Improved Epigenetic Signatures for Breast Cancer Prognosis and Treatment Selection

Background & Unmet Need

• Breast cancer is the second leading cause of cancer deaths in women, with more than 40,000 deaths annually
• Immunohistochemically defined markers, including estrogen (ER) and progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), and the proliferation marker Ki67, play a major role in therapy recommendations
• There are currently several commercially-available prognostic molecular signatures (e.g., Oncotype, Endopredict, Prosigna, BCI) that are used for predicting breast cancer recurrence
• However, these tests are only recommended by ASCO for use in lymph node negative, early stage, ER-positive and HER-negative breast cancers
• Unmet Need: Need for molecular signatures that are applicable to all types of breast cancer, such as triple-negative breast cancer (TNBC) and HER2+

Technology Overview

• The Technology: Epigenetic tumor (ET) signature was identified as a prognostic marker for breast cancer independent of patient characteristics
• The Discovery: ZNF92 overexpression is strongly associated with breast cancer and can predict patient outcomes
• PoC Data: The ET-9/ZNF92 signature identified patients with 8.7 years shorter overall survival (p=1.56e-5) and 6.3 years shorter relapse free survival (p=1.63e-4)
• ET/ZNF92 correlates with outcome in lymph-node positive, HER2+, post-chemotherapy and triple-negative breast cancers. These features distinguish ET-9/ZNF92 since standard prognostic signatures correlate with outcome only in ER-positive, HER2-negative, and lymph-node negative breast cancers
• ZNF92 over-expression is even more specific for breast cancer compared to common benchmarks such as estrogen receptor (ER) and HER2
• The inventor has developed a second signature that is synergistic with ET/ZNF92 (manuscript in preparation)

Technology Applications

• Assay to identify breast cancer patients at high risk of relapse and shorter survival
• Assay to identify patients who are most likely to benefit from HDAC inhibitor therapy
• Identifies ZNF92 as a novel target for breast cancer drug development

Technology Advantages

• Outperforms existing commercial tests (Oncotype, Endopredict, Prosignia, BCI, and Mammaprint)
• Prognostic value of assay functions independently of patient demographics and tumor characteristics
• Accurately identifies breast cancer patients with 6-8 years shorter relapse-free and overall median survival that may benefit from additional or alternative therapies