CLINICAL INVESTIGATION Breast FAT NECROSIS AFTER PARTIAL-BREAST IRRADIATION WITH BRACHYTHERAPY OR ELECTRON IRRADIATION VERSUS STANDARD WHOLE-BREAST RADIOTHERAPY— 4-YEAR RESULTS OF A RANDOMIZED TRIAL KATALIN LO ¨ VEY, M.D.,* JA ´ NOS FODOR, M.D., PH.D., D.SC.,* TIBOR MAJOR, M.SC., PH.D.,* E ´ VA SZABO ´ , M.D., y ZSOLT OROSZ, M.D., PH.D., z ZOLTA ´ N SULYOK, M.D., x LEVENTE JA ´ NVA ´ RY, M.D.,* GEORGINA FRO ¨ HLICH,* MIKLO ´ S KA ´ SLER, M.D., PH.D.,* AND CSABA POLGA ´ R, M.D., PH.D.* Departments of *Radiotherapy, y Diagnostic Radiology, z Human and Experimental Tumor Pathology, and x General and Thoracic Surgery, National Institute of Oncology, Budapest, Hungary Purpose: To examine the incidence and clinical relevance of fat necrosis after accelerated partial-breast irradiation (PBI) using interstitial high-dose-rate brachytherapy (HDR-BT) in comparison with partial-breast electron irradiation (ELE) and whole-breast irradiation (WBI). Methods and Materials: Between 1998 and 2004, 258 early-stage breast cancer patients were randomized to re- ceive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 Â 5.2 Gy HDR-BT (n = 88) or 50 Gy ELE (n = 40). The incidence of fat necrosis, its impact on cosmetic outcome, accompanying radiologic features, and clinical symptoms were evaluated. Results: The 4-year actuarial rate of fat necrosis was 31.1% for all patients, and 31.9%, 36.5%, and 17.7% after WBI, HDR-BT and ELE, respectively (p WBI/HDR-BT = 0.26; p WBI/ELE = 0.11; p ELE/HDR-BT = 0.025). The respective rate of asymptomatic fat necrosis was 20.2%, 25.3%, and 10% of patients. The incidence of symptomatic fat necrosis was not significantly different after WBI (8.5%), HDR-BT (11.4%), and ELE (7.5%). Symptomatic fat necrosis was significantly associated with a worse cosmetic outcome, whereas asymptomatic fat necrosis was not. Fat necrosis was detectable with mammography and/or ultrasound in each case. Additional imaging examinations were required in 21% of cases and aspiration cytology in 42%. Conclusions: Asymptomatic fat necrosis is a common adverse event of breast-conserving therapy, having no significant clinical relevance in the majority of the cases. The incidence of both symptomatic and asymptomatic fat necrosis is similar after conventional WBI and accelerated partial-breast HDR-BT. Ó 2007 Elsevier Inc. Fat necrosis, Side effects, High-dose-rate brachytherapy, Accelerated partial-breast irradiation, Breast-conserv- ing therapy. INTRODUCTION Fat necrosis of the breast is a benign inflammatory process that mostly occurs after any trauma of the breast; however the exact etiology of this condition is still unclear (1, 2). Retrospective studies suggest that, in addition to the trauma caused by the operation, irradiation after breast surgery has a significant role in the pathogenesis of fat necrosis (3–9). In the majority of cases, asymptomatic fat necrosis is described by follow-up mammograms and ultrasound (US) examina- tions, as ‘‘post-therapeutic findings’’ or ‘‘postirradiation changes’’ of the treated breast. Usually these findings have no clinical consequences. On the other hand, symptomatic (or clinically evident) fat necrosis includes cases accom- panied by a palpable mass with or without pain, which some- times requires medication or even surgical intervention (10–15). The cautionary article from investigators at Tufts Univer- sity (15) about the high rate of clinically evident fat necrosis after accelerated partial-breast irradiation (APBI) using inter- stitial high-dose-rate (HDR) implants prompted us to review and evaluate the incidence, clinical significance, and possible risk factors of fat necrosis in our patients who were treated within a randomized study with partial-breast irradiation (PBI) or standard whole-breast irradiation (WBI). METHODS AND MATERIALS A total of 258 selected early-stage breast cancer patients with pT1 pN0-1mi, nonlobular breast cancer without the presence of Reprint requests to: Katalin Lo ¨vey, M.D., Department of Radiotherapy, National Institute of Oncology, Ra ´th Gyo ¨rgy u. 7-9, Budapest, H-1122, Hungary. Tel: (+36) 1-224-8600; Fax: (+36) 1-224-8680 E-mail: klovey@oncol.hu Conflicts of interest: none. Received Nov 22, 2006, and in revised form March 26, 2007. Accepted for publication March 28, 2007. 724 Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 3, pp. 724–731, 2007 Copyright Ó 2007 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/07/$–see front matter doi:10.1016/j.ijrobp.2007.03.055