Identifying Determinants of Indolent versus Aggressive Intraepithelial Neoplasias of the Breast
Abstract
Background: The detection of early-stage abnormal growths (lesions) in the breast has risen dramatically due to widespread mammography. Early detection represents a significant opportunity to intervene and halt the progression of these early lesions to invasive breast cancer. Unfortunately, our limited knowledge of the biology of early-stage breast cancer has prevented us from taking full advantage of early detection. For example, a significant number of women who undergo treatment to "eliminate" their early breast lesions nevertheless develop invasive breast cancer. We do not understand how these lesions progress nor can we identify which lesions will behave aggressively and progress to invasive cancer. Overarching Challenges: In response to these key issues facing breast cancer patients, we will address the following overarching challenges: We will (1) distinguish deadly from indolent breast cancers and (2) identify determinants of breast cancer risk and progression. To achieve these goals, we will use a combination of mouse models and patient samples that display breast lesions at different points in progression (from early stages to more aggressive stages). We will closely examine the appearance of these lesions to see how the lesions change in appearance as they become more aggressive. We will check the ability of these lesions to form new growths in an otherwise-healthy mouse and measure the invasiveness/aggressiveness these new growths. Finally, we will identify the causes of aggressive behavior of breast lesions. Advancement in Research: The molecular biology of early-stage breast lesions remains elusive, due partly to the difficulty in obtaining patient samples and in generating representative mouse models. Our studies will lead to detailed, comprehensive insight into the biology of early-stage breast lesions and, importantly, help us understand why lesions behave aggressively. Specifically, our studies will show how the appearance of a lesion is linked to its aggressiveness and reveal what is driving this aggressive behavior. Applicability and Clinical Impact: By understanding how early-stage breast lesions behave, we will be better able to stratify early-stage breast lesions as benign or aggressive. In addition, our studies will propel us toward identifying effective therapies to halt the advancement or recurrence of breast lesions. Ultimately, we will be able to identify patients most at risk for recurrence of their breast lesion and treat and eliminate these aggressive lesions before they can advance to deadly disease. Additionally, if we can identify with a high degree of accuracy which lesions actually do not progress to breast cancer, we can reclassify these lesions as non-cancerous and spare patients an unnecessary diagnosis of cancer, as well as the significant emotional and psychological burden associated with such a diagnosis. Pathway to a Patient-Related Outcome: Following the studies we have proposed, there remain several follow-up studies to translate our findings to patients at risk for invasive breast cancer. First, we will conduct preclinical animal studies to test potential therapies that are effective at killing breast growths and preventing their recurrence. After identifying the most effective drugs in animals, we will then commence Phase I to III clinical trials to ensure that these drugs are both safe and effective in patients. I expect to undertake these studies over the course of several years as I transition from a postdoctoral fellow to an independent investigator. I will work closely with several expert teams at MD Anderson and the Texas Medical Center, such as the Center for Co-Clinical Trials, the Center for Clinical and Translational Sciences, and the Cancer Prevention Center, to help translate our findings to the clinic as quickly and efficiently as possible. Researcher Development Plan: My long-term career goal is to lead translational breast cance
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710077
Entities
People
- Vidya Sinha
Organizations
- United States Army
- University of Texas at Austin