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Biomarkers to Improve Targeting of Breast Cancer Prevention in Women with Atypical Hyperplasia

生物标志物可提高非典型增生女性乳腺癌预防的针对性

基本信息

批准号：
9884497
负责人：
Amy C Degnim
金额：
$ 88.45万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9884497
关键词：
Address African American Atypical Hyperplasia of the Breast Atypical hyperplasia Benign Biological Biological Markers Biopsy Breast Breast Cancer Prevention Breast Cancer Prevention Trial Breast Cancer Risk Factor Breast Carcinogenesis Breast Diseases Breast biopsy Clinic Clinical Clinical Trials Computing Methodologies Diagnosis Effectiveness Event Formulation Gel Gene Expression Profiling Goals High Risk Woman Histologic Hormonal Incidence Individual Link Mammary Gland Parenchyma Mammographic Density Measures Methods Molecular Oral Prevention Prevention approach Prevention strategy Prevention therapy Prevention trial RNA Randomized Clinical Trials Research Resources Retrospective cohort Risk Risk Reduction Sampling Sampling Studies Tamoxifen Tissues Toxic effect Transcript Universities Woman Work base biomarker discovery biomarker evaluation breast imaging breast lesion cancer prevention cohort early detection biomarkers experience genetic signature high risk hormone therapy improved individual response individualized prevention innovation insight malignant breast neoplasm nano-string non-invasive imaging novel novel marker personalized decision personalized risk prediction predicting response predictive marker primary endpoint randomized placebo controlled study response response biomarker risk prediction model side effect tool translational study treatment duration uptake

项目摘要

ABSTRACT Approximately 100,000 women per year are diagnosed with atypical hyperplasia (AH) of the breast, a benign breast lesion that is associated with a fourfold increase in risk of subsequent breast cancer. Usage of tamoxifen as cancer prevention therapy following AH diagnosis has been linked to a greater than 50% reduction in subsequent breast cancer incidence. However, uptake of tamoxifen and similar prevention therapies remains low, due in part to a lack of methods to accurately determine which women are at greatest risk for breast cancer (BC), and which women will have a beneficial response to prevention therapy. We propose a highly translational project to address these critical barriers. We will accomplish this by identifying molecular features in benign breast tissue that will 1) improve individualized BC risk prediction for women with AH, 2) serve as biomarkers associated with beneficial response to prevention therapy, and 3) permit assessment of individualized response to prevention therapy, even after a short period of treatment. In Specific Aim 1, we will develop a breast cancer risk prediction model for women with AH that incorporates a NanoString-based gene expression assay in combination with clinical and histological variables; in Specific Aim 2, we will utilize a newly developed benign breast tissue cohort to identify biomarkers that predict beneficial response to tamoxifen; in Specific Aim 3, we will conduct a randomized clinical trial of tamoxifen versus a novel tamoxifen metabolite with less toxicity. This trial in women with AH will determine if beneficial biomarker responses to tamoxifen are observed after only four weeks of treatment. Together, our proposed studies will develop biomarkers that will have immediate relevance to women with AH, and implementation of these approaches in the clinic will have a powerful and sustained impact on the field of BC prevention.

摘要