SUMMARY Triple negative breast cancer (TNBC) represents 20% of the breast cancer (BC) cases in the US. TNBC patients have a poor recurrence-free, overall survival rate, and limited treatment options. The Mediterranean olive oil-rich diet is documented to reduce BC incidence. (-)-Oleocanthal (OC) is a natural phenolic exclusively occurring in extra-virgin olive oil (EVOO). It showed selective anti-BC activities. Dysregulated HGF/MET pathway, the validated major OC molecular target, correlates with initiating aggressive and recurrent TNBC profile. A unique OC taste-masked, dissolution enhancing and chemical integrity maintaining solid dispersion formulation (OC-X) was developed and characterized. The central hypothesis is that oral OC-X will be effective as a preventive and therapeutic to control locoregional TNBC recurrence. The following aims will test this hypothesis. Aim 1: Perform dose dependent studies to determine the optimal effective dose of orally administered OC-X on tumor recurrence in nude mice and pharmacokinetics in Swiss albino mice. This Aim will assess efficacy of OC-X in preventive, treatment, after completion of paclitaxel neoadjuvant regimen and bioavailability. Aim 2: Perform dose dependent studies to determine the optimal effective dose of orally administered OC-X on tumor recurrence in MMTV-PyMT transgenic mouse model. This human-mimicking heterogenic model will be used to assess recurrence (after surgical excision of early mammary gland tumors) and metastasis inhibitory effects of OC-X. Expected outcomes: The intake of OC in EVOO over human history and the lack of other safe therapeutic alternatives qualify this important bioactive natural product for long-term use to prevent breast and MET-dependent cancers recurrence. Validation of an OC nutraceutical product will facilitate its commercialization for long-term use to prevent recurrence in BC patients and survivors.