Project Details
Description
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.
Status | Finished |
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Effective start/end date | 1/1/20 → 12/31/23 |
Funding
- National Cancer Institute: $890,696.00
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