Common heartburn, cholesterol-lowering and blood pressure drugs are associated with severe adverse outcomes in patients with breast cancer, a large Australian-led study has shown.

Led by the University of South Australia and Flinders University, the study included data from more than 23,000 people across 19 breast cancer trials in what was the largest and most comprehensive analysis of its kind to date.

Findings showed proton pump inhibitors (PPIs) used to treat digestive diseases like gastro-­oesophageal reflux disease were significantly associated with poorer overall survival and progression-free survival for patients with breast cancer, as well as a 36% higher likelihood of severe (grade ≥ 3) adverse events.

“These findings are particularly concerning given the widespread overprescribing of PPIs in oncology care,” the researchers noted in Cancer Medicine [link here].

They suggested that plausible mechanisms for the association might be related to disruptions of the gut microbiota–immune system axis regulating systemic immune responses as well as PPIs altering the pharmacokinetics, and therefore efficacy, of anticancer drugs.

The study also found that beta-blockers, ACE inhibitors, angiotensin receptor blockers and calcium channel blockers were linked to higher rates of severe side effects but, reassuringly, these drug classes showed no significant effect on survival. The researchers said the findings supported use of these drugs when necessary with careful monitoring.

Statins and metformin used to manage high cholesterol and diabetes respectively demonstrated no significant impact on either survival or adverse events.

“Defining the impact of concomitant medicines on breast cancer outcomes is essential for guiding treatment decisions and improving patient care, particularly as advancements in therapy are extending survivorship after diagnosis,” the researchers said.

“Although our analysis does not establish direct mechanistic links, it raises important questions about routinely used concomitant medicines and the need for more personalised approaches to care that balance their potential risks and benefits.”

Lead author Dr Natansh Modi from the University of South Australia and Flinders University said the findings revealed a complex relationship between commonly prescribed medications and cancer outcomes.

Dr Natansh Modi

“Many women with breast cancer are also managing other chronic conditions such as high blood pressure, diabetes or acid reflux, meaning they are often taking multiple drugs at once,” Dr Modi said.

“Our results don’t suggest that people should stop taking their non-cancer medicines, but it underlines how important it is for doctors to regularly review patient medications because people are living longer and managing multiple health issues.”

Corresponding senior author, Associate Professor Ashley Hopkins from Flinders University, said the findings suggested that patients taking PPIs in oncology settings warranted closer attention in particular.

“It doesn’t mean that patients should cease their reflux medication without medical advice, but clinicians should be alert to potential risks and review whether PPIs are genuinely needed,” he said.

The researchers concluded that there should be a more personalised approach to breast cancer management that considered all concomitant drugs prescribed to a patient.

They also called for follow-up studies to further explore the underlying mechanisms behind the observed drug interactions, which could inform better guidance for the safe co-prescription of these medicines during cancer therapy.

The included clinical trials were sponsored by pharmaceutical companies including Lilly, Pfizer and Roche.