Researchers have found in an observational study that breast cancer patients using proton pump inhibitors (PPIs) alongside anti-cancer therapies had poorer survival outcomes. Concurrent use of PPIs and other common medications was also linked to a higher risk of severe (grade ≥3) adverse events. However, they advised that while patients should not discontinue medications without medical guidance, clinicians should carefully review the necessity of PPI use during cancer treatment. The study was published in the journal of Cancer Medicine by Natansh M. and colleagues.
Though cancer-directed therapies are extensively studied, the impact of non-cancer medications on cancer outcomes is less well understood. In fact, many patients with breast cancer have been taking medications for various chronic conditions, which include hypertension, diabetes, and gastrointestinal disorders. Understanding the potential interplay between these drugs and tumor biology and response to therapy is critical to optimizing overall care. This large pooled analysis aimed to determine whether commonly used non-cancer medications impact survival and toxicity outcomes in patients with breast cancer.
Individual participant data from 19 breast cancer clinical trials, including 23,211 patients, were used to conduct a pooled analysis. The associations of various medication classes with OS, PFS, and grade ≥3 adverse events were estimated by Cox proportional hazards models and logistic regression analyses. Robust adjustments were made in the analyses for patient demographics, cancer characteristics, and comorbid conditions to minimize confounding.
Results
These analyses demonstrated that PPI use was associated with significantly worse survival outcomes.
Compared with nonusers, patients who used PPIs had a 19% increased risk of death (HR 1.19, 95% CI: 1.08–1.30) and an 11% increased risk of disease progression (HR 1.11, 95% CI: 1.02–1.21).
The use of PPIs increased the risk of severe adverse events, with an odds ratio of 1.36 (95% CI: 1.21–1.53) for grade ≥3 toxicities.
Other cardiovascular drugs, such as beta-blockers, ACE inhibitors/ARBs, and calcium channel blockers, were also linked with increased rates of adverse events but did not notably affect survival.
Statins and metformin are widely hypothesized to possess anti-cancer properties, but demonstrated no statistically significant association with either survival or toxicity outcomes in this large dataset.
This large, pooled analysis showed that proton pump inhibitor use was associated with poorer survival and more toxicity in breast cancer patients. These findings emphasize the importance of incorporating medication management into comprehensive breast cancer care in pursuit of optimal long-term outcomes.
Reference:
Modi, N. D., Abuhelwa, A. Y., Kuderer, N. M., Li, L. X., Lyman, G. H., Koczwara, B., Kichenadasse, G., Selth, L. A., Rickard, C., Haseloff, M., Vitry, A., Woodman, R., Logan, J. M., Ng, H. S., Wiese, M. D., McKinnon, R. A., Rowland, A., Sorich, M. J., & Hopkins, A. M. (2025). Associations of commonly used concomitant medications with survival and adverse event outcomes in breast cancer. Cancer Medicine, 14(21), e71320. https://doi.org/10.1002/cam4.71320
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