Understanding intramammary estrogen homeostasis constitutes the basis of understanding the role of lifestyle factors in breast cancer etiology. Thus, the aim of the present study was to identify variables influencing levels of the estrogens present in normal breast glandular and adipose tissues (GLT and ADT, i.e., 17β-estradiol, estrone, estrone-3-sulfate, and 2-methoxy-estrone) by multiple linear regression models. Explanatory variables (exVARs) considered were (a) levels of metabolic precursors as well as levels of transcripts encoding proteins involved in estrogen (biotrans)formation, (b) data on breast cancer risk factors (i.e., body mass index, BMI, intake of estrogen-active drugs, and smoking) collected by questionnaire, and (c) tissue characteristics (i.e., mass percentage of oil, oil%, and lobule type of the GLT). Levels of estrogens in GLT and ADT were influenced by both extramammary production (menopausal status, intake of estrogen-active drugs, and BMI) thus showing that variables known to affect levels of circulating estrogens influence estrogen levels in breast tissues as well for the first time. Moreover, intratissue (biotrans)formation (by aromatase, hydroxysteroid-17beta-dehydrogenase 2, and beta-glucuronidase) influenced intratissue estrogen levels, as well. Distinct differences were observed between the exVARs exhibiting significant influence on (a) levels of specific estrogens and (b) the same dependent variables in GLT and ADT. Since oil% and lobule type of GLT influenced levels of some estrogens, these variables may be included in tissue characterization to prevent sample bias. In conclusion, evidence for the intracrine activity of the human breast supports biotransformation-based strategies for breast cancer prevention. The susceptibility of estrogen homeostasis to systemic and tissue-specific modulation renders both beneficial and adverse effects of further variables associated with lifestyle and the environment possible.

了解乳房内雌激素稳态是了解生活方式因素在乳腺癌病因中作用的基础。因此，本研究的目的是确定影响正常乳腺和脂肪组织（GLT和ADT）中存在的雌激素水平的变量，即17β-雌二醇，雌酮，3-硫酸雌酮和2-甲氧基-雌酮）的线性回归模型。考虑的解释变量（exVAR）是（a）代谢前体的水平以及编码参与雌激素（biotrans）形成的蛋白质的转录物的水平，（b）乳腺癌危险因素的数据（即体重指数，BMI，摄入量通过问卷收集的雌激素活性药物和吸烟，以及（c）组织特征（即GLT的油的质量百分比，油的百分比和小叶类型）。GLT和ADT中的雌激素水平受乳房外生产（绝经状态，雌激素活性药物和BMI的摄入）的影响，因此表明已知影响循环雌激素水平的变量也首次影响了乳腺组织中的雌激素水平。 。此外，组织内（生物转化）的形成（通过芳香化酶，羟类固醇-17β-脱氢酶2和β-葡萄糖醛酸苷酶）也影响组织内雌激素水平。在对（a）特定雌激素水平和（b）GLT和ADT中相同的因变量表现出显着影响的exVAR之间观察到明显差异。由于GLT的油含量和小叶类型会影响某些雌激素的水平，因此这些变量可包括在组织表征中，以防止样品偏倚。结论，人类乳房内分泌活动的证据支持基于生物转化的乳腺癌预防策略。雌激素稳态对全身和组织特异性调节的敏感性使得与生活方式和环境有关的其他变量的有利和不利影响成为可能。