Omeprazole helps inhibit fatty acid synthase activity in triple-negative breast cancer
Fatty acid synthase (FASN) is commonly expressed in operable triple-negative breast cancer (TNBC) and is associated with a poor prognosis, but omeprazole can hamper FASN activity, which may potentially boost the efficacy of neoadjuvant chemotherapy, according to the results of a phase II study.
Forty-two patients (median age 51 years) with operable TNBC underwent a 4–7-day course of omeprazole 80 mg orally twice daily prior to initiating neoadjuvant anthracycline–taxane-based chemotherapy. The proton pump inhibitor therapy was continued until surgery.
Researchers evaluated the efficacy of omeprazole in relation to pathologic complete response (pCR), the primary study endpoint, in patients with baseline FASN overexpression (FASN+). They also looked at pCR in all surgery patients, change in FASN expression, enzyme activity, and downstream protein expression after omeprazole monotherapy, safety, and limited omeprazole pharmacokinetics.
In the cohort, most patients had ≥cT2 (79 percent) and ≥N1 (52 percent) disease. Twenty-nine out of 34 evaluable patients (85 percent) showed FASN overexpression prior to chemotherapy initiation.
The pCR rate was 72.4 percent (95 percent confidence interval [CI], 52.8–87.3) in the FASN+ group and 74.4 percent (95 percent CI, 57.9–87.0) in the all-surgery group.
Peak omeprazole concentration was significantly higher than the half-maximal inhibitory concentration (IC50) for FASN inhibition observed in preclinical testing. Accordingly, omeprazole monotherapy led to a significant reduction in FASN expression (mean change, 0.12; p=0.02).
Omeprazole was well tolerated, and there were no grade ≥3 toxicities reported.