{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:10:54Z","timestamp":1790799054947,"version":"4.1.0"},"reference-count":37,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2017,3,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>The primary toxicity of trastuzumab therapy for human epidermal growth factor receptor 2\u2013overexpressing (HER2-positive) breast cancer is dose-independent cardiac dysfunction. Angiotensin-converting enzyme inhibitors and \u03b2-blockers are recommended first-line agents for heart failure. We hypothesized that angiotensin-converting enzyme inhibitors and \u03b2-blockers could prevent trastuzumab-related cardiotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>In this double-blinded, placebo-controlled trial, patients with HER2-positive early breast cancer were randomly assigned to receive treatment with perindopril, bisoprolol, or placebo (1:1:1) for the duration of trastuzumab adjuvant therapy. Patients underwent cardiac magnetic resonance imaging at baseline and post\u2013cycle 17 for the determination of left ventricular volumes and left ventricular ejection fraction (LVEF). Cardiotoxicity was evaluated as the change in indexed left ventricular end diastolic volume and LVEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty-three patients received perindopril, 31 received bisoprolol, and 30 received placebo. Baseline demographic, cancer, and cardiovascular profiles were similar between groups. Study drugs were well tolerated with no serious adverse events. After 17 cycles of trastuzumab, indexed left ventricular end diastolic volume increased in patients treated with perindopril (+7 \u00b1 14 mL\/m\n                      <jats:sup>2<\/jats:sup>\n                      ), bisoprolol (+8 mL \u00b1 9 mL\/m\n                      <jats:sup>2<\/jats:sup>\n                      ), and placebo (+4 \u00b1 11 mL\/m\n                      <jats:sup>2<\/jats:sup>\n                      ; P = .36). In secondary analyses, trastuzumab-mediated decline in LVEF was attenuated in bisoprolol-treated patients (\u22121 \u00b1 5%) relative to the perindopril (\u22123 \u00b1 4%) and placebo (\u22125 \u00b1 5%) groups ( P = .001). Perindopril and bisoprolol use were independent predictors of maintained LVEF on multivariable analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Perindopril and bisoprolol were well tolerated in patients with HER2-positive early breast cancer who received trastuzumab and protected against cancer therapy\u2013related declines in LVEF; however, trastuzumab-mediated left ventricular remodeling\u2014the primary outcome\u2014was not prevented by these pharmacotherapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.2016.68.7830","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T12:11:27Z","timestamp":1487851887000},"page":"870-877","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":342,"title":["Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101\u2013Breast): A Randomized Trial for the Prevention of Trastuzumab-Associated Cardiotoxicity"],"prefix":"10.1200","volume":"35","author":[{"given":"Edith","family":"Pituskin","sequence":"first","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. Ezekowitz, and D. Ian Paterson, University of Alberta, Edmonton, Alberta; and Davinder Jassal and Marshall Pitz, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Mackey","sequence":"additional","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. Ezekowitz, and D. Ian Paterson, University of Alberta, Edmonton, Alberta; and Davinder Jassal and Marshall Pitz, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheri","family":"Koshman","sequence":"additional","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. Ezekowitz, and D. Ian Paterson, University of Alberta, Edmonton, Alberta; and Davinder Jassal and Marshall Pitz, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davinder","family":"Jassal","sequence":"additional","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. Ezekowitz, and D. Ian Paterson, University of Alberta, Edmonton, Alberta; and Davinder Jassal and Marshall Pitz, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall","family":"Pitz","sequence":"additional","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. Ezekowitz, and D. Ian Paterson, University of Alberta, Edmonton, Alberta; and Davinder Jassal and Marshall Pitz, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Haykowsky","sequence":"additional","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. Ezekowitz, and D. Ian Paterson, University of Alberta, Edmonton, Alberta; and Davinder Jassal and Marshall Pitz, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J.","family":"Pagano","sequence":"additional","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. Ezekowitz, and D. Ian Paterson, University of Alberta, Edmonton, Alberta; and Davinder Jassal and Marshall Pitz, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin","family":"Chow","sequence":"additional","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. Ezekowitz, and D. Ian Paterson, University of Alberta, Edmonton, Alberta; and Davinder Jassal and Marshall Pitz, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. Ezekowitz, and D. Ian Paterson, University of Alberta, Edmonton, Alberta; and Davinder Jassal and Marshall Pitz, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa J.","family":"Vos","sequence":"additional","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. Ezekowitz, and D. Ian Paterson, University of Alberta, Edmonton, Alberta; and Davinder Jassal and Marshall Pitz, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Edith Pituskin John R. Mackey, Sheri Koshman, Mark J. Haykowsky, Joseph J. Pagano, Kelvin Chow, Richard B. Thompson, Larissa J. Vos, Sunita Ghosh, Gavin Y. Oudit, Justin A. 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