Abstract B018: Physical tumor microenvironment biomarkers to predict DCIS progression, upstaging, and early metastasis

Ductal carcinoma in situ (DCIS) is defined as a neoplastic proliferation of epithelial cells confined to the mammary ductal-lobular system. Although metastasis can occur at the very early stages of DCIS, the majority of metastatic breast cancers are believed to arise through a years-long process of somatic evolution within the physical constraints of milk ducts, characterized by the accumulation of heritable genetic and epigenetic changes. While these genetic alterations during breast carcinogenesis have been extensively studied without any outcome that can be used as a clinical biomarker, less attention has been paid to the microenvironmental conditions that select for these genotypes. We have demonstrated that evolving pre-cancerous hyperplastic breast cells are selected under physical tumor microenvironment conditions such as hypoxia, acidosis, and starvation. We have also shown that these harsh conditions select cells with more aggressive phenotypes. We have developed several markers for the adapted cells under these harsh conditions such as LAMP2b for acidosis or CA9 for hypoxia. We, therefore, hypothesize that the expression of physical microenvironment adaptation proteins (PMA) can differentiate indolent from aggressive DCIS and that this can be used for decision support. DCIS can be detected by screening mammography followed by a percutaneous Biopsy for pathologic confirmation, which may be followed by surgery +/- adjuvant therapy. Citation Format: Mehdi Damaghi, Zainab Raza, Rana Adil Farman, JiDong Bai, Joel Saltz, Bethany L. Niell. Physical tumor microenvironment biomarkers to predict DCIS progression, upstaging, and early metastasis [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B018.