Anthony F Yu1, Alice Y Ho2, Lior Z Braunstein3, Maria E Thor4, Katherine Lee Chuy5, Anne Eaton6, Elton Mara5, Oren Cahlon3, Chau T Dang7, Kevin C Oeffinger8, Richard M Steingart9, Jennifer E Liu9. 1. Cardiology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. Electronic address: yua3@mskcc.org. 2. Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. 3. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. 4. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Cardiology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 6. Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota. 7. Weill Cornell Medical College, New York, New York; Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 8. Department of Medicine, Duke Cancer Institute, Durham, NC. 9. Cardiology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
Abstract
BACKGROUND: Radiation therapy (RT)-induced cardiotoxicity is among the concerning sequelae of breast cancer (BCA) treatment, particularly in HER2-positive BCA patients who receive anthracyclines and trastuzumab-based therapy. The aim of this study was to assess for early RT-induced changes in echocardiographic and circulating biomarkers of left ventricular (LV) function and evaluate their association with radiation dose to the heart among patients with HER2-positive BCA treated with contemporary RT. METHODS: A total of 47 women with HER2-positive BCA who were treated with an anthracycline, trastuzumab, and RT to the breast and/or chest wall ± regional lymph nodes were included in this study. Two-dimensional echocardiography with speckle-tracking imaging was performed at baseline (prechemotherapy), prior to and after RT (pre-RT and post-RT), and 6 months post-RT. High-sensitivity troponin I (hsTnI) was measured pre-RT and post-RT. Associations between mean heart dose (MHD) and changes in LV function after RT were examined in multivariable linear regression models. RESULTS: The MHD was 1.8 ± 1.5 Gy for patients receiving left-sided RT (n = 26) and 1.1 ± 1.3 Gy for patients receiving right-sided RT (n = 21). Pre-RT, post-RT, and 6-month post-RT echocardiograms were performed at median (interquartile range) of 49 days (27, 77) before and 54 days (25, 78) and 195 days (175, 226) after RT, respectively. Compared with pre-RT, a minimal decrease in LV ejection fraction was observed post-RT (61% ± 7% vs 59% ± 8%; P = .003) without any significant change in global longitudinal, circumferential, or radial strain or diastolic indices at the post-RT timepoint. Median (interquartile range) concentrations of hsTnI decreased from 5.7 pg/mL (3.0, 8.7) pre-RT to 3.7 pg/mL (2.0, 5.9) post-RT. There was no significant change in systolic or diastolic indices of LV function at 6 months post-RT compared with pre-RT. MHD was not associated with changes in echocardiographic parameters of LV function after RT. CONCLUSIONS: Breast RT using contemporary techniques can be delivered without evidence of early subclinical LV dysfunction or injury as measured by echocardiography and hsTnI in patients treated with anthracyclines and trastuzumab. Future studies should focus on identifying alternative biomarkers to elucidate early RT-induced cardiovascular effects and further characterizing long-term cardiovascular outcomes associated with contemporary breast RT.
BACKGROUND: Radiation therapy (RT)-induced cardiotoxicity is among the concerning sequelae of breast cancer (BCA) treatment, particularly in HER2-positive BCA patients who receive anthracyclines and trastuzumab-based therapy. The aim of this study was to assess for early RT-induced changes in echocardiographic and circulating biomarkers of left ventricular (LV) function and evaluate their association with radiation dose to the heart among patients with HER2-positive BCA treated with contemporary RT. METHODS: A total of 47 women with HER2-positive BCA who were treated with an anthracycline, trastuzumab, and RT to the breast and/or chest wall ± regional lymph nodes were included in this study. Two-dimensional echocardiography with speckle-tracking imaging was performed at baseline (prechemotherapy), prior to and after RT (pre-RT and post-RT), and 6 months post-RT. High-sensitivity troponin I (hsTnI) was measured pre-RT and post-RT. Associations between mean heart dose (MHD) and changes in LV function after RT were examined in multivariable linear regression models. RESULTS: The MHD was 1.8 ± 1.5 Gy for patients receiving left-sided RT (n = 26) and 1.1 ± 1.3 Gy for patients receiving right-sided RT (n = 21). Pre-RT, post-RT, and 6-month post-RT echocardiograms were performed at median (interquartile range) of 49 days (27, 77) before and 54 days (25, 78) and 195 days (175, 226) after RT, respectively. Compared with pre-RT, a minimal decrease in LV ejection fraction was observed post-RT (61% ± 7% vs 59% ± 8%; P = .003) without any significant change in global longitudinal, circumferential, or radial strain or diastolic indices at the post-RT timepoint. Median (interquartile range) concentrations of hsTnI decreased from 5.7 pg/mL (3.0, 8.7) pre-RT to 3.7 pg/mL (2.0, 5.9) post-RT. There was no significant change in systolic or diastolic indices of LV function at 6 months post-RT compared with pre-RT. MHD was not associated with changes in echocardiographic parameters of LV function after RT. CONCLUSIONS: Breast RT using contemporary techniques can be delivered without evidence of early subclinical LV dysfunction or injury as measured by echocardiography and hsTnI in patients treated with anthracyclines and trastuzumab. Future studies should focus on identifying alternative biomarkers to elucidate early RT-induced cardiovascular effects and further characterizing long-term cardiovascular outcomes associated with contemporary breast RT.
Authors: Editha A Krueger; Benedick A Fraass; Daniel L McShan; Robin Marsh; Lori J Pierce Journal: Int J Radiat Oncol Biol Phys Date: 2003-07-15 Impact factor: 7.038
Authors: Mary Feng; Jean M Moran; Todd Koelling; Aamer Chughtai; June L Chan; Laura Freedman; James A Hayman; Reshma Jagsi; Shruti Jolly; Janice Larouere; Julie Soriano; Robin Marsh; Lori J Pierce Journal: Int J Radiat Oncol Biol Phys Date: 2010-04-24 Impact factor: 7.038
Authors: Lawrence B Marks; Xiaoli Yu; Robert G Prosnitz; Su-Min Zhou; Patricia H Hardenbergh; Michael Blazing; Donna Hollis; Pehr Lind; Andrea Tisch; Terence Z Wong; Salvador Borges-Neto Journal: Int J Radiat Oncol Biol Phys Date: 2005-09-01 Impact factor: 7.038
Authors: Roberto M Lang; Michelle Bierig; Richard B Devereux; Frank A Flachskampf; Elyse Foster; Patricia A Pellikka; Michael H Picard; Mary J Roman; James Seward; Jack S Shanewise; Scott D Solomon; Kirk T Spencer; Martin St John Sutton; William J Stewart Journal: J Am Soc Echocardiogr Date: 2005-12 Impact factor: 5.251
Authors: M Clarke; R Collins; S Darby; C Davies; P Elphinstone; V Evans; J Godwin; R Gray; C Hicks; S James; E MacKinnon; P McGale; T McHugh; R Peto; C Taylor; Y Wang Journal: Lancet Date: 2005-12-17 Impact factor: 79.321
Authors: Joseph Ragaz; Ivo A Olivotto; John J Spinelli; Norman Phillips; Stewart M Jackson; Kenneth S Wilson; Margaret A Knowling; Christopher M L Coppin; Lorna Weir; Karen Gelmon; Nhu Le; Ralph Durand; Andrew J Coldman; Mohamed Manji Journal: J Natl Cancer Inst Date: 2005-01-19 Impact factor: 13.506
Authors: Carmen C Popescu; Ivo A Olivotto; Wayne A Beckham; Will Ansbacher; Sergei Zavgorodni; Richard Shaffer; Elaine S Wai; Karl Otto Journal: Int J Radiat Oncol Biol Phys Date: 2010-01-01 Impact factor: 7.038
Authors: Paul A Heidenreich; Steven L Hancock; Byron K Lee; Carol S Mariscal; Ingela Schnittger Journal: J Am Coll Cardiol Date: 2003-08-20 Impact factor: 24.094
Authors: Lee W Jones; Mark J Haykowsky; Jonas J Swartz; Pamela S Douglas; John R Mackey Journal: J Am Coll Cardiol Date: 2007-09-24 Impact factor: 24.094
Authors: Carmen Bergom; Jason Rubenstein; J Frank Wilson; Aimee Welsh; El-Sayed H Ibrahim; Phillip Prior; Aronne M Schottstaedt; Daniel Eastwood; Mei-Jie Zhang; Adam Currey; Lindsay Puckett; Jennifer L Strande; Julie A Bradley; Julia White Journal: Front Oncol Date: 2020-10-16 Impact factor: 6.244