Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer

Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom.
New England Journal of Medicine (Impact Factor: 55.87). 03/2013; 368(11):987-98. DOI: 10.1056/NEJMoa1209825
Source: PubMed


Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain.
We conducted a population-based case-control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart.
The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy.
Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.).

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    • "Adjuvant radiotherapy for breast cancer is a beneficial treatment to reduce breast cancer mortality in many categories of women. However , a significant increase in deaths from cardiovascular disease has been specifically reported in women with left-sided breast cancer (EBCTCG, 2005; Darby et al., 2013). An increased risk of cardiovascular disease has also been demonstrated in survivors of childhood cancers (leukemia, brain cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, kidney cancer, neuroblastoma, soft tissue sarcoma, or bone cancer) diagnosed under the age of 21 years between 1970 and 1986. "
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    ABSTRACT: Atherosclerosis is associated with DNA damage in both circulating and vessel-wall cells and DNA adducts derived from exposure to environmental mutagens are abundant in atherosclerotic vessels. Environmental chemical carcinogens identified as risk factor for atherosclerosis include polycyclic aromatic hydrocarbons (benzo(a)pyrene, dimethylbenz(a)anthracene, beta-naphthoflavone, pyrene, 3-methylcolanthrene), arsenic, cadmium, 1,3-butadiene, cigarette smoke. Accordingly, polymorphisms of genes encoding for phase I/II metabolic reaction and DNA repair are risk factor for cardiovascular diseases, although their role is negligible as compared to other risk factors. The pathogenic relevance of mutation-related molecular damage in atherosclerosis has been demonstrated in experimental animal models involving the exposure to chemical mutagens. The relevance of mutation-related events in worsening atherosclerosis prognosis has been demonstrated in human clinical studies mainly as referred to mitochondrial DNA damage. Atherosclerosis is characterized by the occurrence of high level of oxidative damage in blood vessel resulting from both endogenous and exogenous sources. Mitochondrial damage is a main endogenous source of oxidative stress whose accumulation causes activation of intrinsic apoptosis through BIRC2 inhibition and cell loss contributing to plaque development and instability. Environmental physical mutagens, including ionizing radiation, are a risk factor for atherosclerosis even at the low exposure dose occurring in case of occupational exposure or the high exposure doses occurring during radiotherapy. Conversely, the role of exciting UV radiation in atherosclerosis is still uncertain. This review summarizes the experimental and clinical evidence supporting the pathogenic role of mutation-related pathway in atherosclerosis examining the underlying molecular mechanisms. Copyright © 2015 Elsevier GmbH. All rights reserved.
    International Journal of Hygiene and Environmental Health 02/2015; 218(3). DOI:10.1016/j.ijheh.2015.01.007 · 3.83 Impact Factor
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    • "Brachytherapy is widely applied in breast cancer treatment. One of its types – accelerated partial breast irradiation – is time-saving and it has cosmetic advantages and enables preservation of normal organs such as heart and lungs [13]. The use of accelerated partial breast irradiation brachytherapy is consistently increasing. "
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    ABSTRACT: Background and objective The internal mammary lymph nodes (IMN) have been recognized as a potential site of regional breast cancer spread. The aim of this study was to evaluate the impact of internal mammary node radiotherapy (RT) to on clinical outcomes in breast cancer patients treated with mastectomy and postoperative radiation therapy. Materials and methods This cohort study included 588 patients with breast cancers located in the central and medial quadrants. IMN RT was applied to 320 patients and 268 patients did not receive it IMN RT. Inside the IMN RT group, 165 patients received external beam IMN irradiation (IMN-EB). Mastectomy combined with using Californium-252 neutron source implantation was applied to 155 patients (IMN-BT). Cox proportional hazards modeling was used to determine the influence of IMN RT on clinical outcome. Age, tumor size, lymph nodal status, adjuvant radiotherapy, chemotherapy and hormonal therapy were assessed. Results IMN-EB resulted in a significant improvement of distant metastasis-free survival, breast cancer-specific survival and overall survival (P = 0.033, P = 0.037 and P = 0.011, respectively). The IMN-EB radiotherapy has a significant impact on event-free survival (HR, 0.67; 95% CI, 0.46–0.91; P = 0.043) and breast cancer-specific survival (HR, 0.64; 95% CI, 45–0.91; P = 0.013) in patients with moderate-risk (stage T1–2 N1). There was no association between IMN RT and clinical outcomes of patients with high-risk disease (stage T3–4 N2–3) in any of the study end points. Conclusions The effects of IMN-EB radiotherapy on event-free survival and breast cancer-specific survival were benefit for women with moderate-risk breast cancer.
    Medicina (Kaunas, Lithuania) 12/2014; 50(4). DOI:10.1016/j.medici.2014.09.010 · 0.49 Impact Factor
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    • "Because the effect of RT on the subsequent risk of ischemic heart disease is uncertain, a population-based case–control study was conducted of major coronary events in breast cancer patients who underwent RT between 1958 and 2001 [29]. The results were presented by Sarah Darby (Oxford University, UK). "
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    ABSTRACT: MELODI is the European platform dedicated to low-dose radiation risk research. From 7 October through 10 October 2013 the Fifth MELODI Workshop took place in Brussels, Belgium. The workshop offered the opportunity to 221 unique participants originating from 22 countries worldwide to update their knowledge and discuss radiation research issues through 118 oral and 44 poster presentations. In addition, the MELODI 2013 workshop was reaching out to the broader radiation protection community, rather than only the low-dose community, with contributions from the fields of radioecology, emergency and recovery preparedness, and dosimetry. In this review, we summarise the major scientific conclusions of the workshop, which are important to keep the MELODI strategic research agenda up-to-date and which will serve to establish a joint radiation protection research roadmap for the future.
    Journal of Radiological Protection 11/2014; 34(4):931-956. DOI:10.1088/0952-4746/34/4/931 · 1.70 Impact Factor
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