Risk of ischemic heart disease in women after radiotherapy for breast cancer.
ABSTRACT 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.).
- Radioprotection 04/2014; 49(2):135-138. DOI:10.1051/radiopro/2013099 · 0.60 Impact Factor
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ABSTRACT: Blocks have been used to protect heart from potential radiation damage in left-sided breast treatments. Since cardiac motion pattern may not be fully captured on conventional 3DCT or 4DCT simulation scans, this study was intended to investigate the optimization of the heart block design taking the cardiac motion into consideration. Whole breast treatment plans using two opposed tangential fields were designed based on 4DCT simulation images for 10 left-sided breast cancer patients. Using an OBI system equipped to a Varian Linac, beam-eye viewed fluoroscopy images were acquired for each of the treatment beams after patient treatment setup, and the MLC heart blocks were overlaid onto the fluoroscopy images with an in-house software package. A non-rigid image registration and tracking algorithm was utilized to track the cardiac motion on the fluoroscopy images with minimal manual delineation for initialization, and the tracked cardiac motion information was used to optimize the heart block design to minimize the radiation damage to heart while avoiding the over-shielding that may lead to underdosing certain breast tissues. Twenty-three sets of fluoroscopy images were acquired on 23 different days of treatment for the 10 patients. As expected, heart moved under the influences of both respiratory and cardiac motion. It was observed that for 16 out of the 23 treatments, heart moved beyond the planed heart block into treatment fields and MLC had to be adjusted to fully block heart. The adjustment was made for all but one patient. The number of the adjusted MLC leaves ranged from 1 to 16 (mean = 10), and the MLC leaf position adjustment ranged from 2 to 10 mm (mean = 6 mm). The added heart block areas ranged from 3 to 1230 mm(2) (mean = 331 mm(2)). In left-sided whole breast radiation treatments, simulation CT (and 4DCT) based heart block design may not provide adequate heart protection for all the treatments. A fluoroscopy-based method has been developed to adaptively optimize the heart MLC block to achieve optimal heart protection.Frontiers in Oncology 12/2014; 4:342. DOI:10.3389/fonc.2014.00342
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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; DOI:10.1016/j.ijheh.2015.01.007 · 3.28 Impact Factor