Distinguishing Benign from Malignant Breast Lesions: Does Breast Interstitial Fluid Hold the Answers?
Abstract
Mammography is currently the best available tool for general breast cancer screening. While mammography is effective at detecting some breast cancers, there are limitations to this technology including a number of cancers that are missed (for example, in dense breast tissue), and detection of many benign masses lead to stressful, uncomfortable, and often unnecessary biopsies and surgeries (e.g., overdiagnosis and overtreatment). Better tools are needed to improve breast cancer detection and distinguish women with benign masses from women with breast cancer in a low burden manner. This project will address the Department of Defense Breast Cancer Research Program s Overarching Challenge: conquer the problems of overdiagnosis and overtreatment. Interstitial fluid is a liquid that bathes the cells in the body. We hypothesize that proteins in breast interstitial fluid reflect the tissue environment and differ in areas near benign masses, malignant masses, and normal tissue. To date, common methods of collecting interstitial fluid have involved removing tissue from the body for fluid collection, or invasive methods requiring the implantation of foreign objects. Our approach uses a novel device that is placed on a woman s breast to collect interstitial fluid and causes minimal discomfort (equivalent to a mosquito bite). Interstitial fluid will be collected from 50 women who have been diagnosed with suspicious breast masses. Each study participant will wear a collection device on an area of the breast close to the mass and another device on the matching location on the opposite mass-free breast. After 1 hour, the devices will be removed and the collected interstitial fluid (less than a teaspoon) will analyzed in the lab. Protein measurements will be made on the collected fluid in two ways. First, a microchip sensor (previously used to detect ovarian cancer biomarkers) will measure levels of a specific protein that has been shown to have increased levels in interstitial fluid from tumor tissue compared to interstitial fluid from normal tissue. Results of these measurements will be compared with clinical findings (i.e., distance of the tumor from the skin as measured by ultrasound, clinical lab diagnosis, hormone receptor status, 10-year and lifetime risk of breast cancer). Second, we will use state-of-the-art technology to measure the levels of thousands of proteins in interstitial fluid to identify proteins that can be found in this novel sample type (all prior work was with invasive tools or conducted in tissue samples after they were removed from the breast) and which ones are significantly different when comparing fluid from benign or cancerous breasts to breasts without any masses or lumps. Ultimately, the interstitial fluid collection device would be coupled with the microchip sensor for a portable, integrated, and point-of-care diagnostic system that would be accessible to women worldwide. This study design also benefits from the elegant advantage that each woman serves as her own control when measurements are made for pairwise comparisons between breasts. We anticipate that this early work has the potential to help all women undergoing breast cancer screening. Depending on the performance of the measurements, potential clinical scenarios include a precursor screening to mammography, a companion method with mammography to better distinguish benign from malignant breast masses without invasive procedures, and/or measuring specific proteins associated with aggressive breast cancer. There are many potential benefits including identifying cancers that would be missed by mammography, monitoring of early disease to reduce side effects from overtreatment of indolent disease, and/or identifying masses that are benign thereby eliminating the need for stressful biopsies and/or surgeries. The potential risks are minimal and include a skin rash. If successful, a patient-related outcome could be expected within 5 yea
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510646
Entities
People
- Sharon J Pitteri
Organizations
- Stanford University
- United States Army