The Academic Department of Biochemistry, The Royal Marsden NHS Foundation Trust, Wallace Wing, Fulham Road, London SW3 6JJ, UK.
Breast. 2013 Aug;22 Suppl 2:S38-43. doi: 10.1016/j.breast.2013.07.007.
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.
在乳腺癌发生之前，对大量前瞻性血浆样本的研究已经确定了某些性激素与风险显著相关。在绝经后妇女中发现了最强的相关性，在这些妇女中，大多数激素的个体内变异性明显降低，但在绝经前妇女中也发现了一些阳性相关性。血浆雌激素与风险的相关性最强，通过测量或计算循环中游离性激素结合球蛋白（SHBG）的雌二醇比例，这种相关性得到了加强，这与最活跃的部分一致。这些关系据报道可以解释绝经后妇女中乳腺癌与体重指数之间几乎所有的关联；这可能是由于非卵巢雌激素合成在皮下脂肪中更为突出。这些强烈的相关性导致血浆和尿液雌激素水平被用作寻找通过其在类固醇处置中的作用影响乳腺癌风险的基因的中间终点。血浆雄激素水平与乳腺癌风险也存在相关性，但通过“校正”雌激素水平，这种相关性减弱但并未消除。这被认为是局部产生雌激素在乳腺癌发病机制中重要的证据。鉴于血浆类固醇水平与强烈相关的乳腺癌风险的乳腺 X 线密度相关性不密切，因此有机会将这两个因素结合起来评估乳腺癌风险，但缺乏合适的雌激素检测方法是一个主要障碍。在已确诊的乳腺癌中，发现血浆雌激素与雌激素依赖性基因的基因表达相关，这些基因的表达在绝经前妇女的月经周期中发生变化。通常不需要常规测量血浆雌激素水平，但在芳香酶抑制剂的比较药理学和剂量相关疗效中非常重要。在接受细胞毒性化疗后出现闭经的妇女中，可能需要测量以确定其卵巢功能是否残留，这表明她们不适合接受芳香酶抑制剂治疗。使用高灵敏度的检测方法还揭示，BMI 与血浆雌激素水平之间的关联在使用第三代芳香酶抑制剂的患者中仍然存在，并且一些阴道雌激素制剂会导致血浆雌激素水平可测量增加，这与治疗效果有关。
