Impact of proton pump inhibitors on the pathological complete response rate in luminal breast cancer during neoadjuvant therapy.

e12631 Background: Breast cancer (BC) is one of the most prevalent neoplasms, with a prognosis dependent on hormonal receptor (ER, PR) and HER2 expression. Neoadjuvant therapy (NAT) allows for tumor downsizing before surgery and assesses chemotherapy sensitivity. Pathological complete response (pCR) is a key prognostic marker, but rates are low in hormone receptor-positive (HR+) tumors. The enzyme fatty acid synthase (FASN), overexpressed particularly in HER2-positive tumors, has been associated with therapeutic resistance. Preclinical studies suggest that proton pump inhibitors (PPIs) may inhibit FASN and enhance chemosensitivity. Objective: To evaluate whether the concomitant use of PPIs (Esomeprazole) during NAT is associated with a higher pCR rate in patients with luminal breast cancer. Methods: A retrospective analysis was conducted on patients with luminal breast cancer (stages IIa–IIIb) treated at the Instituto Oncológico de Córdoba between January 2015 and January 2025. Patients who received NAT with or without continuous PPIs were included. Clinical variables, tumor characteristics, and pathological response were analyzed. Chi-square tests were applied (p < 0.05). Results: 130 patients were included; 61 used PPIs. The pCR rate was higher in the group that used PPIs (33.4% vs. 14.5%; p = 0.05). This difference was statistically significant in the Luminal B subtype (36.1% vs. 15.4%; p = 0.033) and was even more marked in the Luminal B/HER2+ subgroup (50% vs. 21.1%; p = 0.084). Conclusions: The use of PPIs during NAT was associated with a higher pCR rate in luminal breast cancer, with the greatest benefit observed in the Luminal B/HER2+ subtype. In this subgroup, the highest FASN expression is present, which could explain the increased chemotherapy sensitivity. These findings suggest a potential role for PPIs as therapeutic sensitizers.