Exposure to high dose estrogens in adolescence: long term effects on mammographic breast density

乳腺密度是乳腺癌的一个公认的危险因素，并且已被证明在成年生活中受到激素暴露的可逆影响。由于青春期性激素的重要作用之一是乳腺细胞增殖，因此在生命早期阶段接触性激素可能会对乳腺组织的组成和密度以及随后的乳腺癌风险产生持续影响。该项目旨在通过验证青春期暴露于大剂量性激素对乳房x线摄影密度有长期影响的假设，提高我们对青春期性激素对乳腺癌风险影响的理解。这将通过比较在青春期接受高剂量雌激素治疗的高身材女性和同样接受高身材评估但未接受治疗的女性的乳房x线摄影密度来完成。在此之前的人类研究中，没有研究过在生命早期暴露于高剂量雌激素对乳房组织的长期影响。这并不奇怪，因为很难找到合适的暴露人群。这组女性，根据身高进行评估或治疗，为我们提供了一个独特的机会来研究这些影响。这项研究将增加我们对青春期性激素对乳房x线摄影密度和乳腺癌风险的影响的理解。如果青春期的荷尔蒙因素被证明会影响乳房x线摄影密度，这可能会为乳腺癌预防工作带来新的途径，这些工作的目标是在生命的早期。这一信息可能导致新的研究方向，检查青少年激素暴露（内源性和外源性）及其对乳腺组织的影响。

Breast density is a well established risk factor for breast cancer, and has been shown to be reversibly influenced by hormone exposures in adult life. As one of the important roles of sex hormones during puberty is mammary cell proliferation, it is plausible that exposures at this earlier life stage might have a sustained influence on breast tissue composition and density, and subsequent breast cancer risk. This project aims to increase our understanding of the influence of sex hormones in adolescence on breast cancer risk by testing the hypothesis that exposure to large doses of sex hormones during adolescence has long-term effects on mammographic density. This will be done by comparing the mammographic densities of women who were treated with high doses of estrogen for tall stature during adolescence with women who were similarly assessed for tall stature but not treated. No previous study in humans has examined the long-term effects on breast tissue of high dose estrogen exposure at this early life stage. This is not surprising, given the difficulty in finding a suitable exposed population. This cohort of women, assessed or treated for tall stature, provides us with a unique opportunity to examine these influences. This research will add to our understanding of the influence of sex hormones in adolescence on mammographic density and breast cancer risk. If hormonal factors in adolescence are shown to influence mammographic density, this may lead to new avenues for breast cancer prevention efforts that are targeted much earlier in life. This information may lead to new research directions examining adolescent hormonal exposures (both endogenous and exogenous) and their influence on breast tissue.