Epidemiology of MRI parenchymal enhancement: A new marker of breast cancer risk

描述（由申请人提供）：在乳腺MRI筛查期间，给予造影剂以帮助肿瘤可视化，从而增强（变得更亮）。正常乳腺组织在MRI上也会增强（称为背景实质增强[BPE]），我们已经证明，这种正常组织增强的程度与乳腺癌风险密切相关。目前尚不清楚为什么会出现这种情况，也不知道这种增强所代表的生物学基础。本研究的目的是确定已知的乳腺癌危险因素和BPE之间的关系，并开发和验证一种计算机辅助的定量方法来测量BPE。据推测，BPE可能代表乳腺组织对女性激素水平的反应，使其成为乳腺癌风险的良好指标。这将是迄今为止在任何女性群体中进行的最大规模的BPE测量研究，也是第一个解决定量测量方法需求的研究。将提出三个具体目标来检验我们的主要假设并提出本申请的总体目标：1）使用在纪念斯隆-凯特琳癌症中心（MSKCC）可获得的用于分析乳腺MRI的软件开发和验证BPE的客观定量测量，2）探索健康高危绝经前和绝经后妇女中MRI上的BPE与已知乳腺癌风险因素之间的关系，以及3）确定健康高危绝经后妇女MRI检查时血清激素水平与BPE程度之间的关系。这项研究的结果将提供有关BPE（一种新的乳腺癌风险高度预测指标）与已知乳腺癌风险因素（包括循环激素水平）之间关系的关键信息。此外，这里开发的定量方法将产生一个连续的测量BPE，一个预计将提供一个更准确的图片BPE和乳腺癌风险之间的关系比放射科医生使用的四点分类量表。这将有助于更好地对已经是高风险的妇女进行分类（即，有乳腺癌家族史或个人史者）。这项拟议的研究意义重大，因为它将开始表征这种新的风险标志物，为未来探索BPE与乳腺癌风险之间关系的研究提供必要的基础。 公共卫生相关性：拟议的项目与公共卫生有关，因为它试图描述一种新的乳腺癌风险标志物，这种标志物有可能大大提高接受乳腺MRI筛查的高危妇女乳腺癌风险预测的准确性。这将有助于指导有关后续行动的决定，包括预防性护理。在未来，它也可能被证明是有用的，作为一个非侵入性的标志物的反应，化学预防措施和治疗，允许个性化的适应治疗方案在真实的时间，并制定真正个性化的治疗方案。

DESCRIPTION (provided by applicant): During breast MRI screening a contrast agent is administered to aid in the visualization of tumors, which enhances (becomes brighter). Normal breast tissue also enhances on MRI (termed background parenchymal enhancement [BPE]) and we have shown that the degree to which this normal tissue enhances is strongly associated with breast cancer risk. It is not clear why this would be the case and the biological underpinnings of what this enhancement represents are not known. The objective of the current study is to determine the relationship between known breast cancer risk factors and BPE and to develop and validate a computer-assisted quantitative approach to the measurement of BPE. It is hypothesized that BPE may represent the breast tissue response to the hormonal profile of a woman, making it a good indicator of breast cancer risk. This will be the largest study of BPE measurements in any group of women to date and the first to address the need for a quantitative method of measurement. Three specific aims will be addressed to test our primary hypothesis and to address the overall objective of this application: 1) Develop and validate an objective quantitative measure of BPE using software for analyzing breast MRIs available at Memorial Sloan-Kettering Cancer Center (MSKCC), 2) Explore the relationship between BPE on MRI and known breast cancer risk factors in healthy high-risk pre- and post-menopausal women and 3) Determine the relationship between serum hormone levels at the time of MRI and degree of BPE in healthy high-risk postmenopausal women. The results of this study will provide crucial information regarding the relationship between BPE, a new highly predictive indicator of breast cancer risk, and known breast cancer risk factors including circulating levels of hormones. Additionally, the quantitative method developed here will yield a continuous measure of BPE, one that is expected to provide a more accurate picture of the relationship between BPE and breast cancer risk than the four-point categorical scale used by radiologists. This will allow for better classification of already high-risk women (i.e., those with a family or personal history of breast cancer). The proposed research is significant because it will begin to characterize this novel marker of risk, providing the foundation necessary for future studies exploring the relationship between BPE and breast cancer risk. PUBLIC HEALTH RELEVANCE: The proposed project has relevance to public health in that it seeks to characterize a new marker of breast cancer risk that has the potential to greatly improve the accuracy of breast cancer risk prediction in high-risk women undergoing breast MRI screening. This will help to guide decisions regarding subsequent follow-up, including preventative care. In the future, it may also prove to be useful as a non-invasive marker of response to chemoprevention measures and treatment, allowing for individualized adaptation of treatment regimens in real- time, and the development of truly personalized treatment protocols.