Stratifying DCIS Biopsies for Risk of Future Tumor Formation
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: While it is estimated that ~62,000 women were diagnosed with pre-cancers or pre-malignant lesions such as ductal carcinoma in situ (DCIS) in 2007, only 15% of these women will subsequently develop invasive breast cancer with potential to die of the disease. However, the vast majority of women diagnosed with DCIS undergo the same regimen of full breast removal (mastectomy), partial mastectomy or partial mastectomy followed by radio-, chemo-therapy and/or hormone drugs. Thus, many thousands of women are treated unnecessarily with additional radiation, hormonal therapy, and/or mastectomy in order to prevent the progression of an invasive cancer that will not, in fact, occur. This causes unnecessary suffering and side effects in a majority of otherwise-healthy women and places unnecessary demands on healthcare systems. Additionally, ~10% of DCIS patients do not receive adequate intervention, since they develop tumors even when the DCIS is removed.
 
 
 
 
 
 
 
 Our goal is the development of a rapid, inexpensive prognostic clinical test that will provide individual risk information for all women diagnosed with DCIS.
 
 
 
 
 
 The general methodology: Recently, we successfully found several biomarkers that, when expressed in DCIS, accurately predict formation of aggressive invasive tumors (called basal-like breast cancers) years before they form, as well as markers that identify women who will not develop future breast cancers after a pre-cancer diagnosis. Our general methodology was to use novel biological insights from basic studies of how
 
 cancer forms and grows to provide us with clues to identify markers that predict future invasive cancers. After the candidate biomarkers are hypothesized, they are tested in biopsy samples that were collected years ago in women that were diagnosed with DCIS and elected to have a subsequent lumpectomy. Standard practice at that time did not propose radiation or hormonal drugs. These women have been contacted through the years to monitor their health and determine if subsequent breast cancer developed. Since it is known which biopsies came from women who did or did not develop a subsequent invasive breast cancer, we can determine if our candidate markers are useful by testing them on the biopsies and evaluating their ability to accurately identify which women developed breast cancer.
 
 
 
 
 
 
 
 For over four decades clinical investigators have tried to identify markers that would predict which women diagnosed with DCIS would be among the ~15% to develop a future invasive tumor. They looked for markers in the size, shape and pattern of the DCIS with no success. In the more recent molecular era, they have evaluated several molecular markers, again with no success. Our biological approach, using a unique and well-studied tissue culture model system, provided the first clues to this important clinical problem. Our analysis of how these human breast cells acquire cancer properties has provided insights for the prediction of future tumor formation. We propose to use this innovative model system to identify additional candidate markers that will provide information about the remaining fraction of biopsies that do not express the markers we have already identified. Validation of these additional markers would allow us to develop the first test that would tell a woman diagnosed with DCIS about her risk of future breast cancer.