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Breast Cancer

Association of Breast Cancer Irradiation With Cardiac Toxic EffectsA Narrative Review

Educational Objective
To learn the cardiotoxic risk factors associated with breast cancer irradiation and strategies for mitigation.

1 Credit CME

JAMA Oncology

Published Online: March 4, 2021

Review

Article Information and Disclosures

Icro Meattini, MD^1,2;

Philip M. Poortmans, MD, PhD^3,4;

Marianne Camille Aznar, PhD^5,6;

Carlotta Becherini, MD²;

Elisabetta Bonzano, MD^7,8;

Daniela Cardinale, MD, PhD⁹;

Daniel J. Lenihan, MD¹⁰;

Livia Marrazzo, MSc¹¹;

Giuseppe Curigliano, MD, PhD^12,13;

Lorenzo Livi, MD^1,2

Author Affiliations

¹Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Florence, Italy
²Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
³Department of Radiation Oncology, Iridium Kankernetwerk, Wilrijk-Antwerp, Belgium
⁴University of Antwerp, Faculty of Medicine and Health Sciences, Wilrijk-Antwerp, Belgium
⁵Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, The Christie NHS Foundation Trust, Manchester, United Kingdom
⁶Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
⁷Department of Radiation Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Matteo Polyclinic Foundation, Pavia, Italy
⁸PhD School in Experimental Medicine, University of Pavia, Pavia, Italy
⁹Cardioncology Unit, European Institute of Oncology, IRCCS, Milan, Italy
¹⁰Cardio-Oncology Center of Excellence, Washington University in St Louis, St Louis, Missouri
¹¹Medical Physics Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
¹²Division of Early Drug Development, European Institute of Oncology, IRCCS, Milan, Italy
¹³Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

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Abstract

Importance To promptly recognize and manage cardiovascular (CV) risk factors before, during, and after cancer treatment, decreasing the risk of cancer therapy–related cardiac dysfunction is crucial. After recent advances in breast cancer treatment, mortality rates from cancer have decreased, and the prevalence of survivors with a potentially higher CV disease risk has increased. Cardiovascular risks might be associated with the multimodal approach, including systemic therapies and breast radiotherapy (RT).

Observations The heart disease risk seems to be higher in patients with tumors in the left breast, when other classic CV risk factors are present, and when adjunctive anthracycline-based chemotherapy is administered, suggesting a synergistic association. Respiratory control as well as modern RT techniques and their possible further refinement may decrease the prevalence and severity of radiation-induced heart disease. Several pharmacological cardioprevention strategies for decreasing cardiac toxic effects have been identified in several guidelines. However, further research is needed to ascertain the feasibility of these strategies in routine practice.

Conclusions and Relevance This review found that evidence-based recommendations are lacking on the modalities for and intensity of heart disease screening, surveillance of patients after RT, and treatment of these patients. A multidisciplinary and multimodal approach is crucial to guide optimal management.

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Article Information

Accepted for Publication: September 29, 2020.

Published Online: March 4, 2021. doi:10.1001/jamaoncol.2020.7468

Corresponding Author: Icro Meattini, MD, Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Viale Morgagni 50, 50134 Florence, Italy (icro.meattini@unifi.it).

Author Contributions: Dr Meattini had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Meattini and Poortmans contributed equally to the work.

Concept and design: Meattini, Poortmans, Cardinale, Lenihan, Marrazzo, Curigliano, Livi.

Acquisition, analysis, or interpretation of data: Meattini, Poortmans, Aznar, Becherini, Bonzano, Curigliano.

Drafting of the manuscript: Meattini, Poortmans, Aznar, Becherini, Bonzano, Cardinale, Marrazzo, Curigliano.

Critical revision of the manuscript for important intellectual content: Meattini, Poortmans, Aznar, Becherini, Cardinale, Lenihan, Marrazzo, Curigliano, Livi.

Administrative, technical, or material support: Meattini, Poortmans, Aznar, Becherini, Curigliano.

Supervision: Meattini, Poortmans, Cardinale, Lenihan, Curigliano, Livi.

Other - bibliographic research and manuscript writing, figures and tables: Marrazzo.

Other: Curigliano.

Conflict of Interest Disclosures: Dr Meattini reported serving on the advisory boards of Lilly, Pfizer, Roche, and Novartis outside the submitted work. Dr Poortmans reported being a medical advisor for Sordina IORT Technologies SpA. Dr Aznar reported receiving grants from the National Institute for Health Research Manchester Biomedical Research Centre and from the Cancer Research UK RadNet Manchester during the conduct of the study. Dr Lenihan reported receiving grants from Myocardial Solutions Inc outside the submitted work. Dr Marrazzo reported receiving financial support from Elekta to participate in the European Society for Radiotherapy and Oncology Congress. Dr Curigliano reported receiving grants from Merck and other from Roche, Novartis, Daiichi Sankyo, AstraZeneca, Lilly, Pfizer, Merck, BMS, and Ellipsis outside the submitted work. No other disclosures were reported.

Additional Contributions: Katherine Jones, MSc, The Christie NHS Foundation Trust; Giorgio Cartechini, MSc, University of Trento; and Marco Schwarz, MSc, PhD, Proton Therapy Center, provided permission to reprint the images in figures 2 and 3. These individuals received no additional compensation, outside of their usual salary, for their contributions.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.