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      Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer

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          Abstract

          Background:

          Radiation-related heart disease and lung cancer can occur following radiotherapy for breast cancer but the duration of any mortality risk is uncertain.

          Methods:

          Mortality ratios, by laterality of breast cancer, were estimated using Poisson regression for 558 871 women recorded with breast cancer during 1973–2008 in the Surveillance, Epidemiology and End Results (SEER) cancer registries and followed until 01 January 2009.

          Results:

          For women diagnosed with breast cancer during 1973–1982 and given radiotherapy shortly afterwards, the cardiac mortality ratios, left-sided vs right-sided, were 1.19 (1.03–1.38), 1.35 (1.05–1.73), 1.64 (1.26–2.14) and 1.90 (1.52–2.37) at <10, 10–14, 15–19 and 20+ years since diagnosis (2 p for trend: <0.001). The lung cancer mortality ratios, ipsilateral vs contralateral, in these women were 1.05 (0.57–1.94), 2.04 (1.28–3.23) and 3.87 (2.19–6.82) at <10, 10–19 and 20+ years, respectively, (2 p for trend: 0.002). For women irradiated during 1983–92 there was evidence of radiation-related mortality for lung cancer, but not for heart disease. For women irradiated since 1993 there is, as yet, little evidence of any radiation-related mortality.

          Conclusion:

          In this population, the radiation-related risks were larger in the third decade after exposure than during the first two decades.

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          Most cited references7

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          Dosimetric comparison of left-sided whole breast irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical tomotherapy, and topotherapy.

          To compare left-sided whole breast conventional and intensity-modulated radiotherapy (IMRT) treatment planning techniques. Treatment plans were created for 10 consecutive patients. Three-dimensional conformal radiotherapy (3DCRT), forward-planned IMRT (for-IMRT), and inverse-planned IMRT (inv-IMRT) used two tangent beams. For-IMRT utilized up to four segments per beam. For helical tomotherapy (HT) plans, beamlet entrance and/or exit to critical structures was blocked. Topotherapy plans, which used static gantry angles with simultaneous couch translation and inverse-planned intensity modulation, used two tangent beams. Plans were normalized to 50Gy to 95% of the retracted PTV. Target max doses were reduced with for-IMRT compared to 3DCRT, which were further reduced with HT, topotherapy, and inv-IMRT. HT resulted in lowest heart and ipsilateral lung max doses, but had higher mean doses. Inv-IMRT and topotherapy reduced ipsilateral lung mean and max doses compared to 3DCRT and for-IMRT. All modalities evaluated provide adequate coverage of the intact breast. HT, topotherapy, and inv-IMRT can reduce high doses to the target and normal tissues, although HT results in increased low doses to large volume of normal tissue. For-IMRT improves target homogeneity compared with 3DCRT, but to a lesser degree than the inverse-planned modalities. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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            Lung cancer risk and radiation dose among women treated for breast cancer.

            Evidence shows ionizing radiation can cause lung cancer, but few studies have quantified risk in relation to radiation dose. This study evaluated the long-term risk of lung cancer among women treated with radiation for breast cancer. In this case-referent study, the Connecticut Tumor Registry was used to identify women diagnosed with histologically confirmed invasive breast cancer between 1935 and 1971 who survived for at least 10 years (8976) and to ascertain lung cancers occurring in this group between 1945 and 1981. Seventy-six cases of lung cancer were identified; however, 15 cases did not meet the criteria for inclusion. For the 61 remaining lung cancer case patients and 120 reference subjects (selected from the same registry and matched according to race, age at breast cancer diagnosis, year of breast cancer diagnosis, and survival without a second primary tumor), hospital charts were reviewed to collect medical history and radiotherapy information. A medical physicist estimated radiation dose to different segments of the lungs on the basis of radiotherapy reports and experimental simulations of treatments. For these 10-year survivors of breast cancer, the overall relative risk (RR) of lung cancer associated with initial radiotherapy for breast cancer was 1.8 (95% confidence interval [CI] = 0.8-3.8), and the RR increased with time following treatment. The RR for periods of 15 years or more after radiotherapy was 2.8 (95% CI = 1.0-8.2). Mean dose was 15.2 Gy to the ipsilateral lung, 4.6 Gy to the contralateral lung, and 9.8 Gy for both lungs combined. The excess RR was 0.08 per Gy, based on average dose to both lungs, and 0.20 per Gy to the affected (cancerous) lung. Breast cancer radiotherapy regimens in use before the 1970s were associated with an elevated lung cancer risk many years following treatment. The estimated risk coefficients are lower than those reported for atomic bomb survivors. The lower than expected risk might be attributable to high-dose cell killing or the fractionated nature of the exposure. Approximately nine cases of radiotherapy-induced lung cancer per year would be expected to occur among 10,000 women who received an average lung dose of 10 Gy and survived for at least 10 years. Current radiotherapy for breast cancer results in less extensive exposure of the lungs in comparison to treatments of years past, and the risk of secondary lung cancer need not play a major role in clinical decisions regarding treatment for breast cancer. Nonetheless, efforts to reduce unnecessary exposure of the lungs and heart should continue to further reduce possible adverse radiation effects.
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              Ionizing radiation and tobacco use increases the risk of a subsequent lung carcinoma in women with breast cancer: case-only design.

              To analyze the risk of lung cancer in women treated with radiotherapy for breast cancer. We accessed the lung dose in relation to different radiotherapy techniques, provided the excess relative risk (ERR) estimate for radiation-associated lung cancer, and evaluated the influence of tobacco use. The Swedish Cancer Registry was used to identify 182 women diagnosed with breast and subsequent lung cancers in Stockholm County during 1958 to 2000. Radiotherapy was administered to 116 patients. Radiation dose was estimated from the original treatment charts, and information on smoking history was searched for in case records and among relatives. The risk of lung cancer was assessed in a case-only approach, where each woman contributed a pair of lungs. The average mean lung dose to the ipsilateral lung was 17.2 Gy (range, 7.1 to 32.0 Gy). A significantly increased relative risk (RR) of a subsequent ipsilateral lung cancer was observed at > or = 10 years of follow-up (RR = 2.04; 95% CI, 1.24 to 3.36). Squamous cell carcinoma (RR = 4.00; 95% CI, 1.50 to 10.66) was the histopathologic subgroup most closely related to ionizing radiation. The effect of radiotherapy was restricted to smokers only (RR = 3.08; 95% CI, 1.61 to 5.91). The ERR/Gy for women with latency > or = 10 years after exposure was 0.11 (95% CI, 0.02 to 0.44). Radiotherapy for breast cancer significantly increases the risk of lung carcinoma more than 10 years after exposure in women who smoked at time of breast cancer.
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                Author and article information

                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                15 January 2013
                20 December 2012
                15 January 2013
                : 108
                : 1
                : 179-182
                Affiliations
                [1 ]Clinical Trial Service Unit (CTSU), University of Oxford , Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
                Author notes
                Article
                bjc2012575
                10.1038/bjc.2012.575
                3553540
                23257897
                cf5cd7de-f332-418d-9898-24399798829a
                Copyright © 2013 Cancer Research UK

                This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                History
                : 17 August 2012
                : 13 November 2012
                : 20 November 2012
                Categories
                Short Communication

                Oncology & Radiotherapy
                epidemiology,breast cancer radiotherapy,radiation-related heart disease,radiation-related lung cancer,long-term effects,mortality

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