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张敬杰教授:绝经后激素受体阳性乳腺癌患者心血管风险的有效管理

2017-10-23 佚名 肿瘤资讯

乳腺癌居全球女性恶性肿瘤发病率之首,我国女性多在45~55岁之间自然绝经,45岁以上乳腺癌在我国占所有乳腺癌的三分之二。因此,国内超过半数的乳腺癌患者在发病时已处于围绝经期或绝经期。

乳腺癌居全球女性恶性肿瘤发病率之首,我国女性多在45~55岁之间自然绝经,45岁以上乳腺癌在我国占所有乳腺癌的三分之二。因此,国内超过半数的乳腺癌患者在发病时已处于围绝经期或绝经期。

绝经前雌激素对心脏有保护作用,可增加心肌收缩力,增加搏出量,扩张血管,降低外周血管阻力,增加血高密度脂蛋白胆固醇,降低血低密度脂蛋白胆固醇和总胆固醇水平。雌激素作用于血管壁,可抑制动脉粥样硬化斑块的形成,防止动脉硬化,减少50%的冠心病发生,此外还减少心肌梗死和心律不齐症状的发生。绝经前女性与同年龄组的男性相比,冠状动脉粥样硬化性心脏病的发生率与死亡率均明显低于男性。而女性在绝经以后,雌激素水平显着降低,冠心病的发生率迅速上升,60岁以后接近同年龄组男性水平。因此,绝经是心血管疾病发病率和死亡率上升的独立危险因素。

绝经后激素受体阳性乳腺癌患者的雌激素水平同时受到卵巢功能减退和药物治疗的双重影响而进一步下降,在此背景下,除乳腺癌死亡事件外,心血管疾病相关死亡跃居该类患者除乳腺癌死亡事件外的首位。因此,临床医师需要重视绝经后激素受体阳性乳腺癌患者的血脂异常和心血管疾病风险,对绝经后激素受体阳性乳腺癌患者血脂异常进行管理,有效降低绝经乳腺癌患者动脉粥样硬化性心血管疾病(athero sclerotic cardio vascular disease, ASCVD)的风险,进一步改善乳腺癌患者的长期生存状况。

芳香化酶抑制剂是绝经后激素受体阳性乳腺癌患者治疗方案的重要组成部分,可使绝经后激素受体阳性乳腺癌患者体内雌激素降低90%以上,从而达到控制乳腺癌细胞生长、治疗肿瘤的目的。第三代芳香化酶抑制剂已成为早期绝经后雌激素受体阳性乳腺癌患者的首选辅助治疗药物。因为分子结构的不同,不同的芳香化酶抑制剂对绝经后激素受体阳性乳腺癌患者血脂的影响也有所差异。研究表明应用阿那曲唑的心血管风险低于来曲唑和依西美坦,一项荟萃分析结果显示:总体及严重心血管风险的大小排序:来曲唑>依西美坦>阿那曲唑。绝经后患者体内雌激素基本降低到极低水平,这样的雌激素水平对患者的心血管的保护作用已基本丧失,因此建议绝经后激素受体阳性乳腺癌患者通过改善生活方式及使用调脂药物来预防心血管风险。

生活方式改变 调整饮食结构

不要暴饮暴食,以免发生急性胃扩张、消化不良。多吃防癌、抗癌的食物,如新鲜蔬果、菠菜、番茄、芹菜、苹果、枣子、柑橘、菠萝、豌豆、豆芽菜、胡萝卜等;适当地进食些肉、鱼和蛋类,不仅无损,反而有益;油腻或油炸的食物不容易消化,多吃还会使摄入的脂肪过多,应加以节制。戒烟:世界前八位致死疾病中有六种疾病(缺血性心脏病、脑血管病、下呼吸道感染、慢性阻塞性肺疾病、结核和肺癌)与吸烟有关。二手烟暴露可使成人和儿童患多种疾病。二手烟暴露可增加成人患肺癌、心血管疾病和慢性阻塞性肺病的风险,增加哮喘的发病风险,损害肺功能。因此应该不吸烟、避免吸二手烟。戒烟可以通过药物进行,目前我国已被批准使用的戒烟药物有:处方药:伐尼克兰(酒石酸伐尼克兰片)、盐酸安非他酮;非处方药:尼古丁贴片、尼古丁咀嚼胶。每周坚持150分钟以上中等强度的有氧运动,如慢跑、骑车、游泳、跳舞等。需减重的女性,建议每天进行60~90分钟中等强度的运动。保持理想体重或减重:健康体重是指长期保持体重良好的健康状态。目前常用的判断健康体重的指标是体质指数(body mass index,BMI)。BMI应在18.5~23.9kg/m之间。通过运动、控制饮食及行为训练维持或减轻体重,保持体重指数≥20kg/m2且≤24kg/m2,腰围<85cm。定期检测血脂,如果血脂持续升高可选用降脂药物降低血脂。

降脂药物的应用

临床上应用的降脂药物主要有两类,即HMG-CoA还原酶抑制剂("他汀")类与贝丁酸("贝特")类。他汀类主要降LDL-C,贝特类升高HDL-C和降TG作用优于他汀类。降脂干预的首要目标是将LDL-C降至设定的目标水平或更低。因LDL-C未达标而需用降脂药物时,首选他汀类药物。若LDL-C已在目标水平以下,HDL-C水平降低时,则应选用吉非罗齐等贝特类药物。对于"混合型"血脂异常,使用"他汀"未达到降脂目标时,可联合使用合理剂量的他汀与贝特类药物。既往Meta分析显示,乳腺癌患者长期使用他汀类药物,对肿瘤复发风险无影响。药代动力学研究未发现他汀类药物和芳香化酶抑制剂之间存在药物的相互作用,因此对于存在血脂异常的绝经后激素受体阳性乳腺癌患者,可以选择使用他汀类药物降低升高的LDL-C水平,他汀类药物对芳香化酶抑制剂治疗无影响。拒绝接受芳香化酶抑制剂治疗或不能耐受芳香化酶抑制剂的绝经后激素受体阳性乳腺癌患者,可以服用他莫昔芬。



张敬杰教授
北京大学医学部临床肿瘤学院乳腺肿瘤专业博士
中华医学会安徽省分会乳腺病学组常务委员
安徽省医学会乳腺病学专业委员会常委
安徽医科大学第一附属医院乳腺外科副主任
参与研究课题“DIEP在乳腺癌手术中即刻乳房再造的临床应用研究”项目获安徽省科学技术进步一等奖

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    2017-10-25 zxxiang

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目前的前列腺癌治疗方法聚焦在针对雄性激素受体(AR)信号上。然而,雄性激素受体在细胞腔上皮分化中是一个关键的因子,并且在肿瘤抑制方面具有一定的角色作用。因此,雄性激素受体的抑制也许可以激活致瘤信号通路,从而导致转移性去势难治性前列腺癌(CRPC)。最近,有研究人员报道了一个新的肿瘤促进因子ZBTB46,它可以由AR信号通过微RNA(miR)-1的下调从而进行负调控。ZBTB46与恶性前列腺癌相关并

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