{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T17:56:05Z","timestamp":1777139765204,"version":"3.51.4"},"reference-count":19,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T00:00:00Z","timestamp":1580428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 2016, project code 19174"],"award-info":[{"award-number":["IG 2016, project code 19174"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rete Oncologica del Piemonte e della Valle d'Aosta","award":["Cardiorete"],"award-info":[{"award-number":["Cardiorete"]}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente"],"award-info":[{"award-number":["Ricerca Corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Angiotensin Converting Enzyme inhibitors (ACEis) and beta-blockers (BB) are suggested to prevent and treat trastuzumab-related cardiac toxicity. We performed a prospective clinical trial in women experiencing mild cardiac toxicity (MCT) while on adjuvant treatment with trastuzumab. Methods: MCT was defined as an asymptomatic absolute decrease in LVEF of \u2265 10 percentage units to &gt;50%. Treatment consisted of enalapril 2.5 mg bid and carvedilol 3.75 mg bid, which were up-titrated to 10 mg bid for the enalapril and 6.25 mg bid of carvedilol. In patients receiving study drug, the primary study end-point was LVEF recovery, which was defined as a post-trastuzumab LVEF returning to no less than \u22125 percentage points of the baseline value. Results: 103 patients were enrolled, 100 started trastuzumab, and 98 completed the planned treatment. Sixteen patients (16%) had MCT and received study drugs until trastuzumab completion. None of these patients achieved a post-trastuzumab LVEF recovery. Nevertheless, treated patients had significantly higher median LVEF recovery from nadir to post-trastuzumab LVEF in (8% points vs. 4% points, respectively, p = 0.004), resulting in no difference in post-treatment LVEF values compared to patients without MCT. Conclusion: Treatment of MCT with ACEis and BB allows faster LVEF recovery from nadir values and should be further studied in this setting.<\/jats:p>","DOI":"10.3390\/cancers12020327","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T11:55:56Z","timestamp":1580471756000},"page":"327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Treatment with Beta-Blockers and ACE-Inhibitors in Breast Cancer Patients Receiving Adjuvant Trastuzumab-Based Therapy and Developing Mild Cardiac Toxicity: A Prospective Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Elena","family":"Geuna","sequence":"first","affiliation":[{"name":"Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Medical School, University of Turin, 10124 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"Martinello","sequence":"additional","affiliation":[{"name":"Oncologia Medica, Ospedale Cardinal Massaia, 14100 Asti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Garino","sequence":"additional","affiliation":[{"name":"Medical School, University of Turin, 10124 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Bonzano","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4851-5938","authenticated-orcid":false,"given":"Danilo","family":"Galizia","sequence":"additional","affiliation":[{"name":"Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7328-5877","authenticated-orcid":false,"given":"Annamaria","family":"Nuzzo","sequence":"additional","affiliation":[{"name":"Clinical Research Office, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5835-5638","authenticated-orcid":false,"given":"Paola","family":"Berchialla","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Cliniche e Biologiche, University of Turin, 10124 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Becco","sequence":"additional","affiliation":[{"name":"Medical School, University of Turin, 10124 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Mangioni","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"De Zarlo","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4231-2291","authenticated-orcid":false,"given":"Filippo","family":"Montemurro","sequence":"additional","affiliation":[{"name":"Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1126\/science.3798106","article-title":"Human breast cancer: Correlation of relapse and survival with amplification of the HER-2\/neu oncogene","volume":"235","author":"Slamon","year":"1987","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1126\/science.2470152","article-title":"Studies of the HER-2\/neu proto-oncogene in human breast and ovarian cancer","volume":"244","author":"Slamon","year":"1989","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/14656566.2018.1543406","article-title":"What is the best pharmacotherapeutic strategy for HER-2 positive breast cancer?","volume":"20","author":"Giannone","year":"2019","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3859","DOI":"10.1200\/JCO.2006.09.1611","article-title":"Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial","volume":"25","author":"Suter","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s10549-019-05453-z","article-title":"A pooled analysis of the cardiac events in the trastuzumab adjuvant trials","volume":"179","author":"Ponde","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/eurheartj\/ehw211","article-title":"2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)","volume":"37","author":"Zamorano","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1200\/JCO.2015.65.7916","article-title":"Role of troponins I and T and N-terminal prohormone of brain natriuretic peptide in monitoring cardiac safety of patients with early-stage human epidermal growth factor receptor 2-positive breast cancer receiving trastuzumab: A herceptin adjuvant study cardiac marker substudy","volume":"35","author":"Zardavas","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.annonc.2019.10.023","article-title":"Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations","volume":"31","author":"Curigliano","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10549-018-5058-6","article-title":"A real-world study of cardiac events in > 3700 patients with HER2-positive early breast cancer treated with trastuzumab: Final analysis of the OHERA study","volume":"174","author":"Lidbrink","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"727","DOI":"10.4143\/crt.2018.262","article-title":"Early decline in left ventricular ejection fraction can predict trastuzumab-related cardiotoxicity in patients with breast cancer: A study using 13 years of registry data","volume":"51","author":"Kim","year":"2019","journal-title":"Cancer Res. Treat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.breast.2018.06.001","article-title":"Fluctuation of the left ventricular ejection fraction in patients with HER2-positive early breast cancer treated by 12 months of adjuvant trastuzumab","volume":"41","author":"Jacquinot","year":"2018","journal-title":"Breast"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1001\/jamaoncol.2016.1726","article-title":"Angiotensin II-receptor inhibition with candesartan to prevent trastuzumab-related cardiotoxic effects in patients with early breast cancer: A randomized clinical trial","volume":"2","author":"Boekhout","year":"2016","journal-title":"Jama Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1093\/eurheartj\/ehw022","article-title":"Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): A 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol","volume":"37","author":"Gulati","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1161\/CIRCULATIONAHA.106.635144","article-title":"Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition","volume":"114","author":"Cardinale","year":"2006","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1016\/j.jacc.2006.07.052","article-title":"Protective effects of carvedilol against anthracycline-induced cardiomyopathy","volume":"48","author":"Kalay","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1200\/JCO.2016.68.7830","article-title":"Multidisciplinary approach to novel therapies in cardio-oncology research (MANTICORE 101-Breast): A Randomized trial for the prevention of trastuzumab-associated cardiotoxicity","volume":"35","author":"Pituskin","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1016\/j.jacc.2019.03.495","article-title":"Randomized trial of lisinopril versus carvedilol to prevent trastuzumab cardiotoxicity in patients with breast cancer","volume":"73","author":"Guglin","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pellikka, P.A., She, L., Holly, T.A., Lin, G., Varadarajan, P., Pai, R.G., Bonow, R.O., Pohost, G.M., Panza, J.A., and Berman, D.S. (2018). Variability in ejection fraction measured by echocardiography, gated single-photon emission computed tomography, and cardiac magnetic resonance in patients with coronary artery disease and left ventricular dysfunction. JAMA Network Open, 1.","DOI":"10.1001\/jamanetworkopen.2018.1456"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/CCO.0000000000000492","article-title":"Escalation and de-escalation in HER2 positive early breast cancer","volume":"31","author":"Dieci","year":"2019","journal-title":"Curr. Opin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/2\/327\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:53:25Z","timestamp":1760172805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/2\/327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,31]]},"references-count":19,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["cancers12020327"],"URL":"https:\/\/doi.org\/10.3390\/cancers12020327","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,31]]}}}