Sex hormones and breast cancer risk and prognosis
Sex hormones and breast cancer risk and prognosis
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DOI：
10.1016/j.breast.2013.07.007
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发表时间：
2013-08-01
期刊：
影响因子：
3.9
通讯作者：
Dowsett, Mitch
中科院分区：
文献类型：
--
作者：
Folkerd, Elizabeth;Dowsett, Mitch
对乳腺癌发病前妇女的大量前瞻性血浆样本进行的研究已经确定，某些性类固醇与乳腺癌风险显著相关。在绝经后的妇女中发现了最强烈的联系她们体内大多数激素的变异性明显减少但在绝经前的妇女中也发现了一些积极的联系。血浆雌激素显示出与风险的最强相关性，通过测量或计算不含性激素结合球蛋白（SHBG）的雌二醇的比例，这种相关性得到了加强，这与雌二醇是最活跃的部分相一致。据报道，这种关系几乎可以解释绝经后妇女的乳腺癌与体重指数之间的所有联系；这可能是由于皮下脂肪中非卵巢雌激素的合成是突出的。这些密切的关系导致血浆和尿液雌激素水平被用作中间终点，以寻找通过类固醇处置作用影响乳腺癌风险的基因。血浆雄激素水平也显示出与乳腺癌风险的关系，这种关系被“纠正”雌激素水平削弱了，但没有消除。这被认为是局部产生雌激素在乳腺癌病因学中很重要的证据。鉴于血浆类固醇水平与乳房x线摄影密度不密切相关，而乳房x线摄影密度与风险密切相关，因此存在将这两个因素结合起来评估乳腺癌风险的机会，但合适的雌激素检测方法的低可用性是主要障碍。在确定的乳腺癌中，血浆雌激素已被发现与雌激素依赖基因的基因表达相关，并且这些基因的表达在绝经前妇女的月经周期中有所不同。很少需要常规测量血浆雌激素水平，但它在芳香化酶抑制剂的比较药理学和剂量相关有效性中很重要。可能需要测量来确定在细胞毒性化疗后闭经的妇女的卵巢功能残留，这表明她们不适合芳香酶抑制剂治疗。使用高灵敏度的检测也显示，在服用第三代芳香化酶抑制剂的患者中，BMI和血浆雌激素水平之间的关联持续存在，而一些阴道雌激素制剂的血浆雌激素水平出现可测量的增加，这与治疗效果有关。(C) 2013 Elsevier Ltd.版权所有。
The study of large prospective collections of plasma samples from women prior to the development of breast cancer has firmly established certain sex steroids as being significantly associated with risk. The strongest associations have been found in postmenopausal women in whom the within person variability of most hormones is markedly reduced but some positive associations have also been seen in premenopausal women. Plasma estrogens show the strongest correlations with risk and these are strengthened by measurement or calculation of the proportion of estradiol that circulates free of sex hormone binding globulin (SHBG), consistent with this being the most active fraction. The relationships have been reported to potentially explain virtually all of the association of breast cancer with body mass index in postmenopausal women; this is likely to be due to non-ovarian estrogen synthesis being prominent in subcutaneous fat. These strong relationships have led to plasma and urine estrogen levels being used as intermediate end-points in the search for genes that affect breast cancer risk via their role in steroid disposition. Plasma androgen levels also show a relationship with breast cancer risk that is weakened but not eliminated by 'correction' for estrogen levels. This has been argued to be evidence of the local production of estrogens being important in the etiology of breast cancer. Given that plasma steroid levels do not correlate closely with mammographic density, which is strongly associated with risk, the opportunity exists to combine the two factors in assessing breast cancer risk but the low availability of suitable estrogen assays is a major impediment to this. In established breast cancer, plasma estrogens have been found to correlate with gene expression of estrogen dependent genes and the expression of these varies across the menstrual cycle of premenopausal women.There is infrequently a need for routine measurement of plasma estrogen levels but it has been important in the comparative pharmacology and dose-related effectiveness of aromatase inhibitors. Measurement may be needed to identify residual ovarian function in women who have amenorrhea subsequent to cytotoxic chemotherapy indicating their unsuitability for aromatase inhibitor treatment. Use of highly sensitive assays has also revealed that the association between BMI and plasma estrogen levels persists in patients on 3rd generation aromatase inhibitors and that measurable increments in plasma estrogen levels occur with some vaginal estrogen preparations that are of concern in relation to treatment efficacy. (C) 2013 Elsevier Ltd. All rights reserved.