Cardiovascular effects of breast cancer radiotherapy.

Cardiac toxicity has been implicated as the primary reason for excess non-breast cancer mortality in early breast cancer radiotherapy studies. Refinements in radiotherapy techniques have allowed for a considerable reduction of this risk in the majority of breast cancer patients. Recent large population-based studies confirmed an increase of cardiovascular death risk in patients irradiated for cancer of the left breast and in individuals exposed to relatively low (hitherto believed to be of no cardiovascular disease risk) doses of radiation, such as atomic bomb survivors or patients treated for various benign conditions. The issue of potential radiation-related cardiac damage may also be assuming a new significance due to the widespread use of other cardiotoxic agents, such as anthracyclines, paclitaxel and trastuzumab. The aim of this review is to summarize and critically analyze the available evidence on the impact of ionizing radiation on the cardiovascular system, with special attention to recent data demonstrating previously unrecognized adverse effects. This review discusses the pathology of radiation-related cardiovascular disease, its clinical presentation, risk factors and methods of assessment, as well as technical developments minimizing cardiac exposure. Epidemiological data are presented on the incidence of radiation-induced heart disease and cardiovascular mortality in various populations of patients irradiated for breast cancer and in individuals exposed to low radiation doses. Additionally, non-cardiac radiation-related vascular morbidity and mortality in breast cancer patients are addressed.

[1]  L. F. Fajardo The unique physiology of endothelial cells and its implications in radiobiology. , 1989, Frontiers of radiation therapy and oncology.

[2]  L. Marks,et al.  Is There an Increased Risk of Local Recurrence Under the Heart Block in Patients with Left‐Sided Breast Cancer? , 2004, Cancer journal.

[3]  Lawrence B Marks,et al.  Myocardial perfusion changes in patients irradiated for left-sided breast cancer and correlation with coronary artery distribution. , 2001, International journal of radiation oncology, biology, physics.

[4]  J. Wondergem,et al.  Changes in circulating atrial natriuretic peptide in relation to the cardiac status of Rhesus monkeys after total-body irradiation. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[5]  R. Jagsi,et al.  Stroke rates and risk factors in patients treated with radiation therapy for early-stage breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  C. Redmond,et al.  Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. , 1995, New England Journal of Medicine.

[7]  James S Goodwin,et al.  Risk of cardiac death after adjuvant radiotherapy for breast cancer. , 2005, Journal of the National Cancer Institute.

[8]  P. Canney,et al.  Reducing cardiac dose in post-operative irradiation of breast cancer patients: the relative importance of patient positioning and CT scan planning. , 1999, The British journal of radiology.

[9]  M. Overgaard,et al.  Myocardial perfusion imaging in breast cancer patients treated with or without post-mastectomy radiotherapy. , 2000, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[10]  R. Collins,et al.  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 , 2005, The Lancet.

[11]  W. Roberts,et al.  Radiation heart disease. Analysis of 16 young (aged 15 to 33 years) necropsy patients who received over 3,500 rads to the heart. , 1981, The American journal of medicine.

[12]  J. Overgaard,et al.  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 , 1999, The Lancet.

[13]  C. Easterly,et al.  Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications. , 2002, Medical physics.

[14]  M. Arnfield,et al.  Internal mammary node coverage: an investigation of presently accepted techniques. , 2000, International journal of radiation oncology, biology, physics.

[15]  M. Theodoulou,et al.  Cardiac effects of adjuvant therapy for early breast cancer. , 2003, Seminars in oncology.

[16]  M. Ikäheimo,et al.  Early cardiac changes related to radiation therapy. , 1985, The American journal of cardiology.

[17]  Mike Clarke,et al.  EFFECTS OF RADIOTHERAPY AND SURGERY IN EARLY BREAST-CANCER - AN OVERVIEW OF THE RANDOMIZED TRIALS , 1995 .

[18]  I. Lax,et al.  Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer. , 1992, International journal of radiation oncology, biology, physics.

[19]  J. Haybittle,et al.  Cardiac doses in post-operative breast irradiation. , 1992, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[20]  P. Douglas,et al.  Assessment of coronary heart disease morbidity and mortality after radiation therapy for early breast cancer. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  W. Woodward,et al.  Supraclavicular radiation for breast cancer does not increase the 10‐year risk of stroke , 2006, Cancer.

[22]  B. Mijnheer,et al.  Implementation of a forearm support to reduce the amount of irradiated lung and heart in radiation therapy of the breast. , 2001, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[23]  W. Mackillop,et al.  Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer: a population-based study in Ontario, Canada. , 1999, International journal of radiation oncology, biology, physics.

[24]  W. McCallion,et al.  Management of critical upper limb ischaemia long after irradiation injury of the subclavian and axillary arteries , 1991, The British journal of surgery.

[25]  P. Hall,et al.  Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90 000 Swedish women , 2003, BMJ : British Medical Journal.

[26]  G. Gagliardi,et al.  Early response of lung in breast cancer irradiation: radiologic density changes measured by CT and symptomatic radiation pneumonitis. , 2002, International journal of radiation oncology, biology, physics.

[27]  G. Matanoski,et al.  The current mortality rates of radiologists and other physician specialists: specific causes of death. , 1975, American journal of epidemiology.

[28]  I. Lax,et al.  Radiation therapy of stage I breast cancer: analysis of treatment technique accuracy using three-dimensional treatment planning tools. , 1992, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[29]  Ludvig Paul Muren,et al.  Cardiac and pulmonary doses and complication probabilities in standard and conformal tangential irradiation in conservative management of breast cancer. , 2002, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[30]  H. Bartelink,et al.  Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. , 2007, Journal of the National Cancer Institute.

[31]  M. Martel,et al.  Postmastectomy radiotherapy of the chest wall: dosimetric comparison of common techniques. , 2002, International journal of radiation oncology, biology, physics.

[32]  I. Lax,et al.  Evaluation of irradiated heart volumes in stage I breast cancer patients treated with postoperative adjuvant radiotherapy. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  F. Davis,et al.  Cancer mortality in a radiation-exposed cohort of Massachusetts tuberculosis patients. , 1989, Cancer research.

[34]  G. Ribeiro,et al.  Mortality patterns over 34 years of breast cancer patients in a clinical trial of post-operative radiotherapy. , 1989, Clinical radiology.

[35]  Mike Clarke,et al.  Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials , 2000 .

[36]  S. Underwood,et al.  Detection of defects in myocardial perfusion imaging in patients with early breast cancer treated with radiotherapy. , 2002, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[37]  D A Pierce,et al.  Studies of the mortality of atomic bomb survivors. Report 12, Part I. Cancer: 1950-1990. , 1996, Radiation research.

[38]  W. Woodward,et al.  Cardiovascular death and second non-breast cancer malignancy after postmastectomy radiation and doxorubicin-based chemotherapy. , 2003, International journal of radiation oncology, biology, physics.

[39]  C. Shapiro,et al.  Side effects of adjuvant treatment of breast cancer. , 2001, The New England journal of medicine.

[40]  T. Wheldon,et al.  Variation in the probability of cardiac complications with radiation technique in early breast cancer. , 2001, The British journal of radiology.

[41]  B. Trock,et al.  Irradiation-related ischemic heart disease. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  L. Noyez,et al.  Use of internal mammary artery in myocardial revascularization after mediastinal irradiation. , 1992, The Journal of thoracic and cardiovascular surgery.

[43]  Nancy P. Mendenhall,et al.  Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy. , 2003 .

[44]  F. Orzan,et al.  Severe coronary artery disease after radiation therapy of the chest and mediastinum: clinical presentation and treatment. , 1993, British heart journal.

[45]  Detection of radiation cardiomyopathy by gated radionuclide angiography. , 1983, The American journal of medicine.

[46]  K. Tolba,et al.  Cardiotoxicity of cancer therapy. , 1999, Cancer investigation.

[47]  D. Cowen,et al.  Thallium-201 perfusion scintigraphy in the evaluation of late myocardial damage in left-side breast cancer treated with adjuvant radiotherapy. , 1998, International journal of radiation oncology, biology, physics.

[48]  B. E. F. Isher,et al.  Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. , 2002 .

[49]  B. Fowble,et al.  Lung and heart dose volume analyses with CT simulator in radiation treatment of breast cancer. , 1998, International journal of radiation oncology, biology, physics.

[50]  H. Bartelink,et al.  Simplified intensity-modulated radiotherapy using pre-defined segments to reduce cardiac complications in left-sided breast cancer. , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[51]  Michael B Sharpe,et al.  Initial clinical experience with moderate deep-inspiration breath hold using an active breathing control device in the treatment of patients with left-sided breast cancer using external beam radiation therapy. , 2003, International journal of radiation oncology, biology, physics.

[52]  R. Hassen-Khodja,et al.  Radiotherapy-induced supra-aortic trunk disease: early and long-term results of surgical and endovascular reconstruction. , 2004, Journal of vascular surgery.

[53]  O. Pahlm,et al.  No serious late cardiac effects after adjuvant radiotherapy following mastectomy in premenopausal women with early breast cancer. , 1999, International journal of radiation oncology, biology, physics.

[54]  Lawrence B Marks,et al.  The incidence and functional consequences of RT-associated cardiac perfusion defects. , 2005, International journal of radiation oncology, biology, physics.

[55]  D. Hollis,et al.  Symptomatic cardiac events following radiation therapy for left-sided breast cancer: possible association with radiation therapy-induced changes in regional perfusion. , 2003, Clinical breast cancer.

[56]  S. Shott,et al.  Three-dimensional photon dosimetry: a comparison of treatment of the intact breast in the supine and prone position. , 2003, International journal of radiation oncology, biology, physics.

[57]  H. Tinteren,et al.  Iodine-123 metaiodobenzylguanidine in the assessment of late cardiac effects from cancer therapy , 1996, European Journal of Nuclear Medicine.

[58]  W. Mackillop,et al.  Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[59]  S. Darby,et al.  Cardiac risks of breast-cancer radiotherapy: a contemporary view. , 2006, Clinical oncology (Royal College of Radiologists (Great Britain)).

[60]  Steven E Lipshultz,et al.  Radiation-associated cardiovascular disease. , 2003, Critical reviews in oncology/hematology.

[61]  I. Lax,et al.  Prediction of excess risk of long-term cardiac mortality after radiotherapy of stage I breast cancer. , 1998, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[62]  C. Land,et al.  Coronary heart disease after radiotherapy for peptic ulcer disease. , 2005, International journal of radiation oncology, biology, physics.

[63]  A. R. Marchese,et al.  Changes in the proportion of types I and III collagen in the left ventricular wall of patients with post-irradiative pericarditis. , 1996, Cardiovascular surgery.

[64]  J. Haybittle,et al.  Postoperative radiotherapy and late mortality: evidence from the Cancer Research Campaign trial for early breast cancer. , 1989, BMJ.

[65]  H. Bartelink,et al.  Determining optimal two-beam axial orientations for heart sparing in left-sided breast cancer patients. , 2003, Medical physics.

[66]  E. Nakashima,et al.  Persistent subclinical inflammation among A-bomb survivors , 2001, International journal of radiation biology.

[67]  B. Rasmussen,et al.  Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial , 1999, The Lancet.

[68]  L. Rutqvist,et al.  Myocardial damage in breast cancer patients treated with adjuvant radiotherapy: a prospective study. , 1996, International journal of radiation oncology, biology, physics.

[69]  R. Peto,et al.  Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. , 2005, The Lancet. Oncology.

[70]  E. Touboul,et al.  Multidisciplinary treatment approach to locally advanced non-inflammatory breast cancer using chemotherapy and radiotherapy with or without surgery. , 1992, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[71]  N. Christakis,et al.  Favorable cardiac risk among elderly breast carcinoma survivors , 2003, Cancer.

[72]  C. Mullany,et al.  Coronary artery bypass grafting in patients with previous mediastinal radiation therapy. , 1999, The Journal of thoracic and cardiovascular surgery.

[73]  D. Glancy,et al.  Management of patients with radiation-induced pericarditis with effusion: a note on the development of aortic regurgitation in two of them. , 1973, Chest.

[74]  W. C. Sheldon,et al.  Clinical and angiographic features of coronary artery disease after chest irradiation. , 1987, The American journal of cardiology.

[75]  W. Casarella,et al.  Subclavian artery occlusion following radiotherapy for carcinoma of the breast. , 1976, Radiology.

[76]  A. Gholkar,et al.  Subclavian artery stenosis presenting as posterior cerebrovascular events after adjuvant radiotherapy for breast cancer. , 1997, Clinical oncology (Royal College of Radiologists (Great Britain)).

[77]  L. Rutqvist,et al.  Long-term cardiac morbidity and mortality in a randomized trial of pre- and postoperative radiation therapy versus surgery alone in primary breast cancer. , 1998, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[78]  R. Doll,et al.  Long term mortality after a single treatment course with X-rays in patients treated for ankylosing spondylitis. , 1987, British Journal of Cancer.

[79]  H. Rodemann,et al.  Cellular basis of radiation-induced fibrosis. , 1995, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[80]  S Webb,et al.  Cardiac avoidance in breast radiotherapy: a comparison of simple shielding techniques with intensity-modulated radiotherapy. , 2001, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[81]  T. Whelan,et al.  Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[82]  D. Birnbaum,et al.  Heart diseases following mediastinal irradiation: surgical management. , 1995, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[83]  L. Strender,et al.  Incidence of heart disease and functional significance of changes in the electrocardiogram 10 years after radiotherapy for breast cancer , 1986, Cancer.

[84]  K. Trott,et al.  Radiation-induced cardiovascular diseases: is the epidemiologic evidence compatible with the radiobiologic data? , 2007, International journal of radiation oncology, biology, physics.

[85]  H. Høst,et al.  Postoperative radiotherapy in breast cancer--long-term results from the Oslo study. , 1986, International journal of radiation oncology, biology, physics.

[86]  L. Rutqvist,et al.  Myocardial infarction among women with early-stage breast cancer treated with conservative surgery and breast irradiation. , 1998, International journal of radiation oncology, biology, physics.

[87]  D. Hollis,et al.  Persistence of radiation (RT)-induced cardiac perfusion defects 3-5 years post RT. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[88]  D A Pierce,et al.  Studies of the mortality of atomic bomb survivors. Report 12, part II. Noncancer mortality: 1950-1990. , 1999, Radiation research.

[89]  J. Silber,et al.  Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. , 1992, The American journal of cardiology.

[90]  Lambert Zijp,et al.  Reduction of cardiac and lung complication probabilities after breast irradiation using conformal radiotherapy with or without intensity modulation. , 2002, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[91]  A. Recht Which breast cancer patients should really worry about radiation-induced heart disease--and how much? , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[92]  J. De Sutter,et al.  The role of nuclear medicine in the prediction and detection of radiation-associated normal pulmonary and cardiac damage. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[93]  John Wong,et al.  MRI-based volumetric assessment of cardiac anatomy and dose reduction via active breathing control during irradiation for left-sided breast cancer. , 2005, International journal of radiation oncology, biology, physics.

[94]  W. Edwards,et al.  Pathology of radiation-induced heart disease: a surgical and autopsy study of 27 cases. , 1996, Human pathology.

[95]  J. Vilcoq,et al.  Breast radiotherapy in the lateral decubitus position: A technique to prevent lung and heart irradiation. , 2005, International journal of radiation oncology, biology, physics.

[96]  K. Zedeler,et al.  Postoperative Radiotherapy in High-Risk Premenopausal Women with Breast Cancer Who Receive Adjuvant Chemotherapy , 1997 .

[97]  Lena Specht,et al.  Breathing adapted radiotherapy for breast cancer: comparison of free breathing gating with the breath-hold technique. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[98]  C. Shapiro,et al.  Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[99]  G. Bonadonna,et al.  Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[100]  B Fisher,et al.  Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. , 1985, The New England journal of medicine.

[101]  K. Kodama,et al.  Radiation dose-dependent increases in inflammatory response markers in A-bomb survivors , 2003, International journal of radiation biology.

[102]  J. Goodwin,et al.  Cardiac morbidity of adjuvant radiotherapy for breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[103]  Stine Korreman,et al.  Breathing adapted radiotherapy of breast cancer: reduction of cardiac and pulmonary doses using voluntary inspiration breath-hold. , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[104]  G. Amromin,et al.  THE SYNERGISM OF X-IRRADIATION AND CHOLESTEROL-FAT FEEDING ON THE DEVELOPMENT OF CORONARY ARTERY LESIONS. , 1964, Journal of atherosclerosis research.

[105]  L. Rutqvist,et al.  Morbidity of ischemic heart disease in early breast cancer 15-20 years after adjuvant radiotherapy. , 1994, International journal of radiation oncology, biology, physics.

[106]  M. Schipper,et al.  Cardiac chamber and coronary artery doses associated with postmastectomy radiotherapy techniques to the chest wall and regional nodes. , 2004, International journal of radiation oncology, biology, physics.

[107]  S. Hancock,et al.  Diastolic dysfunction after mediastinal irradiation. , 2005, American heart journal.

[108]  G. Gyenes Radiation-induced ischemic heart disease in breast cancer--a review. , 1998, Acta oncologica.

[109]  Anthony Howell,et al.  Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials. , 1995, The New England journal of medicine.

[110]  R. Doll,et al.  Mortality in a cohort of women given X‐ray therapy for metropathia haemorrhagica , 1994, International journal of cancer.

[111]  C. Rose,et al.  A Systematic Overview of Radiation Therapy Effects in Breast Cancer , 2003, Acta oncologica.

[112]  J. Alexander,et al.  Radiation-associated valvular disease. , 1991, Chest.

[113]  John J Spinelli,et al.  Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. , 2005, Journal of the National Cancer Institute.

[114]  Sarah C. Darby,et al.  Low Doses of Ionizing Radiation and Circulatory Diseases: A Systematic Review of the Published Epidemiological Evidence , 2005, Radiation research.

[115]  O. Migneco,et al.  Acute cardiac effects of mediastinal irradiation: assessment by radionuclide angiography. , 1992, International journal of radiation oncology, biology, physics.

[116]  Michael B Sharpe,et al.  Significant reductions in heart and lung doses using deep inspiration breath hold with active breathing control and intensity-modulated radiation therapy for patients treated with locoregional breast irradiation. , 2003, International journal of radiation oncology, biology, physics.

[117]  Robert W. Harris,et al.  Management of arterial occlusive radiation therapy , 1996 .

[118]  M Baum,et al.  Overview of randomized trials of postoperative adjuvant radiotherapy in breast cancer. , 1988, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[119]  J. De Sutter,et al.  The clinical value of nuclear medicine in the assessment of irradiation-induced and anthracycline-associated cardiac damage. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[120]  D P Dearnaley,et al.  Cardiovascular disease as a long-term complication of treatment for testicular cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[121]  S L Hancock,et al.  Factors affecting late mortality from heart disease after treatment of Hodgkin's disease. , 1993, JAMA.

[122]  J. R. Stewart,et al.  Radiation injury to the heart. , 1995, International journal of radiation oncology, biology, physics.

[123]  I. Lax,et al.  Partial irradiation of the heart. , 2001, Seminars in radiation oncology.

[124]  G. Gyenes,et al.  Pericardial irritation in breast cancer patients treated by curative postoperative radiotherapy--early results. , 1991, Strahlentherapie und Onkologie (Print).

[125]  V. Devita,et al.  Cancer : Principles and Practice of Oncology , 1982 .

[126]  W. Wei,et al.  Carotid stenosis after radiotherapy for nasopharyngeal carcinoma. , 2000, Archives of otolaryngology--head & neck surgery.

[127]  P. Kaufmann,et al.  Cardiac risk after mediastinal irradiation for Hodgkin's disease. , 1998, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[128]  P. Canney,et al.  Developments in radiotherapy. , 1997, Cancer treatment reviews.

[129]  J. Wondergem,et al.  Circulating atrial natriuretic peptide plasma levels as a marker for cardiac damage after radiotherapy. , 2001, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[130]  R. Stroobandt,et al.  Radiation-induced heart disease. , 1975, Acta cardiologica.

[131]  P. Munk,et al.  Carotid artery stenosis in patients who have undergone radiation therapy for head and neck malignancy. , 1998, The British journal of radiology.

[132]  J. Overgaard,et al.  Late Treatment-Related Morbidity in Breast Cancer Patients Randomized to Postmastectomy Radiotherapy and Systemic Treatment Versus Systemic Treatment Alone , 2000 .

[133]  D. R. Harper,et al.  Thrombosis of the subclavian‐axillary artery following radiotherapy for carcinoma of the breast , 1973, The British journal of surgery.

[134]  M. Böhm,et al.  Radiation-induced heart disease: morphology, changes in catecholamine synthesis and content, beta-adrenoceptor density, and hemodynamic function in an experimental model. , 1992, Radiation research.

[135]  D. Rades,et al.  Long-term radiation sequelae after breast-conserving therapy in women with early-stage breast cancer: an observational study using the LENT-SOMA scoring system. , 2003, International journal of radiation oncology, biology, physics.

[136]  E. Perez,et al.  Adjuvant radiotherapy (RT) and trastuzumab in stage I-IIA breast cancer: Toxicity data from North Central Cancer Treatment Group Phase III trial N9831. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[137]  R. Doll,et al.  100 years of observation on British radiologists: mortality from cancer and other causes 1897-1997. , 2001, The British journal of radiology.

[138]  J. Manola,et al.  No long-term increase in cardiac-related mortality after breast-conserving surgery and radiation therapy using modern techniques. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[139]  R. Ross,et al.  Atherosclerosis is an inflammatory disease. , 1998, American heart journal.

[140]  B. Niederle,et al.  Irradiation-induced changes in the subclavian and axillary arteries after radiotherapy for carcinoma of the breast. , 1986, Surgery.

[141]  M. Hauptmann,et al.  Mortality from diseases of the circulatory system in radiologic technologists in the United States. , 2003, American journal of epidemiology.

[142]  J. Lebesque,et al.  Cardiac and lung complication probabilities after breast cancer irradiation. , 2000, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[143]  C. Blomqvist,et al.  The combination of radiotherapy, adjuvant chemotherapy (cyclophosphamide-doxorubicin-ftorafur) and tamoxifen in stage II breast cancer. Long-term follow-up results of a randomised trial. , 1992, British Journal of Cancer.

[144]  J. Klijn,et al.  Decreased risk of stroke among 10-year survivors of breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[145]  L. Constine,et al.  Radiation-associated cardiovascular disease: manifestations and management. , 2003, Seminars in radiation oncology.

[146]  M Baum,et al.  Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[147]  J. Klijn,et al.  Cause-specific mortality in long-term survivors of breast cancer: A 25-year follow-up study. , 2006, International journal of radiation oncology, biology, physics.

[148]  W. Manning,et al.  Reduction of cardiac volume in left-breast treatment fields by respiratory maneuvers: a CT study. , 2000, International journal of radiation oncology, biology, physics.

[149]  Wei-Ting Hwang,et al.  Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[150]  L. Marks,et al.  Radiation-induced heart disease: vigilance is still required. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[151]  P. C. Williams,et al.  Use of electronic portal imaging to assess cardiac irradiation in breast radiotherapy. , 1997, Clinical oncology (Royal College of Radiologists (Great Britain)).

[152]  A. Kuten,et al.  Subclavian artery occlusion after radiotherapy for carcinoma of the breast , 1988, Cancer.

[153]  L. Marks,et al.  Cardiac perfusion changes in patients treated for breast cancer with radiation therapy and doxorubicin: preliminary results. , 2001, International journal of radiation oncology, biology, physics.

[154]  L. F. Fajardo,et al.  Morphology of radiation-induced heart disease. , 1968, Archives of pathology.

[155]  L. Marks,et al.  Cardiac toxicity following thoracic radiation. , 2005, Seminars in oncology.

[156]  L. Holmberg,et al.  Increased incidence of stroke in women with breast cancer. , 2005, European journal of cancer.