Radiation-induced sarcoma of the breast: a systematic review

Abstract

Introduction: Radiation-induced sarcoma (RIS) is a rare, aggressive malignancy. Breast cancer survivors treated with radiotherapy constitute a large fraction of RIS patients. To evaluate evidenced-based practices for RIS treatment, we performed a systematic review of the published English-language literature.

Methods: We performed a systematic keyword search of PubMed for original research articles pertaining to RIS of the breast. We classified and evaluated the articles based on hierarchical levels of scientific evidence.

Results: We identified 124 original articles available for analysis, which included 1,831 patients. No randomized controlled trials involving RIS patients were found. We present the best available evidence for the etiology, comparative biology to primary sarcoma, prognostic factors, and treatment options for RIS of the breast.

Conclusion: Although the evidence to guide clinical practice is limited to single institutional cohort studies, registry studies, case-control studies, and case reports, we applied the available evidence to address clinically relevant questions related to best practice in patient management. Surgery with widely negative margins remains the primary treatment of RIS. Unfortunately, the role of adjuvant and neoadjuvant chemotherapy remains uncertain. This systematic review highlights the need for additional well-designed studies to inform the management of RIS.

Conflict of interest statement

Disclosures: Grishma R. Sheth: None; Lee D. Cranmer: Threshold Pharmaceuticals (C/A); Merck, Altor, Amgen, Genentech, Roche, Gerson Lehrman Group (H); Supergen, Threshold, Biovex, Bristol Meyers Squibb, Progen, Ziopharm (RF); Benjamin D. Smith: UT MD Anderson Cancer Center (E); Varian Medical Systems (RF); Lauren Grasso-LeBeau: None; Julie E. Lang: Genomic Health (H); Sysmex Corp (RF).

Section Editors: Laurence Baker: BioMed Valley Discoveries, Merck (C/A); Jaap Verweij: None.

Reviewer “A”: None

Figures

Figure 1.

Histologic micrograph of a radiation-induced sarcoma (RIS) of the breast. This image shows a radiation-induced malignant fibrous histiocytoma displaying a storiform growth pattern with highly atypical (often bizarre) neoplastic cell nuclei. This histologic image of RIS shows a striking low-power appearance as a result of cellularity, a vague whorled pattern, and marked nuclear atypia. The patient, a 52-year-old woman with ductal carcinoma in situ, was treated with breast-conserving surgery and adjuvant radiotherapy of 5,000 Gy. Six years later, she returned with a lump at her lumpectomy site; an incisional biopsy revealed atypical spindle-cell fibroblast proliferation consistent with a radiation-induced secondary malignancy.

Figure 2.

Magnetic resonance imaging (MRI) scan of a radiation-induced sarcoma (RIS) of the breast. A breast MRI scan shows gadolinium in a patient with RIS. Tumor involvement with the chest wall is present. Bulky residual disease is demonstrated between 9 o'clock and 12 o'clock along the posterior margin of the seroma cavity and at 6 o'clock on the inferior margin of the seroma cavity 18 mm from the chest wall. The more posterior residual disease directly infiltrates the pectoralis major muscle.

Figure 3.

Radiation-induced angiosarcoma. (A): Radiation-induced angiosarcoma occurring in a patient previously radiated after mastectomy. (B): Radiation-induced angiosarcoma occurring in a patient previously radiated after lumpectomy. Photos courtesy of Dr. Chan Raut, M.D., Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.