Terpenoids and breast cancer chemoprevention

Cancer chemoprevention is defined as the use of natural or synthetic agents that reverse, suppress or arrest carcinogenic and/or malignant phenotype progression towards invasive cancer. Phytochemicals obtained from vegetables, fruits, spices, herbs and medicinal plants, such as terpenoids, carotenoids, flavanoids, phenolic compounds, and other groups of compounds have shown promise in suppressing experimental carcinogenesis in various organs. Recent studies have indicated that mechanisms underlying chemopreventive action may include combinations of anti-oxidant, anti-inflammatory, immune-enhancing, and anti-hormone effects. Further, modification of drug-metabolizing enzymes, and influences on cell cycling and differentiation, induction of apoptosis, and suppression of proliferation and angiogenesis that play a role in the initiation and secondary modification of neoplastic development, have also been under investigation as possible mechanisms. This review will highlight the biological effects of terpenoids as chemopreventive agents on breast epithelial carcinogenesis, and the utility of intermediate biomarkers as indicators of premalignancy. Selected breast chemoprevention trials are discussed with a focus on strategies for trial design, and clinical outcomes. Future directions in the field of chemoprevention are proposed based on recently acquired mechanistic insights into breast carcinogenesis.