Inhibiting Fatty Acid Synthase to Improve Efficacy of Neoadjuvant Chemotherapy

Study Summary

In preliminary laboratory science studies, the investigators show that proton pump inhibitors (PPIs) effectively inhibit human fatty acid synthase (FASN) and breast cancer cell survival. A preliminary retrospective study shows that PPI usage in breast cancer patients during chemotherapy significantly improved overall survival. The impact was most striking in patients with triple negative breast cancer (TNBC). Thus, PPIs may be repositioned as safe and effective breast cancer drugs to enhance the effect of chemotherapy. Many of the hurdles that slow progress from target, to lead compound, to investigational agent, to standard therapy are not barriers for the PPIs. The PPIs are FDA-approved, chronically used, and well tolerated so the investigators can move quickly from the laboratory to a proof of concept clinical trial. Incorporating the PPIs into standard care will require more than the investigators propose here, but the investigators have already plotted the additional steps needed to truly impact patient care. If successful, the data gathered in this proposal will lend support to and guide development of a definitive randomized trial.

Primary Outcome

pCR is defined as no invasive disease in the breast of axilla at the time of definitive surgery. A patient is considered to have FASN expression if the positivity was \>= 15% at the baseline or after 4-7 days of Omeprazole monotherapy. FASN expression is evaluated using immunohistochemistry in core biopsy samples. The percent of patients with FASN expression that have pCR will be calculated with an exact 95% confidence interval.

Interventions

• DRUG Omeprazole