{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:09:32Z","timestamp":1765811372499,"version":"3.48.0"},"reference-count":15,"publisher":"FapUNIFESP (SciELO)","issue":"12","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Assoc. Med. Bras."],"abstract":"<jats:p>SUMMARY  OBJECTIVE: The prognosis of metastatic breast cancer has improved with new targeted therapies like cyclin-dependent kinase 4\/6 inhibitors. Renin-angiotensin system inhibitors, such as direct renin inhibitors, angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors are frequently used to manage hypertension and heart failure. However, recent research indicates that they may also provide potential benefits in cancer therapy. The combination of renin-angiotensin system inhibitors with cyclin-dependent kinase 4\/6 inhibitors is an emerging area of interest in cancer research. Our hypotesis that, by inhibiting angiogenesis, renin-angiotensin system inhibitors may reduce tumor growth and improve the effectiveness of cyclin-dependent kinase 4\/6 inhibitors by cutting off the supply of nutrients and oxygen to the tumor.  METHODS: Metastatic breast cancer patients treated with cyclin-dependent kinase 4\/6 inhibitors were enrolled and retrospectively divided according to angiotensin-converting enzyme inhibitor\/angiotensin II receptor blocker use: angiotensin-converting enzyme inhibitor\/angiotensin II receptor blocker (+) and angiotensin-converting enzyme inhibitor\/angiotensin II receptor blocker (-). Progression-free survival and overall survival were defined as primary and secondary endpoints. The effect of categorized data on progression-free survival and overall survival was determined by Cox regression analyses.  RESULTS: Estimated median progression-free survival (HR 0.61, 95%CI 0.34\u20130.94; p = 0.041) and overall survival (HR 0.71, 95%CI 0.49-0.79; p: 0.01) were statistically significantly longer in the angiotensin-converting enzyme inhibitor\/angiotensin II receptor blocker (+) group than in the angiotensin-converting enzyme inhibitor\/angiotensin II receptor blocker (-) group.  CONCLUSION: Concomitant use of renin-angiotensin system inhibitors and cyclin-dependent kinase 4\/6 inhibitors may have beneficial oncological effects in patients with breast cancer beyond their cardiovascular indications.<\/jats:p>","DOI":"10.1590\/1806-9282.20251164","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:06:00Z","timestamp":1765811160000},"source":"Crossref","is-referenced-by-count":0,"title":["Combination of cyclin-dependent kinase 4\/6 inhibitors and renin-angiotensin system inhibitors in breast cancer treatment: a promising therapeutic approach"],"prefix":"10.1590","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1008-2527","authenticated-orcid":false,"given":"Emel","family":"Mutlu","sequence":"first","affiliation":[{"name":"Erciyes University,  T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9612-9970","authenticated-orcid":false,"given":"Mevl\u00fcde","family":"\u0130nan\u00e7","sequence":"additional","affiliation":[{"name":"Erciyes University,  T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"530","published-online":{"date-parts":[[2025]]},"reference":[{"issue":"7","key":"ref1","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.3390\/biomedicines13071779","article-title":"Immunomodulatory effects of RAAS inhibitors: beyond hypertension and heart failure","volume":"13","author":"Haliga RE","year":"2025","journal-title":"Biomedicines"},{"issue":"21","key":"ref2","doi-asserted-by":"crossref","first-page":"5302","DOI":"10.3390\/cancers14215302","article-title":"Exploring the biology of cancer-associated fibroblasts in pancreatic cancer","volume":"14","author":"Bryce AS","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"3","key":"ref3","first-page":"884","article-title":"The role of the renin-angiotensin system inhibitors in malignancy: a review","volume":"11","author":"Yang J","year":"2021","journal-title":"Am J Cancer Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.xjon.2024.01.014","article-title":"An angiotensin system inhibitor (losartan) potentiates antitumor efficacy of cisplatin in a murine model of non-small cell lung cancer","volume":"18","author":"Tang H","year":"2024","journal-title":"JTCVS Open"},{"issue":"13","key":"ref5","article-title":"Do renin-angiotensin system inhibitors influence the recurrence, metastasis, and survival in cancer patients?: evidence from a meta-analysis including 55 studies","volume":"96","author":"Sun H","year":"2017","journal-title":"Medicine (Baltimore)"},{"issue":"1","key":"ref6","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12885-022-09200-4","article-title":"Angiotensin blockade therapy and survival in pancreatic cancer: a population study","volume":"22","author":"Keith SW","year":"2022","journal-title":"BMC Cancer"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"100510","DOI":"10.1016\/j.clinsp.2024.100510","article-title":"Comprehensive diagnosis of advanced-stage breast cancer: exploring detection methods, molecular subtypes, and demographic influences - a cross-sectional study","volume":"79","author":"Rivas FWS","year":"2024","journal-title":"Clinics (Sao Paulo)"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.ijbiomac.2022.07.156","article-title":"Structure-guided design and development of cyclin-dependent kinase 4\/6 inhibitors: a review on therapeutic implications","volume":"218","author":"Yousuf M","year":"2022","journal-title":"Int J Biol Macromol"},{"issue":"84","key":"ref9","doi-asserted-by":"crossref","first-page":"35500","DOI":"10.18632\/oncotarget.26174","article-title":"Renin-angiotensin inhibitors reprogram tumor immune microenvironment: a comprehensive view of the influences on anti-tumor immunity","volume":"9","author":"Vallejo-Ardila DL","year":"2018","journal-title":"Oncotarget"},{"issue":"4","key":"ref10","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1007\/s12094-020-02488-3","article-title":"Renin-angiotensin system and cancer: epidemiology, cell signaling, genetics and epigenetics","volume":"23","author":"Afsar B","year":"2021","journal-title":"Clin Transl Oncol"},{"issue":"9","key":"ref11","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3109\/07357907.2011.616252","article-title":"Reduced risk of breast cancer recurrence in patients using ACE inhibitors, ARBs, and\/or statins","volume":"29","author":"Chae YK","year":"2011","journal-title":"Cancer Invest"},{"issue":"11","key":"ref12","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1111\/jgh.12988","article-title":"Angiotensin receptor blockers improve survival outcomes after radiofrequency ablation in hepatocarcinoma patients","volume":"30","author":"Facciorusso A","year":"2015","journal-title":"J Gastroenterol Hepatol"},{"issue":"1","key":"ref13","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1186\/s12885-022-09919-0","article-title":"Impact of renin-angiotensin system inhibitors on the survival of patients with rectal cancer","volume":"22","author":"Zeman M","year":"2022","journal-title":"BMC Cancer"},{"issue":"10","key":"ref14","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41568-023-00604-3","article-title":"Therapeutic resistance to anti-oestrogen therapy in breast cancer","volume":"23","author":"Will M","year":"2023","journal-title":"Nat Rev Cancer"},{"issue":"10","key":"ref15","doi-asserted-by":"crossref","DOI":"10.1590\/1806-9282.6910edi","article-title":"Breast cancer survivals and hormone therapy: estrogen and melatonin","volume":"69","author":"Soares J\u00fanior JM","year":"2023","journal-title":"Rev Assoc Med Bras (1992)"}],"container-title":["Revista da Associa\u00e7\u00e3o M\u00e9dica Brasileira"],"original-title":[],"link":[{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_pdf&pid=S0104-42302025001200621&tlng=en","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:06:02Z","timestamp":1765811162000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S0104-42302025001200621&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":15,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025]]}},"alternative-id":["S0104-42302025001200621"],"URL":"https:\/\/doi.org\/10.1590\/1806-9282.20251164","relation":{},"ISSN":["1806-9282","0104-4230"],"issn-type":[{"value":"1806-9282","type":"electronic"},{"value":"0104-4230","type":"print"}],"subject":[],"published":{"date-parts":[[2025]]},"article-number":"e20251164"}}