Universal Breast Cancer Antigens as Targets Linking Early Detection and Therapeutic Vaccination

: Molecular targets to facilitate early detection and preventative therapy for women at high risk for breast cancer have not been characterized. Two recently characterized intracellular enzymes -- human telomerase reverse transcriptase (hTERT) and the cytochrome P450 isoform 1B1 (CYP1B1), each overexpressed in >90% of invasive breast cancers but rarely found in normal tissue -- may fill this gap. Such targets, if found at the earliest time of malignant transformation, may be ideally suited not only for early detection but also cancer prevention by vaccination. A growing clinical experience in advanced cancer patients has underscored the safety and feasibility of vaccination strategies. The universal expression of hTERT and CYP1B1 provide an opportunity for both early detection and cancer vaccination. Objective/Hypothesis: We hypothesize that immunologic responses can be elicited in advanced breast cancer patients using vaccines incorporating hTERT, providing a safety and feasibility platform for ultimately vaccinating women at high risk for breast cancer. Although we have not found ductal lavage a feasible strategy for the detection of tumor antigens, we have made significant progress on vaccination strategies in women with metastatic breast cancer.