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Background: Radiation therapy (RT) to the left breast/chest wall has been linked with cardiac dysfunction. Previously, the authors identified cardiac perfusion defects in approximately 50% to 60% of patients 0.5 to 2 years post-RT. In the current study, they assessed the persistence of these defects 3 to 6 years post-RT. Methods: From 1998 to 2006, 160 patients with left-sided breast cancer were enrolled onto an Institutional Review Board-approved, prospective study. All patients received tangential photons to the left breast/chest wall. Patients had pre-RT and serial post-RT single-photon emission computed tomography (SPECT) scans to assess changes in regional cardiac perfusion, wall motion, and ejection fraction (EF). Forty-four patients had SPECT scans 3 to 6 years post-RT and were evaluable for the current analysis. Results: The overall incidence of perfusion defects at 3 years, 4 years, 5 years, and 6 years was 52% (11 of 21 patients), 71% (17 of 24 patients), 67% (12 of 18 patients), and 57% (4 of 7 patients), respectively. The rate of abnormal SPECT scans 3 to 6 years post-RT in patients who had scans at 0.5 to 2 years that were either all abnormal, intermittently abnormal, or all normal was 80%, 67%, and 63%, respectively. The incidence of wall motion abnormalities in patients with or without perfusion defects 3 to 6 years post-RT was low and did not differ statistically (17% vs 7.1%, respectively; P = .65), as was the incidence of reductions in EF of >/=5% (27% vs 36%, respectively; P = .72). Conclusions: The results from this study indicated that RT-induced perfusion defects may persist or initially may appear 3 to 6 years post-RT in a high percentage of patients. However, these defects were not associated with changes in regional wall motion or EF. Additional study will be needed to determine the clinical relevance of these defects. In the meantime, the authors believe that every effort should be made to minimize incidental irradiation of the heart while maintaining adequate coverage of target volumes. [ABSTRACT FROM AUTHOR]