Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population‐Based Study

Abstract

Although current evidence suggests potential antitumor activity of proton pump inhibitors (PPIs), there is no population-based evidence of an association between PPI use and subsequent breast cancer risks. We used an observational case-control study to examine the association between prior PPI use and breast cancer occurrence. Additional analysis examined dose-response and age-stratified associations of PPIs with breast cancer. This study used data from the Taiwan National Health Insurance Research Dataset. A total of 64,234 women diagnosed with breast cancer between 2004 and in 2013 were selected as cases. Controls were 64,234 women without cancer who were selected by matching them with cases on the basis of sociodemographic characteristics and widely prevalent comorbidities. Each study subject's claims data were tracked back for 5 years to determine precancer prescriptions of PPIs. Logistic regression modeling was used for the analysis. A total of 11,871 (9.24%) women had used PPIs within the prior 5 years, 8.06% and 10.42% among cases and controls, respectively. Breast cancer patients were 25% less likely to have had prior PPI exposure after adjustment for comorbidities that predispose to PPI exposure (95%CI 0.72-0.78) in the risk of breast cancer occurrence. A dose-response effect was also detected, with the highest effect, 35% lower PPI odds (95%CI 0.61-0.70) among patients in the highest exposure category. Our findings may suggest that women at a higher-than-average risk of breast cancer may benefit from PPI prescriptions if they have medical conditions that could benefit from PPIs.

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

“…NHE1 levels are higher in BC tissue than in normal breast tissue, and also in resistant BC cells than in sensitive cells, in a similar fashion to other PTs [ 4 , 10 , 51 , 55 , 56 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. Apart from NHE1 overexpression, carbonic anhydrases also have an important role in the pathogenesis of BC, like V-ATPase proton pumps, the Na + –HCO 3 − cotransporter (SLC4A7,NBCn1, MCTs, hypoxia and hypoxia-inducing factor 1 (HIF-1) [ 75 ].…”

“…Moreover, there is a significant increase in the survival of women who continue their PPI therapy after the completion of chemotherapy for BC [ 224 ]. On the other hand, women receiving PPI treatment for non-cancerous diseases have a reduced risk of developing BC [ 71 , 225 ]. Intermittent high dose PPI also improves MDR in metastatic BC [ 223 ].…”

A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer based upon its Hydrogen Ion Dynamics

“…More recent reports have shown that women affected by medical conditions suitable for PPI treatment, e.g. peptic diseases, have a reduced risk for developing BC [52,197]. Both studies were performed in a very large cohort of patients with very convincing results.…”

“…d) pH, proton transporters (PTs), proton pumps (PPs) and their inhibitors (PTIs and PPIs) [14,32,36,38,[41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]. e) pH and voltage gated sodium channels (VGSC) [56][57][58][59][60][61].…”

The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer

“…Several treatment modalities have been adopted to interfere with glycolysis, e.g., some pharmacological agents used to treat cancer via restoration of the mitochondrial function to support programmed cell death (apoptosis); some of these agents include Proton Pump Inhibitors (PPIs), Hydroxycitrate, NaHCO 3 , Lipoic acid, and could be extended to use some of the natural extracts, e.g., Fermented wheat germ extract FWGE [14,[57][58][59][60][61][62].…”