Breast cancer (BC) recurrence represents a challenge for survivors who have had their primary
tumors surgically excised, and/or have completed
radiation, neoadjuvant, or adjuvant therapeutic regimens. Current BC treatments mostly lack the ability to reduce the risk of disease recurrence. About 70% of BC patients will subsequently suffer disease relapse, manifesting as local, regional, or distant
tumor recurrence, which clearly underscores the urgent need to discover novel recurrence inhibitors. (-)-
Oleocanthal (OC) is a natural phenolic, found so far exclusively in extra-virgin
olive oil (EVOO). OC exerts documented bioactivities against diverse
cancer types,
inflammation, and
neurodegenerative diseases. Herein we report the novel activity of daily oral treatment with OC (10 mg/kg) in preventing BC locoregional recurrence in a nude mouse xenograft model generated by orthotopic inoculation with BT-474 cells as a
luminal type B model. We further report inhibition of
tumor recurrence by OC after completion of a
lapatinib neoadjuvant regimen. However, in a recurrence model of
triple-negative breast cancer (TNBC), OC treatment (10 mg/kg) did not effectively prevent
tumor recurrence, but rather, was seen to significantly reduce the growth of recurrent
tumors as compared to vehicle control-treated animals. Inhibition of
tumor recurrence was associated with significant serum level reductions of the human BC recurrence marker CA 15-3 at the study end in animals treated with OC. OC treatment upregulated the expression of the epithelial marker
E-cadherin and downregulated the levels of the mesenchymal marker
vimentin in recurrent
tumors vs. untreated control animals. OC treatment also reduced the activation of MET and HER2 receptors, as indicated by reduced phosphorylation levels of these
proteins in recurrent
tumors vs. controls. Collectively, the results of our studies provide the first evidence for suppression of BC
tumor recurrence by oral OC treatment in an animal model for such recurrence, and furthermore, highlight favorable prospects for this natural product to emerge as a first-in-class BC recurrence inhibitor.