共识与争议:绝经激素治疗与乳腺癌发病风险

绝经激素治疗(menopausal hormone therapy,MHT)是以雌激素补充为核心的治疗,在有子宫的女性治疗中往往需联合雌激素和孕激素。妇科内分泌和乳腺外科专家就围绝经期MHT是否增加乳腺癌风险展开讨论并达成共识:MHT可增加乳腺癌风险,应用时需全面评估风险与收益;MHT存在用药窗口期、用药指征、禁忌证,应用前需告知患者相关风险并取得知情同意。对天然孕激素、替勃龙及单雌激素治疗是否增加乳腺癌发生风险等问题仍存在争议。     

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世纪初美国大型前瞻性随机对照研究“妇女健康倡议(Women's Health Initiative,WHI) ”中期研究报告的发布,对全球MHT的应用产生了巨大震动,该项研究报告了老年女性使用MHT过程中心脑血管疾病事件及乳腺癌的发生风险升高,在2002年之后的18年里,医学界对MHT获益与风险的再评估从未停止过。目前,较为统一的认识是MHT的获益与风险与多种因素相关,包括启用MHT的年龄,绝经年限,性激素的种类、剂量、使用途径、用药时长,女性的基础健康状况,MHT管理是否规范等。本文参考过去10年内全球颁布的各项MHT指南、共识和发表的重要文献,对MHT的获益与风险进行论述。     

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MHT与乳腺癌发病风险的争论亦成为妇科内分泌领域的热点问题。本文基于循证医学证据，阐述如何理性看待二者之间的关系。     

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     

绝经激素治疗与女性恶性肿瘤

医学的快速发展显著提高了恶性肿瘤患者的生存率和生存时间，因此，越来越多的女性恶性肿瘤幸存者将经历自然绝经或由于肿瘤治疗导致的早发性卵巢功能不全(premature ovarian insufficiency，POI)。自然绝经或POI带来的雌激素水平缺乏，可引起潮热、出汗、失眠、泌尿生殖道萎缩等一系列症状，远期负面影响包括心血管疾病、骨质疏松等风险增加，严重影响女性生活质量。因此，绝经激素治疗(menopausal hormone therapy，MHT)在女性恶性肿瘤幸存者中的应用日益受到关注。本文将对MHT与女性恶性肿瘤的关系及恶性肿瘤幸存者应用MHT的利弊进行分析。     

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。     

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。     

FGFR2基因SNP位点rs11200014多态性与中国女性乳腺癌易感性的关系

目的:研究成纤维细胞生长因子受体2(FGFR2)基因单核苷酸多态性(SNP)位点rs11200014多态性与中国女性乳腺癌易感性的关系.方法:抽取321例乳腺癌患者和330例健康对照组外周血,分离淋巴细胞,抽提基因组DNA,采用聚合酶链-连接酶检测反应检测FGFR2基因SNP位点rs11200014多态性,比较基因型分布和乳腺癌发病风险及临床病理特征的关系.计算危险度比值比及95%CI,应用非条件Logistic回归进行分析计算.结果:FGFR2基因SNP位点rs11200014多态性与中国女性乳腺癌发生风险无明显关系,与淋巴结转移、雌激素受体及孕激素受体状态无明显相关.在年龄大于50岁的女性中,rs11200014 CT基因型降低了患乳腺癌的风险.结论:FGFR2基因SNP位点rs11200014多态性与中国女性乳腺癌易感性之间无明显相关性.     

乳腺癌患者年龄、乳腺X线密度与雌、孕激素受体的相关性研究

目的 探讨乳腺癌患者年龄、乳腺X线密度与雌激素受体(ER)和孕激素受体(PR)表达的相关性。方法 回顾性分析经病理确诊的992例乳腺癌免疫组化和术前乳腺X线检查资料。分析不同年龄组乳腺X线密度分布情况, 分析患者年龄、乳腺X线密度与雌激素受体(ER)和孕激素受体(PR)表达的相关性。结果 52.92%(525/992)的患者乳腺呈高密度。在 <35岁、35-39岁、40-44岁、45-49岁、50-54岁、55-59岁、60-64岁、65-69岁和 >69岁患者中, 低乳腺密度和高乳腺密度比例分别为10.26%和89.74%、21.92%和78.08%、22.92%和77.08%、26.18%和73.82%、43.04%和56.96%、65.24%和34.76%、83.76%和16.24%、89.80%和10.20%及94.12%和5.88%, <55岁与≥55岁患者间乳腺X线密度差异有统计学意义(z=-16.11, P <0.01)。乳腺癌患者年龄与ER呈轻微正相关(r=0.09, P <0.01), 与PR呈轻微负相关(r=-0.14, P <0.01);乳腺X线密度与ER呈轻微负相关(r=-0.07, P=0.02), 与PR无明显相关性(r=0.05, P=0.13)。结论 乳腺癌患者年龄和乳腺X线密度与ER和PR表达水平有关, 其对ER和PR的表达情况具有潜在评估作用。     

口服避孕药与乳房肿块的相关性研究

正常见的乳房肿块包括乳腺囊性增生病、乳房纤维瘤、乳管内乳头状瘤、乳腺癌。乳腺囊性增生病与体内雌、孕激素比例失调有关,雌激素是乳房纤维瘤发生的刺激因子,雌酮和雌二醇与乳腺癌的发病有关[1]。本研究探讨口服避孕药与乳房肿块患病风险的相关性,现报告如下。1资料与方法1.1一般资料选取2014年1月—2015年12月本院368例乳房肿块患者(包括既往因乳腺疾病手术的病     

无心脏基础疾病的老年HER-2阳性乳腺癌患者是否应行曲妥珠单克隆抗体治疗?

随着我国人口老龄化,乳腺癌治疗需要面对更多的老年患者。近年来,靶向治疗作为人表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)阳性乳腺癌全身治疗的重要方法,在乳腺癌治疗中的地位越来越重要。无心脏基础疾病的老年HER-2阳性乳腺癌患者是否应使用曲妥珠单克隆抗体进行靶向治疗存在争议。目前证据表明,60~70岁老年HER-2阳性乳腺癌患者可从曲妥珠单克隆抗体治疗中获益,心脏事件风险较低且可逆,但70岁以上患者目前无大规模试验证据支持。在选择辅助治疗方案时需平衡获益与风险,综合考虑患者本人意愿和身体状况,进行个体化治疗。若治疗选择曲妥珠单克隆抗体,需避免与蒽环类化疗药物联用并监测心功能,及时发现和处理心脏事件。     

Breast response to menopausal hormone therapy--aspects on proliferation, apoptosis and mammographic density

Breast cancer is the major malignancy among women in the Western world. The breast is clearly a target organ for sex steroid hormones and hormonal treatments have been associated with an increased risk of breast cancer. The balance between proliferation and apoptosis is important for breast cell homeostasis. Mammographic breast density has been identified as a strong and independent risk factor for breast cancer. It seems clear that there is a difference between various hormonal treatments with regard to their effects on breast density and cell proliferation. Also, not all women respond similarly to the same treatment. Combined estrogen and progestogen therapy generally will enhance density and proliferation more than treatment with estrogen alone. Certain constitutional and hormonal factors appear to be predictive of breast reactivity. Older women with a low body mass index respond more strongly to treatment. Estrogen levels have a positive and androgens a negative association to increase in density and proliferation. A combination of increased proliferation and decreased apoptosis could be one mechanism to explain the excess risk of breast cancer during combined estrogen/progestogen treatment. Tibolone seems to have less impact on breast response than conventional hormone therapy. Efforts should be made to identify those women with an adverse response to treatment as well as therapeutic principles with the least possible influence on the breast.     

Chemoprevention of breast cancer

We critically examined the literature regarding tamoxifen and raloxifene for breast cancer chemoprevention, a controversial topic of interest to all providers of health care services for women. The National Surgical Adjuvant Breast and Bowel Project showed that tamoxifen decreased the incidence of breast cancer in women at increased risk. Two European studies did not confirm this benefit. Although well-tolerated, tamoxifen chemoprevention continues to be associated with an increased risk of endometrial cancer. Raloxifene is a promising agent that has not been established to reduce the incidence of breast cancer in women at increased risk and currently should not be considered an alternative to tamoxifen outside of clinical trials. Tamoxifen results in a decreased risk of causing breast cancer in women at increased risk for having the disease. Women at increased risk are encouraged to participate in the ongoing clinical trial comparing tamoxifen and raloxifene for breast cancer prevention.     

Risk of breast cancer and breast cancer characteristics in women treated with supradiaphragmatic radiation for Hodgkin lymphoma: Mayo Clinic experience

OBJECTIVE: To evaluate the overall risk of breast cancer and breast cancer characteristics in women given supradiaphragmatic radiation therapy for Hodgkin lymphoma. PATIENTS AND METHODS: Medical records of 653 female patients who received supradiaphragmatic radiation therapy for Hodgkin lymphoma at the Mayo Clinic in Rochester, Minn, between 1950 and 1993 were abstracted, and follow-up questionnaires were mailed. In 4 patients, breast cancer was diagnosed before Hodgkin lymphoma was discovered. RESULTS: The median age of 649 patients at supradiaphragmatic radiation therapy was 31.8 years (range, 2.6-86.5 years). The median duration of follow-up was 8.7 years (range, < 1-47.9 years). In 30 patients, breast cancer developed (bilaterally in 4 patients) after supradiaphragmatic radiation therapy; the median interval was 19.9 years (range, 0.7-423 years). The median age at breast cancer diagnosis was 44.4 years (range, 27.5-70.8 years). The standardized morbidity ratio for breast cancer after supradiaphragmatic radiation therapy was 2.9 (95 % confidence interval [CI], 2.0-4.2) (P < .001). Breast cancer risk significantly increased 15 to 30 years after patients received supradiaphragmatic radiation therapy, and risk was inversely related to age at supradiaphragmatic radiation therapy until age 30 years. The standardized morbidity ratio for patients younger than 30 years at supradiaphragmatic radiation was 8.5 (95% CI, 53-13.1) vs 1.2 (95% CI, 0.5-2.2) for those aged 30 years or older (P < .001). Splenectomy increased breast cancer risk (P = .01). Breast cancer detection was by self-examination in 15 cancers, by mammography in 13, and by clinical examination in 4; in 2 cancers, the mode of detection was unknown. Modified radical mastectomy was used to treat breast cancer. CONCLUSION: The increased risk of breast cancer in survivors of Hodgkin lymphoma given supradiaphragmatic radiation therapy appears to be limited to patients who are younger than 30 years at radiation therapy or to those who have undergone splenectomy.     

THE LONG-TERM RISKS AND BENEFITS OF HORMONE REPLACEMENT THERAPY

There is increasing awareness that the long-term consequences of ovarian failure can be prevented or reduced with appropriate hormone replacement therapy (HRT). After the menopause, there is a rapid loss of trabecular bone resulting in a one in two lifetime risk of osteoporotic fracture. HRT prevents this bone loss and decreases the incidence of fracture. A minimum of 5 years treatment is recommended for significant benefit. Epidemiological evidence is accumulating that post-menopausal oestrogen therapy reduces the risk of cardiovascular disease and stroke by between 30 and 70% even in the presence of established risk factors. Given the prevalence of cardiovascular disease, this is likely to be one of the principle benefits of HRT in the next decade. Concerns about the long-term safety of HRT have focused on endometrial and breast cancer. The increase in risk of endometrial cancer associated with oestrogen only therapy is abolished with the sequential addition of a progestogen for 10-12 days each cycle. The possible effect of HRT on breast cancer risk has to be considered against the background of a one in 12 lifetime risk of developing this disease. The epidemiological studies investigating this relationship are reviewed in this paper. There is a broad consensus that 5-6 years duration of HRT does not increase breast cancer risk. Longer durations of therapy (10-15 years) have been reported to increase this risk although not all the data are in agreement. Other factors, such as family history and benign breast disease, may also influence the risk of breast cancer. The potential benefits of HRT on mortality and morbidity are enormous. Against this is a possible small increase in breast cancer risk with long-term usage. Greater awareness of the long term consequences of the menopause and the potential benefits of HRT should be encouraged so that women can make informed decisions about their need for HRT.     

20. Oral contraceptives,hormone replacement therapy and breast cancer

Both oral contraceptives (OCs) and hormone replacement therapy (HRT) are widely used by healthy women, so that any increase in breast cancer has to be considered in relation to the avoidance of either pregnancy or menopausal symptoms. Use of OCs for more than four years before first full term pregnancy leads to a small but significant increase in risk of breast cancer (6.5 extra cases per 10,000 women aged 20-29) that persists for 10 years after cessation. Risk is not amplified by a positive family history and OC-induced breast cancers are more likely to be localised to the breast. For those taking HRT there is an increased relative risk of breast cancer of 2.3% per year, similar to the increase in risk for each extra year spent in a premenopausal state. The increase in risk disappears five years after cessation. HRT does not lead to any increase in risk of dying of breast cancer. Some breast cancer patients can safely take HRT, and it is possible that some formulations may reduce the subsequent risk of relapse.