Refractory Angiosarcoma of the Breast with VEGFR2 Upregulation Successfully Treated with Sunitinib

Secondary angiosarcoma of the breast is a rare, but well-described complication of radiation therapy for primary breast carcinoma. Currently, it appears refractory to most systemic chemotherapy though rare responses to taxanes exist (1,2). Overall, patient prognosis is poor (3). A 78-year-old female underwent left breast conservation and axillary node dissection in 1999 for invasive ductal carcinoma followed by whole breast radiation therapy. Eleven years later, she noted multiple small nodules in the medial aspect of the left breast. Biopsy of the nodules revealed angiosarcoma of the breast. A metastatic follow-up showed no evidence of distant disease and a modified radical mastectomy performed. Histopathology confirmed the presence of angiosarcoma with all margins negative. The patient completed a course of postmastectomy irradiation with dose limitation by previous radiation for her original breast conserving procedure. This was administered concurrently with adjuvant chemotherapy (Taxol and Adriamycin). The patient did not tolerate the chemotherapy but finished the course of radiation therapy. Ten months later, angiosarcoma nodules recurred along the mastectomy scar. Chemotherapy with single agent carboplatinum was ineffective. Six months later, she underwent a wide resection of the skin and soft tissue of the left chest wall with multiple cutaneous nodules and positive deep margin (the pectoral muscle/ribs) was noted. In the interim, she underwent a split thickness skin graft to cover the large defect. Within 6 months, recurrent disease appeared in the graft and surrounding soft tissue. With no documented distant metastases, the patient again underwent a resection of recurrent tumors, chest wall and two ribs requiring TRAM flap coverage. A Caris profile was requested. She remained free of local recurrence for only 4 months, when multiple and rapidly growing subcutaneous nodules became evident about the chest wall and flap (Fig. 1A). The Caris gene expression assay performed earlier demonstrated a potential therapeutic benefit of sunitinib due to the upregulation of VEGFR2. Sunitinib was then