Concomitant PPI use linked to worse breast cancer outcomes

medwireNews: Taking proton pump inhibitors (PPIs) alongside anticancer therapy could worsen the overall survival (OS) and progression-free survival (PFS) of people with breast cancer, suggests a post-hoc analysis of data from clinical trials.

Concurrent PPI use was also associated with increased incidence of adverse events (AEs) of at least grade 3, and this was also the case for other medications including beta blockers (BBs), angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), and calcium channel blockers (CCBs).

“Although our analysis does not establish direct mechanistic links, it raises important questions about routinely used concomitant medicines and the need for more personalized approaches to care that balance their potential risks and benefits,” say Ashley Hopkins (Flinders University, Adelaide, South Australia) and co-researchers in Cancer Medicine.

They conducted an individual participant data meta-analysis of information on 23,211 patients enrolled in one of 19 breast cancer trials. The participants were aged a median of 52 years and 60% had early-stage breast cancer, while 40% had advanced disease.

At baseline, 12% were taking ACE inhibitors/ARBs, 8% were taking BBs, 8% were taking PPIs, 7% were taking statins, 5% were taking CCBs, and 3% were taking metformin.

After adjusting for age, BMI, estrogen receptor status, performance status, comorbidity count, and common comorbidities, the use of PPIs was significantly associated with worse OS and PFS than with no use, with a hazard ratio (HR) for death of 1.19 and a HR for progression or death of 1.11.

There was also a significant association between PPI use and an increased occurrence of grade 3 or worse AEs, with an odds ratio (OR) of 1.36 versus no use.

The risk for developing such AEs was similarly significantly increased with the concomitant use of CCBs, BBs, and ACE inhibitors/ARBs, with ORs relative to no use of 1.31, 1.21, and 1.13, respectively, but there was no significant association of any of these agents with OS or PFS.

And concurrent use of statins or metformin did not significantly worsen survival outcomes, nor raise the risk for AEs of at least grade 3 compared with no use.

Hopkins and colleagues say that “[t]he association between PPIs and poorer outcomes in this study aligns with a growing body of evidence suggesting potential risks associated with their use in patients with cancer,” and point out that these results “are particularly concerning given the widespread overprescribing of PPIs in oncology care.”

They continue: “Our findings emphasise the careful and judicious use of PPIs in patients with cancer, particularly those with breast cancer and highlight the necessity for ongoing research into their safety.”

The team notes that the study reassures “that BBs, ACE inhibitors/ARBs and CCBs do not worsen survival outcomes in patients with breast cancer and support their use when necessary,” but that “the increased risk of adverse events, potentially linked to cardiovascular, renal, or frailty mechanisms, also highlights the need for careful monitoring of patients taking these drugs, particularly those with additional risk factors for treatment-related adverse events.”

And the researchers conclude: “To build on these findings, future studies should aim to confirm these associations through prospective studies and explore the underlying mechanisms, including the potential impact of PPIs on gut microbiome dysregulation or their role as proxies for steroid use (since PPIs are commonly prescribed to prevent steroid-induced gastrointestinal irritation).”

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Cancer Med 2025; 14: e71320