{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T08:27:35Z","timestamp":1761899255925,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Endocrine therapy combined with CDK4\/6 inhibitors are widely recognized as the standard first-line approach for treating hormone receptor-positive HER2-negative (HR+\/HER2\u2212) metastatic breast cancer (mBC). Nonetheless, potential pharmacokinetic interactions\u2014particularly with proton pump inhibitors (PPIs)\u2014have raised concerns about reduced drug bioavailability and compromised therapeutic efficacy. Materials and Methods: This retrospective analysis included 92 patients with HR+\/HER2\u2212 mBC who received either ribociclib or palbociclib between 2019 and 2024 at a single tertiary care center. Patients were stratified according to whether they were concurrently using PPIs during CDK4\/6 inhibitor treatment. The primary endpoint assessed was progression-free survival (PFS). The study population was dominated by ribociclib users, and the results primarily apply to ribociclib; the palbociclib analyses are descriptive only due to the very small numbers (n = 6). Results: The median PFS was significantly shorter in patients who received concomitant PPI therapy compared with those who did not (5.6 vs. 24.4 months; p &lt; 0.001). Multivariable analysis identified PPI use, endocrine resistance, and the presence of three or more metastatic sites as independent predictors of reduced PFS. In the ribociclib-only cohort (n = 86), the association persisted (adjusted HR 6.36, 95% CI 3.02\u201313.37, p &lt; 0.001). No notable differences in toxicity profiles were observed between the groups. Conclusions: In this ribociclib-dominant real-world cohort, concomitant PPI use was associated with shorter PFS, and the findings primarily apply to ribociclib. Given the potential for confounding by the indication\/comorbidity inherent to retrospective studies, the results should be interpreted as associational. These data support the cautious use of non-essential PPIs during ribociclib therapy and underscore the need for prospective agent-specific pharmacokinetic studies.<\/jats:p>","DOI":"10.3390\/medicina61111960","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:29:42Z","timestamp":1761895782000},"page":"1960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing the Influence of Proton Pump Inhibitors on Clinical Outcomes in Hormone Receptor-Positive Metastatic Breast Cancer Patients Receiving CDK4\/6 Inhibitors: Evidence from a Ribociclib-Dominant Cohort"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-2087","authenticated-orcid":false,"given":"Enes","family":"Erul","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Ankara University Faculty of Medicine, Ankara 06620, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nejat Emre","family":"\u00d6ks\u00fcz","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Ankara University Faculty of Medicine, Ankara 06620, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7531-7817","authenticated-orcid":false,"given":"Erman","family":"Akkus","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Ankara University Faculty of Medicine, Ankara 06620, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u0131nar Kubilay","family":"Tolunay","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Ankara University Faculty of Medicine, Ankara 06620, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elif Berna","family":"K\u00f6ksoy","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Ankara University Faculty of Medicine, Ankara 06620, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatime Arzu","family":"Yasar","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Ankara University Faculty of Medicine, Ankara 06620, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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