经后MHT原则进行。     

早期乳腺癌辅助内分泌治疗进展

在癌症治疗中乳腺癌的激素治疗代表着最早期的分子疗法或靶向治疗。早期乳腺癌采用激素制剂辅助治疗,无论淋巴结状况如何都会减少疾病的复发率和死亡率。直到最近,对于雌激素受体或孕激素受体阳性的早期乳腺癌患者来说,术后口服5年的三苯氧胺仍然是一个重要的选择,芳香化酶抑制剂已经是标准治疗。最近的随机临床试验结果,使雌、孕激素受体阳性的早期乳腺癌术后5年的三苯氧胺治疗的金标准地位受到挑战,无论单用或化疗后使用都是如此。主要的问题有:①用药时限。术后五年的辅助治疗是否够长;②药物的转换。三苯氧胺治疗以后是否应后续使用芳香…     

绝经激素治疗的获益与风险

绝经激素治疗(menopausal hormone therapy,MHT)是对卵巢功能衰退的女性进行外源性雌激素补充以解决与雌激素不足相关的健康问题,MHT对于缓解绝经症状、防治泌尿生殖道萎缩相关疾病和预防骨质疏松的获益是毋庸置疑的.近80年来,医学界对MHT获益与风险的认识经历了跌宕起伏、崎岖发展的过程.特别是21...     

乳腺浸润性导管癌超声声像图特征与ER、PR表达的相关性研究

正乳腺癌是妇女最常见的恶性肿瘤之一,目前,尚无有效的预防措施,决定预后的关键是早期诊断和治疗。超声检查,是乳腺癌常用的检查方式。乳腺组织的生长和细胞的增殖均受雌激素、孕激素的调控,而当其发生癌变时,雌激素受体(ER)、孕激素受体(PR)发生相应的变化,尤其在浸润性导管癌中临床意义更大~([1])。然而,乳腺浸润性导管癌超声声像图特征与ER、PR表达是否存在相关性,目前研究报道尚少。本研究回顾分析36例乳腺浸润性导管     

乳腺癌组织中血管内皮生长因子与雌激素受体、孕激素受体及人类表皮生长因子的关系

目的探讨乳腺癌组织中人类表皮生长因子(VEGF)与雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子(Her-2)的关系,进而分析VEGF在乳腺癌各分子分型中的表达是否有差异性。方法应用免疫组化方法检测50例病理证实乳腺癌组织中VEGF、ER、PR、Her-2的表达。结果50例乳腺癌患者中VE     

高脂血症与乳腺癌

<正>近年来随着生活水平和早期诊断水平的提高,乳腺癌发病率呈上升趋势,位居女性恶性肿瘤首位。因此,乳腺癌危险因素受到广泛关注,其中初潮年龄早、绝经年龄晚延长雌激素暴露时间,明确增加了Luminal型乳腺癌的发病风险~([1-2])。血脂代谢是卵巢外雌激素合成的主要途径,因此高脂血症与乳腺癌发病风险的关系引起了广泛关注~([3-4])。早期诊断和治疗水平的提高使乳腺癌人群不     

乳腺癌腋窝淋巴结转移的相关因素分析

目的:探讨乳腺癌患者腋窝淋巴结转移的相关因素。方法:回顾性分析675例乳腺癌患者的病理资料,探讨雌激素受体、孕激素受体、人表皮生长因子受体表达规律并分析其与腋窝淋巴结转移的关系。结果:腋窝淋巴结阳性率43.72%,雌激素受体、孕激素受体、Ki-67蛋白阳性率分别为67.16%,71.12%,91.75%,人表皮生长因子受体过表达率14.19%。雌激素受体、孕激素受体、Ki-67蛋白、人表皮生长因子受体与淋巴结转移无相关性。结论:淋巴结转移与雌激素受体、孕激素受体、Ki-67蛋白、人表皮生长因子受体表达是相对独立、相互补充的乳腺癌预后因素。     

托瑞米芬对乳腺癌术后内分泌系统及子宫内膜的影响分析

选取我院2011年1月~2014年2月收治的68例乳腺癌术后患者。随机分为A组和B组各34例。A组使用托瑞米芬治疗,B组实施他莫昔芬治疗,对两组患者治疗后内分泌系统情况与子宫内膜厚度的影响进行观察。结果两组患者治疗前的血清雌激素水平及血清孕激素水平均无明显差异,经治疗后,两组患者均有改善,但是A组血清孕激素上升水平及血清雌激素下降水平均高于B组(P<0.05)。治疗后,A组子宫内膜厚度无明显差异(P>0.05),B组子宫内膜厚度与治疗前有明显差异(P<0.05)。对乳腺癌术后患者采取托瑞米芬治疗,可提高孕激素水平,降低雌激素水平,未发现子宫内膜厚度增加,子宫内膜病变发生得以控制,值得临床推广。     

理性看待绝经激素治疗与乳腺癌发病风险

随着当代女性对绝经认知的不断提高,越来越多的女性开始进行绝经激素治疗(menopausal hormone therapy,MHT),以缓解绝经相关症状,如月经紊乱、潮热、多汗、睡眠障碍、情绪波动、泌尿生殖道萎缩以及骨质疏松等,进而提高生活质量.但在应用MHT的过程中,乳腺癌的发病风险一直是困扰女性的重要问题之一,而M...     

Hormone replacement therapy and cancers: the biological roles of estrogen and progestin in tumorigenesis are different between the endometrium and breast

Hormone replacement therapy (HRT) has become available over the past few decades, but the risk of breast cancer with HRT remains controversial. The Women's Health Initiative Study has recently demonstrated that women receiving estrogen plus progestin (HRT) have an increased risk of invasive breast carcinoma, although women receiving estrogen alone (estrogen replacement therapy) exhibit no increased risk of breast carcinoma. By contrast, the risk of endometrial carcinoma increases with estrogen replacement therapy, while HRT reduces the risk of endometrial carcinoma. These clinical findings suggest that the biological roles of estrogen and progestin in tumorigenesis are certainly different between the endometrium and breast, although both are considered "estrogen-dependent tissues". In this review, I summarize the recent studies and indicate that the enzymes responsible for intratumoral estrogen metabolism and biosynthesis are markedly different between human breast and endometrial carcinomas. 17beta-hydroxysteroid dehydrogenases (17-HSDs) are enzymes estrogen replacement therapyinvolved in the formation of active sex steroids. Estrogens are interconverted by two enzymes, 17-HSD types 1 and 2. Type 1 converts estrone to estradiol, and type 2 catalyzes the reverse reaction. 17-HSD type 5 reduces androstenedione to testosterone. 17-HSD type 1 plays an important role in the regulation of high estradiol levels in breast carcinoma tissues, whereas 17-HSD types 2 and 5 appear to be essential for the maintenance of estradiol concentrations in endometrial carcinoma tissues. In addition, the biological significance of progesterone receptor isoforms differs between endometrial and breast carcinomas. These findings may provide new insights into the biology of "estrogen-dependent tissues".     

In vivo and in vitro effect of progesterone on the growth of some mouse and human tumours

The effect of progesterone on the growth of tumours of different morphological and cytokinetic characteristics and origin has been investigated, such as mammary aplastic carcinoma, Ehrlich ascitic and solid tumour, fibrosarcoma, melanoma B-16, myeloid leukaemia and three cell lines, HeLa, HEp-2 and L929. The administration of progesterone has been proved to stimulate the growth of aplastic carcinoma of the breast in vivo. Directly implemented into cell culture of the same tumour it increased the incorporation of 3H-thymidine into DNA. In HeLa and HEp-2 cell cultures progesterone stimulated the population growth of these cells. However, progesterone has shown no effect at all on the growth of fibrosarcoma, melanoma, Ehrlich tumour, myeloid leukaemia and L929 cells, fibroblasts of C3H mice.     

Metastatic cancer with unknown primary

Close cooperation between an experienced pathologist and oncologist is essential in the management of patients with unknown primary carcinoma. A comprehensive pathological examination is crucial and, with undifferentiated tumors, this will include immunohistology and/or electron microscopy. Ample properly processed tissue therefore must be provided. Time-consuming and costly radiographic and imaging studies should be avoided. No matter how extensive the evaluation, in a majority of cases, the primary site will never be found, so a selective search for treatable tumors is most appropriate and cost-effective. With adenocarcinomas, this will include prostate, breast, and ovary; for undifferentiated tumors, small cell bronchogenic carcinoma, lymphomas, and germ cell tumors. Table 4 summarizes recommended studies for diagnosing unknown primary undifferentiated or adenocarcinomas. Women with adenocarcinoma in axillary nodes without a primary site should be treated as having breast cancer. Estrogen and progesterone receptor assays are to be obtained on the axillary biopsy. High and midcervical nodes with metastatic squamous cell carcinoma can be treated effectively and, not infrequently, cured with surgery and radiation therapy, even if the primary site never is detected. If doubt remains, treatment should be selected that offers the best chance of significant palliation or cure--for example, cisplatin-based chemotherapy in possible extragonadal germ cell tumors.     

Breast cancer: new technologies for risk assessment and diagnosis.

In the US, one in every eight women will develop breast cancer in her lifetime. Despite the advances made in treating breast cancer, the causal mechanisms underlying this disease have yet to be fully elucidated; 85% of breast cancer cases occur sporadically without any known genetic mutation. Too little is known about the pathogenesis of breast cancer for primary prevention to be feasible in the near- to mid-term. Secondary prevention through screening offers an alternative that has been widely adopted. For decades, breast self-examination has been touted as a technique for the early identification of breast cancer. However, it has been recently suggested that this technique is a waste of time and resources for both doctors and patients. Mammography finds breast cancer earlier than breast self-examination, and will reduce the risk of death from breast cancer by approximately 30% in women over 50 years old. Mammography is limited in that cancer, like breast tissue, appears white on the x-ray; therefore lesions may be difficult to detect in women with very dense breasts, and a tumor may not cast a significant shadow until it is quite large. Some cancers are so aggressive that they can spread quickly, before routine screening can detect them. Despite these limitations, mammography is still viewed as the best tool currently available for screening and early diagnosis. Improved methods to detect and diagnose breast cancer early, when it is most curable, are required if a significant impact on morbidity and mortality from breast cancer is to be made. Various new and innovative technologies are being investigated for improving the early detection and diagnosis of breast cancer. About 85% of breast cancers begin in the milk ductal system of the breast. As cancer develops in the breast, abnormalities occur, including atypical hyperplasia, ductal carcinoma in situ, and invasive breast carcinoma. Thus, the early screening of ductal cells can provide a parallel benefit to the 'Pap' smear, which is used virtually universally to identify the abnormal cells that can lead to cervical cancer. Two technologies to monitor for atypical ductal epithelial cells are Cytyc Corporation's FirstCyte Ductal Lavage system and Nastech Pharmaceutical Company's Mammary Aspiration Cytology Test. Matritech, Inc. is searching for biomarkers linked to breast cancer. Researchers at Matritech have detected the presence of nuclear matrix protein (NMP) in the blood of women at the early stage of breast cancer, which is absent in the blood of healthy women, as well as those with fibroadenoma, a benign breast disease. NMP66 has been selected as a marker for further development and clinical trials of a test for use in the detection and monitoring of women with, or at risk for, breast cancer have been initiated. Technologies developed by the US Department of Defense are under investigation as breast cancer screening. Advanced Image Enhancement, Inc. has licensed naval sonar technology for digital image enhancement of mammograms. New thermography applications are also being investigated in two separate projects sponsored by the US Department of Defense using military thermal surveillance tools adapted for cancer detection. Both are enhancements of older thermal imaging technology based on the principle that heat equates to unwanted activity, in the case of breast cancer, abnormal cell proliferation.     

Glycogen-rich clear cell carcinoma of the breast: a case report

Glycogen-rich clear cell carcinoma (GRCC) of the breast is a rare malignant breast tumor. We recently encountered a case of GRCC and report our imaging findings here. The patient was a 49-year-old woman with a mass in her right breast. Mammographic study showed no definite mass shadow because the breast was dense. No calcifications were identified. Ultrasonography disclosed a hypoechoic mass that had a diameter of 1.3 cm, partially irregular borders, heterogeneous internal echoes, and posterior acoustic enhancement, suggesting an invasive carcinoma. Histologic study of core needle biopsy specimens showed a solid proliferation of large clear carcinoma cells, suggestive of a ductal carcinoma. The carcinoma cells possessed clear cytoplasm larger than that typical of ductal carcinoma cells. Breast-conserving surgery was performed with axillary sentinel lymph node biopsy. Macroscopically, the tumor was a solid, white-yellow mass with fairly well defined margins. Histologic examination of the tumor showed a characteristic feature of GRCC: the tumor cells were positive for estrogen receptor but negative for progesterone receptor and Her 2, and the sentinel lymph node was histologically negative. The patient remains well and has had no clinical recurrence of the disease after 2.5 years of follow-up without radiotherapy or adjuvant therapy. Noteworthy is the usefulness of mammography and ultrasonography, which should be used as complementary imaging tools.     

Indications for hormone replacement therapy

Postmenopausal primary ovarian insufficiency may lead to the clinical picture of the climacteric syndrome and to metabolic changes inducing specific diseases due to oestrogen deficiency. In symptomatic states of oestrogen deficiency, Hormone Replacement Therapy (HRT) is indicated for therapeutic reasons. If there is an increased risk for osteoporosis, for cardiovascular diseases or for Alzheimer's Disease, the preventive administration of HRT has to be discussed. In the combined presence of an increased metabolic risk and of subjective symptoms, HRT is still the best choice. Recent alternatives to classical HRT are Tibolone and, in the later postmenopause, Raloxifene. Incorrect media reports lead to insecurity and to concerns about the use of sexual steroids after menopause. HRT can be accompanied by a small weight increase of 200-500 g. However, more important in most women is the normal trend to weight gain in the 40s and 50s. HRT does not increase blood pressure. If there are some hints for an abnormal coagulation system in the personal or family history of a patient, thrombophilia should be excluded before the begin of HRT. The risk to have an endometrial carcinoma during HRT is not increased, but endometrial cancers are more frequent with unopposed estrogen administration. The incidence of breast cancer increases continuously with ageing. If 1000 women start HRT at the age of 50 and continue for five years, two more cases of breast cancer are diagnosed within the next 20 years. This small increase of morbidity is not accompanied by an increased mortality due to breast cancer: mortality does not change. The data available today show a clear decrease of total mortality up to the age of 75 years in women using oestrogens and speak in favour of HRT. If HRT is used for less than five years, cancer risk is not increased. The gain in Life Quality primes significantly. For the indication of long term HRT, the risks and benefits have to be evaluated individually.