Biomarker Breast Pap Test

描述（由申请人提供）：本I期研究计划旨在研究开发一种新型生物标志物乳腺PapTest的可行性，用于筛查乳头抽吸液（NAF），并在乳房x光检查可检测的肿瘤发展之前在肿瘤形成阶段检测乳腺癌。尽管近年来乳腺癌的死亡率略有下降，但它仍然是美国妇女癌症诊断最多的癌症，也是癌症死亡的第二大原因。如果在肿瘤形成之前就发现高危妇女并进行预防性治疗，我们可以预期发病率和死亡率将大幅下降。然而，准确识别高危妇女采取预防措施一直是一项重大的临床挑战。目前，通过Gail评分和使用neommatrix仪器（HALO乳腺巴氏试验）对NAF引起的导管细胞进行细胞学检查来评估风险。然而，许多研究表明，基于细胞学的风险评估是高度主观的，不够精确，无法进行预防性治疗。在NAF细胞中研究了一些任意选择的标记物作为风险预测因子，但到目前为止还没有确定。我们的长期目标是在没有可检测到的肿瘤的情况下，通过识别高风险妇女来降低乳腺癌的发病率。在I期，我们计划研究几个标记物，用于测试开发，这些标记物先前被证明可以准确预测癌前肿瘤患者的风险。我们的目标包括通过筛选癌症、ADH、良性肿瘤和健康受试者的NAF来识别潜在的标志物。在II期，我们的目标包括筛选大量NAF样本，将多种标记物的表达与肿瘤发展联系起来，建立和验证多标记物测试算法。这项工作具有创新性，因为风险评估将基于NAF中多种促癌分子的表达，并利用我们之前在癌前患者中建立的风险预测标记。我们期望NAF中癌症标志物的表达能够在没有检测到肿瘤的情况下，准确预测任何女性的乳腺癌风险，而不考虑细胞学、家族史或任何其他传统风险因素。这项研究的结果意义重大，因为一旦这项测试得到开发和验证，它就可以用于筛查任何没有乳房x光检查或核磁共振检查可检测到的肿瘤的女性，并准确预测乳腺癌的风险。这一结果将是乳腺癌分子风险预测的重大突破。肿瘤形成前的治疗和预防将成为现实。我们预计，研究结果将对大幅降低乳腺癌发病率和死亡率产生重大影响，同时节省数十亿美元的医疗保健费用。

DESCRIPTION (provided by applicant): This Phase I research proposal is to investigate the feasibility of developing a novel Biomarker Breast PapTest for screening Nipple Aspirate Fluid (NAF) and detecting breast cancers at the tumor-in-formation stage before mammographically detectable tumors are developed. Although there is a slight decline in deaths from breast cancer in recent years, it continues to be the most diagnosed cancer and the second leading cause of cancer deaths for women in the USA. We can expect a drastic reduction in the incidence and deaths if high risk women are identified before tumor formation and treated prophylactically. However, precise identification of high risk women for prophylactic measures has been a major clinical challenge. Currently, risk is assessed by Gail scoring and cytological examination of ductal cells in NAF elicited using NeOMatrix instrument (HALO Breast Pap Test). However, numerous studies have shown that cytology based risk assessment is highly subjective and not precise enough to undertake prophylactic treatments. Several arbitrarily selected markers were explored in NAF cells as risk predictors, but none established thus far. Our long range goal is to reduce breast cancer incidence by identifying high risk women in the absence of detectable tumors. In Phase I we plan to investigate several markers for test development that were previously shown to accurately predict risk in patients with premalignant tumors. Our aims include identifying potential markers by screening NAF from subjects with cancer, ADH, Benign tumors and healthy subjects. In Phase II our aims include screening large number of NAF samples and correlating the expression of multiple markers with tumor development, multimarker Test algorithm building and validation. The proposed work is innovative, because risk assessment will be based on the expression of multiple cancer promoting molecules in NAF and capitalizes on our previously established risk prediction markers in premalignant patients. It is our expectation that expression of cancer markers in NAF will precisely predict breast cancer risk in any woman irrespective of cytology, family history or any other conventional risk factors in the absence of detectable tumors. The outcomes will be significant because once the test is developed and validated it could be applied to screen any women in the absence of mammographically or MRI detectable tumors and precisely predict breast cancer risk. The outcomes will be a major break-though in molecular risk prediction for breast cancer. Treatment before tumor formation and prevention will become a reality. It is our expectation that the outcomes will have a major impact in drastically reducing the incidence and deaths from breast cancer, simultaneously saving Billions of dollars in Health Care Cost.