[Skip to Content]
[Skip to Content Landing]

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
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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

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.

References
1.
Gilchrist  SC , Barac  A , Ades  PA ,  et al; American Heart Association Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and Council on Peripheral Vascular Disease.  Cardio-oncology rehabilitation to manage cardiovascular outcomes in cancer patients and survivors: a scientific statement from the American Heart Association.   Circulation. 2019;139(21):e997-e1012. doi:10.1161/CIR.0000000000000679 PubMedGoogle ScholarCrossref
2.
Stoltzfus  KC , Zhang  Y , Sturgeon  K ,  et al.  Fatal heart disease among cancer patients.   Nat Commun. 2020;11(1):2011. doi:10.1038/s41467-020-15639-5 PubMedGoogle ScholarCrossref
3.
Virani  SS , Alonso  A , Benjamin  EJ ,  et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.  Heart disease and stroke statistics-2020 update: a report from the American Heart Association.   Circulation. 2020;141(9):e139-e596. doi:10.1161/CIR.0000000000000757 PubMedGoogle ScholarCrossref
4.
Curigliano  G , Lenihan  D , Fradley  M ,  et al; ESMO Guidelines Committee.  Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.   Ann Oncol. 2020;31(2):171-190. doi:10.1016/j.annonc.2019.10.023 PubMedGoogle ScholarCrossref
5.
Cardinale  D , Colombo  A , Bacchiani  G ,  et al.  Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy.   Circulation. 2015;131(22):1981-1988. doi:10.1161/CIRCULATIONAHA.114.013777 PubMedGoogle ScholarCrossref
6.
Slamon  D , Eiermann  W , Robert  N ,  et al; Breast Cancer International Research Group.  Adjuvant trastuzumab in HER2-positive breast cancer.   N Engl J Med. 2011;365(14):1273-1283. doi:10.1056/NEJMoa0910383 PubMedGoogle ScholarCrossref
7.
Cuzick  J , Stewart  H , Rutqvist  L ,  et al.  Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy.   J Clin Oncol. 1994;12(3):447-453. doi:10.1200/JCO.1994.12.3.447 PubMedGoogle ScholarCrossref
8.
Clarke  M , Collins  R , Darby  S ,  et al; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).  Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.   Lancet. 2005;366(9503):2087-2106. doi:10.1016/S0140-6736(05)67887-7 PubMedGoogle ScholarCrossref
9.
Darby  S , McGale  P , Correa  C ,  et al; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).  Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials.   Lancet. 2011;378(9804):1707-1716. doi:10.1016/S0140-6736(11)61629-2 PubMedGoogle ScholarCrossref
10.
Aznar  MC , Korreman  SS , Pedersen  AN , Persson  GF , Josipovic  M , Specht  L .  Evaluation of dose to cardiac structures during breast irradiation.   Br J Radiol. 2011;84(1004):743-746. doi:10.1259/bjr/12497075 PubMedGoogle ScholarCrossref
11.
Darby  SC , Ewertz  M , McGale  P ,  et al.  Risk of ischemic heart disease in women after radiotherapy for breast cancer.   N Engl J Med. 2013;368(11):987-998. doi:10.1056/NEJMoa1209825 PubMedGoogle ScholarCrossref
12.
Zhao  W , Robbins  ME .  Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications.   Curr Med Chem. 2009;16(2):130-143. doi:10.2174/092986709787002790 PubMedGoogle ScholarCrossref
13.
Baselet  B , Rombouts  C , Benotmane  AM , Baatout  S , Aerts  A .  Cardiovascular diseases related to ionizing radiation: the risk of low-dose exposure (review).   Int J Mol Med. 2016;38(6):1623-1641. doi:10.3892/ijmm.2016.2777 PubMedGoogle ScholarCrossref
14.
Wang  H , Wei  J , Zheng  Q ,  et al.  Radiation-induced heart disease: a review of classification, mechanism and prevention.   Int J Biol Sci. 2019;15(10):2128-2138. doi:10.7150/ijbs.35460 PubMedGoogle ScholarCrossref
15.
Yamamori  T , Yasui  H , Yamazumi  M ,  et al.  Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and mitochondrial content under control of the cell cycle checkpoint.   Free Radic Biol Med. 2012;53(2):260-270. doi:10.1016/j.freeradbiomed.2012.04.033 PubMedGoogle ScholarCrossref
16.
Viczenczova  C , Kura  B , Egan Benova  T ,  et al.  Irradiation-induced cardiac connexin-43 and miR-21 responses are hampered by treatment with atorvastatin and aspirin.   Int J Mol Sci. 2018;19(4):E1128. doi:10.3390/ijms19041128 PubMedGoogle Scholar
17.
Gagliardi  G , Constine  LS , Moiseenko  V ,  et al.  Radiation dose-volume effects in the heart.   Int J Radiat Oncol Biol Phys. 2010;76(3 suppl):S77-S85. doi:10.1016/j.ijrobp.2009.04.093 PubMedGoogle ScholarCrossref
18.
Darby  SC , Cutter  DJ , Boerma  M ,  et al.  Radiation-related heart disease: current knowledge and future prospects.   Int J Radiat Oncol Biol Phys. 2010;76(3):656-665. doi:10.1016/j.ijrobp.2009.09.064 PubMedGoogle ScholarCrossref
19.
Larsen  RL , Jakacki  RI , Vetter  VL , Meadows  AT , Silber  JH , Barber  G .  Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults.   Am J Cardiol. 1992;70(1):73-77. doi:10.1016/0002-9149(92)91393-I PubMedGoogle ScholarCrossref
20.
Carlson  RG , Mayfield  WR , Normann  S , Alexander  JA .  Radiation-associated valvular disease.   Chest. 1991;99(3):538-545. doi:10.1378/chest.99.3.538 PubMedGoogle ScholarCrossref
21.
Zaorsky  NG , Zhang  Y , Tchelebi  LT , Mackley  HB , Chinchilli  VM , Zacharia  BE .  Stroke among cancer patients.   Nat Commun. 2019;10(1):5172. doi:10.1038/s41467-019-13120-6 PubMedGoogle ScholarCrossref
22.
Jacob  S , Pathak  A , Franck  D ,  et al.  Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study.   Radiat Oncol. 2016;11:54. doi:10.1186/s13014-016-0627-5 PubMedGoogle ScholarCrossref
23.
Yu  AF , Ho  AY , Braunstein  LZ ,  et al.  Assessment of early radiation-induced changes in left ventricular function by myocardial strain imaging after breast radiation therapy.   J Am Soc Echocardiogr. 2019;32(4):521-528. doi:10.1016/j.echo.2018.12.009 PubMedGoogle ScholarCrossref
24.
Milgrom  SA , Varghese  B , Gladish  GW ,  et al.  Coronary artery dose-volume parameters predict risk of calcification after radiation therapy.   J Cardiovasc Imaging. 2019;27(4):268-279. doi:10.4250/jcvi.2019.27.e38 PubMedGoogle ScholarCrossref
25.
Karamitsos  TD , Arvanitaki  A , Karvounis  H , Neubauer  S , Ferreira  VM .  Myocardial tissue characterization and fibrosis by imaging.   JACC Cardiovasc Imaging. 2020;13(5):1221-1234. doi:10.1016/j.jcmg.2019.06.030 PubMedGoogle ScholarCrossref
26.
Skyttä  T , Tuohinen  S , Boman  E , Virtanen  V , Raatikainen  P , Kellokumpu-Lehtinen  PL .  Troponin T-release associates with cardiac radiation doses during adjuvant left-sided breast cancer radiotherapy.   Radiat Oncol. 2015;10:141. doi:10.1186/s13014-015-0436-2 PubMedGoogle ScholarCrossref
27.
D’Errico  MP , Grimaldi  L , Petruzzelli  MF ,  et al.  N-terminal pro-B-type natriuretic peptide plasma levels as a potential biomarker for cardiac damage after radiotherapy in patients with left-sided breast cancer.   Int J Radiat Oncol Biol Phys. 2012;82(2):e239-e246. doi:10.1016/j.ijrobp.2011.03.058 PubMedGoogle ScholarCrossref
28.
Aula  H , Skyttä  T , Tuohinen  S ,  et al.  ST2 levels increased and were associated with changes in left ventricular systolic function during a three-year follow-up after adjuvant radiotherapy for breast cancer.   Breast. 2020;49:183-186. doi:10.1016/j.breast.2019.12.001 PubMedGoogle ScholarCrossref
29.
Rutqvist  LE , Lax  I , Fornander  T , Johansson  H .  Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer.   Int J Radiat Oncol Biol Phys. 1992;22(5):887-896. doi:10.1016/0360-3016(92)90784-F PubMedGoogle ScholarCrossref
30.
Valagussa  P , Zambetti  M , Biasi  S , Moliterni  A , Zucali  R , Bonadonna  G .  Cardiac effects following adjuvant chemotherapy and breast irradiation in operable breast cancer.   Ann Oncol. 1994;5(3):209-216. doi:10.1093/oxfordjournals.annonc.a058795 PubMedGoogle ScholarCrossref
31.
Houghton  J , Baum  M , Haybittle  JL ; The Closed Trials Working Party of the CRC Breast Cancer Trials Group.  Role of radiotherapy following total mastectomy in patients with early breast cancer.   World J Surg. 1994;18(1):117-122. doi:10.1007/BF00348201 PubMedGoogle ScholarCrossref
32.
Højris  I , Overgaard  M , Christensen  JJ , Overgaard  J ; Radiotherapy Committee of the Danish Breast Cancer Cooperative Group.  Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials.   Lancet. 1999;354(9188):1425-1430. doi:10.1016/S0140-6736(99)02245-X PubMedGoogle ScholarCrossref
33.
Woodward  WA , Strom  EA , McNeese  MD ,  et al.  Cardiovascular death and second non-breast cancer malignancy after postmastectomy radiation and doxorubicin-based chemotherapy.   Int J Radiat Oncol Biol Phys. 2003;57(2):327-335. doi:10.1016/S0360-3016(03)00594-7PubMedGoogle ScholarCrossref
34.
Halyard  MY , Pisansky  TM , Dueck  AC ,  et al.  Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG phase III Trial N9831.   J Clin Oncol. 2009;27(16):2638-2644. doi:10.1200/JCO.2008.17.9549 PubMedGoogle ScholarCrossref
35.
Killander  F , Anderson  H , Kjellén  E , Malmström  P .  Increased cardio and cerebrovascular mortality in breast cancer patients treated with postmastectomy radiotherapy--25 year follow-up of a randomised trial from the South Sweden Breast Cancer Group.   Eur J Cancer. 2014;50(13):2201-2210. doi:10.1016/j.ejca.2014.04.033 PubMedGoogle ScholarCrossref
36.
Hennequin  C , Bossard  N , Servagi-Vernat  S ,  et al.  Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy.   Int J Radiat Oncol Biol Phys. 2013;86(5):860-866. doi:10.1016/j.ijrobp.2013.03.021 PubMedGoogle ScholarCrossref
37.
Poortmans  PM , Collette  S , Kirkove  C ,  et al; EORTC Radiation Oncology and Breast Cancer Groups.  Internal mammary and medial supraclavicular irradiation in breast cancer.   N Engl J Med. 2015;373(4):317-327. doi:10.1056/NEJMoa1415369 PubMedGoogle ScholarCrossref
38.
Whelan  TJ , Olivotto  IA , Parulekar  WR ,  et al; MA.20 Study Investigators.  Regional nodal irradiation in early-stage breast cancer.   N Engl J Med. 2015;373(4):307-316. doi:10.1056/NEJMoa1415340 PubMedGoogle ScholarCrossref
39.
Jacob  S , Camilleri  J , Derreumaux  S ,  et al.  Is mean heart dose a relevant surrogate parameter of left ventricle and coronary arteries exposure during breast cancer radiotherapy: a dosimetric evaluation based on individually-determined radiation dose (BACCARAT study).   Radiat Oncol. 2019;14(1):29. doi:10.1186/s13014-019-1234-z PubMedGoogle ScholarCrossref
40.
Taylor  C , Correa  C , Duane  FK ,  et al; Early Breast Cancer Trialists’ Collaborative Group.  Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials.   J Clin Oncol. 2017;35(15):1641-1649. doi:10.1200/JCO.2016.72.0722 PubMedGoogle ScholarCrossref
41.
van den Bogaard  VA , Ta  BD , van der Schaaf  A ,  et al.  Validation and modification of a prediction model for acute cardiac events in patients with breast cancer treated with radiotherapy based on three-dimensional dose distributions to cardiac substructures.   J Clin Oncol. 2017;35(11):1171-1178. doi:10.1200/JCO.2016.69.8480 PubMedGoogle ScholarCrossref
42.
Trott  KR , Doerr  W , Facoetti  A ,  et al.  Biological mechanisms of normal tissue damage: importance for the design of NTCP models.   Radiother Oncol. 2012;105(1):79-85. doi:10.1016/j.radonc.2012.05.008 PubMedGoogle ScholarCrossref
43.
Pierce  LJ , Feng  M , Griffith  KA ,  et al; Michigan Radiation Oncology Quality Consortium.  Recent time trends and predictors of heart dose from breast radiation therapy in a large quality consortium of radiation oncology practices.   Int J Radiat Oncol Biol Phys. 2017;99(5):1154-1161. doi:10.1016/j.ijrobp.2017.07.022 PubMedGoogle ScholarCrossref
44.
Lohr  F , El-Haddad  M , Dobler  B ,  et al.  Potential effect of robust and simple IMRT approach for left-sided breast cancer on cardiac mortality.   Int J Radiat Oncol Biol Phys. 2009;74(1):73-80. doi:10.1016/j.ijrobp.2008.07.018 PubMedGoogle ScholarCrossref
45.
Balaji  K , Balaji Subramanian  S , Sathiya  K , Thirunavukarasu  M , Anu Radha  C , Ramasubramanian  V .  Hybrid planning techniques for hypofractionated whole-breast irradiation using flattening filter-free beams.   Strahlenther Onkol. 2020;196(4):376-385. doi:10.1007/s00066-019-01555-1 PubMedGoogle ScholarCrossref
46.
Pignol  JP , Olivotto  I , Rakovitch  E ,  et al.  A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis.   J Clin Oncol. 2008;26(13):2085-2092. doi:10.1200/JCO.2007.15.2488 PubMedGoogle ScholarCrossref
47.
Mukesh  MB , Barnett  GC , Wilkinson  JS ,  et al.  Randomized controlled trial of intensity-modulated radiotherapy for early breast cancer: 5-year results confirm superior overall cosmesis.   J Clin Oncol. 2013;31(36):4488-4495. doi:10.1200/JCO.2013.49.7842 PubMedGoogle ScholarCrossref
48.
Zhao  H , He  M , Cheng  G ,  et al.  A comparative dosimetric study of left sided breast cancer after breast-conserving surgery treated with VMAT and IMRT.   Radiat Oncol. 2015;10:231. doi:10.1186/s13014-015-0531-4 PubMedGoogle ScholarCrossref
49.
Haciislamoglu  E , Colak  F , Canyilmaz  E ,  et al.  Dosimetric comparison of left-sided whole-breast irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical tomotherapy, and volumetric arc therapy.   Phys Med. 2015;31(4):360-367. doi:10.1016/j.ejmp.2015.02.005 PubMedGoogle ScholarCrossref
50.
Jin  GH , Chen  LX , Deng  XW , Liu  XW , Huang  Y , Huang  XB .  A comparative dosimetric study for treating left-sided breast cancer for small breast size using five different radiotherapy techniques: conventional tangential field, filed-in-filed, tangential-IMRT, multi-beam IMRT and VMAT.   Radiat Oncol. 2013;8:89. doi:10.1186/1748-717X-8-89 PubMedGoogle ScholarCrossref
51.
Duane  FK , McGale  P , Teoh  S ,  et al.  International variation in criteria for internal mammary chain radiotherapy.   Clin Oncol (R Coll Radiol). 2019;31(7):453-461. doi:10.1016/j.clon.2019.04.007 PubMedGoogle ScholarCrossref
52.
Taylor  CW , Wang  Z , Macaulay  E , Jagsi  R , Duane  F , Darby  SC .  Exposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003 to 2013.   Int J Radiat Oncol Biol Phys. 2015;93(4):845-853. doi:10.1016/j.ijrobp.2015.07.2292 PubMedGoogle ScholarCrossref
53.
Murray Brunt  A , Haviland  JS , Wheatley  DA ,  et al; FAST-Forward Trial Management Group.  Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial.   Lancet. 2020;395(10237):1613-1626. doi:10.1016/S0140-6736(20)30932-6 PubMedGoogle ScholarCrossref
54.
Poortmans  PMP , Takanen  S , Marta  GN , Meattini  I , Kaidar-Person  O .  Winter is over: the use of artificial intelligence to individualise radiation therapy for breast cancer.   Breast. 2020;49:194-200. doi:10.1016/j.breast.2019.11.011 PubMedGoogle ScholarCrossref
55.
Aznar  MC , Duane  FK , Darby  SC , Wang  Z , Taylor  CW .  Exposure of the lungs in breast cancer radiotherapy: a systematic review of lung doses published 2010-2015.   Radiother Oncol. 2018;126(1):148-154. doi:10.1016/j.radonc.2017.11.022 PubMedGoogle ScholarCrossref
56.
Nissen  HD , Appelt  AL .  Improved heart, lung and target dose with deep inspiration breath hold in a large clinical series of breast cancer patients.   Radiother Oncol. 2013;106(1):28-32. doi:10.1016/j.radonc.2012.10.016 PubMedGoogle ScholarCrossref
57.
Lakosi  F , Gulyban  A , Simoni  SB ,  et al.  The influence of treatment position (prone vs. supine) on clip displacement, seroma, tumor bed and partial breast target volumes: comparative study.   Pathol Oncol Res. 2016;22(3):493-500. doi:10.1007/s12253-015-0028-3 PubMedGoogle ScholarCrossref
58.
Rodgers  B , Jaroszewski  DE , Ashman  JB , Rule  WG , Sio  TT , Keole  SR .  Advantages of post-mastectomy proton beam therapy in a breast cancer patient with pectus excavatum.   J Med Cases. 2017;8(3):98-101. doi:10.14740/jmc2781w Google ScholarCrossref
59.
DeCesaris  CM , Rice  SR , Bentzen  SM , Jatczak  J , Mishra  MV , Nichols  EM .  Quantification of acute skin toxicities in patients with breast cancer undergoing adjuvant proton versus photon radiation therapy: a single institutional experience.   Int J Radiat Oncol Biol Phys. 2019;104(5):1084-1090. doi:10.1016/j.ijrobp.2019.04.015 PubMedGoogle ScholarCrossref
60.
Galland-Girodet  S , Pashtan  I , MacDonald  SM ,  et al.  Long-term cosmetic outcomes and toxicities of proton beam therapy compared with photon-based 3-dimensional conformal accelerated partial-breast irradiation: a phase 1 trial.   Int J Radiat Oncol Biol Phys. 2014;90(3):493-500. doi:10.1016/j.ijrobp.2014.04.008 PubMedGoogle ScholarCrossref
61.
Appelt  AL , Vogelius  IR , Bentzen  SM .  Modern hypofractionation schedules for tangential whole breast irradiation decrease the fraction size-corrected dose to the heart.   Clin Oncol (R Coll Radiol). 2013;25(3):147-152. doi:10.1016/j.clon.2012.07.012 PubMedGoogle ScholarCrossref
62.
Haviland  JS , Owen  JR , Dewar  JA ,  et al; START Trialists’ Group.  The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials.   Lancet Oncol. 2013;14(11):1086-1094. doi:10.1016/S1470-2045(13)70386-3PubMedGoogle ScholarCrossref
63.
Whelan  TJ , Pignol  JP , Levine  MN ,  et al.  Long-term results of hypofractionated radiation therapy for breast cancer.   N Engl J Med. 2010;362(6):513-520. doi:10.1056/NEJMoa0906260 PubMedGoogle ScholarCrossref
64.
Poortmans  P , Kaidar-Person  O , Span  P .  Radiation oncology enters the era of individualised medicine.   Lancet Oncol. 2017;18(2):159-160. doi:10.1016/S1470-2045(16)30660-X PubMedGoogle ScholarCrossref
65.
Hughes  KS , Schnaper  LA , Bellon  JR ,  et al.  Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343.   J Clin Oncol. 2013;31(19):2382-2387. doi:10.1200/JCO.2012.45.2615 PubMedGoogle ScholarCrossref
66.
Whelan  T , Levine  M , Sussman  J .  Hypofractionated breast irradiation: what’s next?   J Clin Oncol. 2020;38(28):3245-3247. doi:10.1200/JCO.20.01243 PubMedGoogle ScholarCrossref
67.
Vicini  FA , Cecchini  RS , White  JR ,  et al.  Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial.   Lancet. 2019;394(10215):2155-2164. doi:10.1016/S0140-6736(19)32514-0 PubMedGoogle ScholarCrossref
68.
Strnad  V , Ott  OJ , Hildebrandt  G ,  et al; Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO).  5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial.   Lancet. 2016;387(10015):229-238. doi:10.1016/S0140-6736(15)00471-7 PubMedGoogle ScholarCrossref
69.
Coles  CE , Griffin  CL , Kirby  AM ,  et al; IMPORT Trialists.  Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial.   Lancet. 2017;390(10099):1048-1060. doi:10.1016/S0140-6736(17)31145-5 PubMedGoogle ScholarCrossref
70.
Meattini  I , Marrazzo  L , Saieva  C ,  et al.  Accelerated partial-breast irradiation compared with whole-breast irradiation for early breast cancer: long-term results of the randomized phase III APBI-IMRT-Florence Trial.   J Clin Oncol. 2020;38(35):4175-4183. doi:10.1200/JCO.20.00650 PubMedGoogle ScholarCrossref
71.
Kaidar-Person  O , Meattini  I , Zippel  D , Poortmans  P .  Apples and oranges: comparing partial breast irradiation techniques.   Rep Pract Oncol Radiother. 2020;25(5):780-782. doi:10.1016/j.rpor.2020.07.008 PubMedGoogle ScholarCrossref
72.
Zhang  K , He  X , Zhou  Y ,  et al.  Atorvastatin ameliorates radiation-induced cardiac fibrosis in rats.   Radiat Res. 2015;184(6):611-620. doi:10.1667/RR14075.1 PubMedGoogle ScholarCrossref
73.
van der Veen  SJ , Ghobadi  G , de Boer  RA ,  et al.  ACE inhibition attenuates radiation-induced cardiopulmonary damage.   Radiother Oncol. 2015;114(1):96-103. doi:10.1016/j.radonc.2014.11.017 PubMedGoogle ScholarCrossref
74.
Yu  JM , Hsieh  MC , Qin  L , Zhang  J , Wu  SY .  Metformin reduces radiation-induced cardiac toxicity risk in patients having breast cancer.   Am J Cancer Res. 2019;9(5):1017-1026.PubMedGoogle Scholar
75.
Du  S , Zhou  L , Alexander  GS ,  et al.  PD-1 modulates radiation-induced cardiac toxicity through cytotoxic T lymphocytes.   J Thorac Oncol. 2018;13(4):510-520. doi:10.1016/j.jtho.2017.12.002 PubMedGoogle ScholarCrossref
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 [and Self-Assessment requirements] 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.

Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close