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Title: Reassessing the Time Course for Radiation-Induced Cardiac Mortality in Patients With Breast Cancer


No abstract prepared.

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Publication Date:
OSTI Identifier:
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 97; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States

Citation Formats

Marks, Lawrence B., E-mail:, Zagar, Timothy M., and Kaidar-Person, Orit. Reassessing the Time Course for Radiation-Induced Cardiac Mortality in Patients With Breast Cancer. United States: N. p., 2017. Web. doi:10.1016/J.IJROBP.2016.10.036.
Marks, Lawrence B., E-mail:, Zagar, Timothy M., & Kaidar-Person, Orit. Reassessing the Time Course for Radiation-Induced Cardiac Mortality in Patients With Breast Cancer. United States. doi:10.1016/J.IJROBP.2016.10.036.
Marks, Lawrence B., E-mail:, Zagar, Timothy M., and Kaidar-Person, Orit. Wed . "Reassessing the Time Course for Radiation-Induced Cardiac Mortality in Patients With Breast Cancer". United States. doi:10.1016/J.IJROBP.2016.10.036.
title = {Reassessing the Time Course for Radiation-Induced Cardiac Mortality in Patients With Breast Cancer},
author = {Marks, Lawrence B., E-mail: and Zagar, Timothy M. and Kaidar-Person, Orit},
abstractNote = {No abstract prepared.},
doi = {10.1016/J.IJROBP.2016.10.036},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 97,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2017},
month = {Wed Feb 01 00:00:00 EST 2017}
  • Purpose: The benefits of adjuvant radiation therapy (RT) for breast cancer may be counterbalanced by the risk of cardiac toxicity. We studied the cardiac effects of RT and the impact of pre-existing cardiac risk factors (CRFs) in a population-based sample of older patients with breast cancer. Methods and Materials: In the Surveillance, Epidemiology and End-Results (SEER)-Medicare database of women {>=}65 years diagnosed with Stages I to III breast cancer from January 1, 1992 to December 31, 2000, we used multivariable logistic regression to model the associations of demographic and clinical variables with postmastectomy and postlumpectomy RT. Using Cox proportional hazardsmore » regression, we then modeled the association between treatment and myocardial infarction (MI) and ischemia in the 10 or more years after diagnosis, taking the predictors of treatment into account. Results: Among 48,353 women with breast cancer; 19,897 (42%) were treated with lumpectomy and 26,534 (55%) with mastectomy; the remainder had unknown surgery type (3%). Receipt of RT was associated with later year of diagnosis, younger age, fewer comorbidities, nonrural residence, and chemotherapy. Postlumpectomy RT was also associated with white ethnicity and no prior history of heart disease (HD). The RT did not increase the risk of MI. Presence of MI was associated with age, African American ethnicity, advanced stage, nonrural residence, more than one comorbid condition, a hormone receptor-negative tumor, CRFs and HD. Among patients who received RT, tumor laterality was not associated with MI outcome. The effect of RT on the heart was not influenced by HD or CRFs. Conclusion: It appears unlikely that RT would increase the risk of MI in elderly women with breast cancer, regardless of type of surgery, tumor laterality, or history of CRFs or HD, for at least 10 years.« less
  • Purpose: To explore very-long-term mortality from ischemic heart disease (IHD) after locoregional radiation therapy of breast cancer (BC) in relation to degree of hypofractionation and other treatment variables. Methods and Materials: Two hypofractionated regimens used for locoregional radiation therapy for BC from 1975 to 1991 were considered. Patients received 4.3 Gy × 2/week (10 fractions; target dose 43 Gy; n=1107) or 2.5 Gy × 5/week (20 fractions; target dose 50 Gy; n=459). To estimate cardiac doses, radiation fields were reconstructed in a planning system. Time to death from IHD was the endpoint, comparing the groups with each other and withmore » age-matched, cancer-free control individuals, modeled with the Cox proportional hazards model. Results: Patients given 4.3 Gy × 10 had an increased risk of dying of IHD compared with both the 2.5 Gy group (hazard ratio [HR] = 2.37; 95% confidence interval [CI]: 1.06-5.32; P=.036) and the control group (HR = 1.59; 95% CI: 1.13-2.23; P=.008). Photon beams for parasternal fields gave an increased risk of dying of IHD compared with electron beams (HR = 2.56; 95% CI: 1.12-5.84; P=.025). Multivariate analysis gave an increased risk for the 4.3-Gy versus 2.5-Gy regimen with borderline significance (HR = 2.90; 95% CI: 0.97-8.79; P=.057) but not for parasternal irradiation. Conclusions: The degree of hypofractionation and parasternal photon beams contributed to increased cardiac mortality in this patient cohort. Differences emerged after 12 to 15 years, indicating the need of more studies with observation time of 2 decades.« less
  • Objectives: Radiation therapy for left-sided breast cancer has been associated with an elevated risk of cardiac mortality, based on studies predating treatment planning based on computed tomography. This study assessed the impact of tumor laterality on overall survival (OS) in a large cohort treated with modern techniques, to indirectly determine whether left-sided treatment remains associated with increased cardiac mortality. Methods and Materials: Patients treated for breast cancer with breast conserving surgery and adjuvant external beam radiation therapy were identified in the National Cancer Database, and OS was compared based on tumor laterality using Kaplan-Meier analysis. Separate analyses were performed formore » noninvasive and invasive carcinoma and for breast-only and breast plus regional nodal radiation therapy. Multivariate regression analysis of OS was performed with demographic, pathologic, and treatment variables as covariates to adjust for factors associated with breast cancer–specific survival. Results: We identified 344,831 patients whose cancer was diagnosed from 1998 to 2006 with a median follow-up time of 6.04 years (range, 0-14.17 years). Clinical, tumor, and treatment characteristics were similar between laterality groups. Regional nodal radiation was used in 14.2% of invasive cancers. No OS difference was noted based on tumor laterality for patients treated with breast-only (hazard ratio [HR] 0.984, P=.132) and breast plus regional nodal radiation therapy (HR 1.001, P=.957). In multivariate analysis including potential confounders, OS was identical between left and right sided cancers (HR 1.002, P=.874). No significant OS difference by laterality was observed when analyses were restricted to patients with at least 10 years of follow-up (n=27,725), both in patients treated with breast-only (HR 0.955, P=.368) and breast plus regional nodal radiation therapy (HR 0.859, P=.155). Conclusions: Radiation therapy for left-sided breast cancer does not appear to increase the risk of death in this national database relative to right-sided tumors. Consequently, radiation therapy–induced cardiac disease may be less prominent than previously demonstrated.« less
  • Purpose: To investigate the occurrence of early radiation-induced changes in regional cardiac function using strain rate imaging (SRI) by tissue Doppler echocardiography. Methods and Materials: We included 20 left-sided and 10 right-sided breast cancer patients receiving radiotherapy (RT) to the breast or chest wall. Standard echocardiography and SRI were performed before RT (baseline), immediately after RT (post-RT), and at 2 months follow-up (FUP) after RT. Regional strain (S) and strain rate (SR) values were obtained from all 18 left ventricular (LV) segments. Data were compared to the regional radiation dose. Results: A reduction in S was observed post-RT and atmore » FUP in left-sided patients (S{sub post-RT}: -17.6 {+-} 1.5%, and S{sub FUP}: -17.4 {+-} 2.3%, vs. S{sub baseline}: -19.5 {+-} 2.1%, p < 0.001) but not in right-sided patients. Within the left-sided patient group, S and SR were significantly reduced after RT in apical LV segments (S{sub post-RT}: -15.3 {+-} 2.5%, and S{sub FUP}: -14.3 {+-} 3.7%, vs. S{sub baseline}: -19.3 {+-} 3.0%, p < 0.01; and SR{sub post-RT}: -1.06 {+-} 0.15 s {sup -1}, and SR{sub FUP}: -1.16 {+-} 0.28 s {sup -1}, vs. SR{sub baseline}: -1.29 {+-} 0.27s {sup -1}, p = 0.01), but not in mid- or basal segments. Furthermore, we observed that segments exposed to more than 3 Gy showed a significant decrease in S after RT (S{sub post-RT}: -16.1 {+-} 1.6%, and S{sub FUP}: -15.8 {+-} 3.4%, vs. S{sub baseline}: -18.9 {+-} 2.6%, p < 0.001). This could not be observed in segments receiving less than 3 Gy. Conclusions: SRI shows a dose-related regional decrease in myocardial function after RT. It might be a useful tool in the evaluation of modern RT techniques, with respect to cardiac toxicity.« less
  • The relationship between exposure to low-linear energy transfer ionizing radiation and subsequent breast cancer mortality risk is reported based on a further 7 years of follow-up in the Canadian fluoroscopy study. Amongst 31,917 women first treated for tuberculosis in a Canadian institution between 1930 and 1952, a total of 688 breast cancer deaths were observed between 1950 and 1987. There is a strong linear trend of increasing risk with increasing dose (P < 0.0001), with the excess relative risk per sievert decreasing with age at exposure (P = 0.0003). The excess relative risk is approximately constant between 5 and 39more » years after exposure, with a suggestion of a decrease between 40 and 57 years after exposure, though this could be a chance effect (P = 0.22). Combined analyses of the Canadian fluoroscopy data and the data for the atomic bomb survivors with respect to breast cancer mortality are also reported. In general the two studies are reasonably consistent, the only distinct difference being the much greater excess relative risk per sievert amongst women exposed to very high doses in the province of Nova Scotia (P, heterogeneity <0.0001). Based on the combined data sets of simple relative risk (RR) model for the effect of a dose of D sieverts at age A years is developed: RR(D) = 1.0 + 0.52D exp[-0.10(A - 15)]. This model fits the combined data well, and is used to predict excess lifetime risks of breast cancer mortality after radiation exposure from routine annual mammography. 20 refs., 12 tabs.« less