Angiogenesis in Hyperplasia to In-Situ Breast Cancers
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: Widespread implementation of mammographic screening has led to earlier detection of breast carcinomas. Today DCIS is estimated to comprise 20-40% of all mammogram-directed biopsies. The advance in screening technology may further shift the diagnosis to even earlier stages of breast cancer progression or even pre-malignancy. One theory is that invasive breast cancer results from a temporal and genetic sequence of several steps: from normal epithelium, through hyperplasia, progression to atypical hyperplasia (ADH), and then DCIS. In terms of eventual progression, DCIS can remain unchanged, or regress to previous normal state, or it may progress to become invasive cancer. However, little is known about the pathways and the involved stimulating factors leading to the transformation process.
 
 
 
 
 
 
 
 Formation of new blood vessels (angiogenesis) within tumors is essential for the growth and spread of cancer. In this study we will investigate the role of angiogenesis on disease progression from pre-malignant hyperplasia to in situ cancers. Many studies have shown that microvessel density in invasive breast cancer correlates with metastatic potential and patient survival. Since the ability of tumor cells to induce a vascular supply occurs early in the cell transformation, pre-malignant breast lesions may also induce a vascular supply to facilitate malignant transformation. We hypothesize that angiogenesis is associated with disease progression, thus it may have diagnostic and prognostic values. Specifically we will test that MRI measurements of angiogenesis can improve the specificity of mammography in differentiating benign hyperplasia from in situ cancers. 
 
 
 
 
 
 
 
 We will use dynamic contrast-enhanced magnetic resonance imaging (MRI) and immunohistochemical molecular biomarkers to characterize the angiogenic status from fibrocystic proliferation, atypical hyperplasia, to in situ breast cancer. One hundred patients with probable benign or probable malignant findings (with BIRADS 3 or 4- by mammography) will be enrolled. They will receive MRI examination prior to core biopsy or surgery. Then the specimens will be analyzed for molecular angiogenic markers, including expression of mutant tumor suppressor gene p53, Vascular Endothelial Growth Factor (VEGF), thrombospondin-1 (TSP1), and microvessel density (using CD31 and CD 105 staining). MRI vascular parameters and IHC biomarkers will be correlated with different disease stages to investigate their association with disease progression.
 
 
 
 
 
 
 
 To date, most of the angiogenesis research in breast cancer has been focused on invasive cancers. Little is known about its role on pre-malignant proliferative diseases and in situ cancers. The use of MRI in conjunction with IHC techniques may provide microscopic (IHC) and macroscopic (MRI) measurements of the vascularity status. We feel these methods complement each other, and may provide a more accurate assessment of angiogenesis. More complete clinical evaluation for breast lesions may lead to a better treatment and surveillance protocols for individual patients.