Angiosarcoma of the breast following surgery and radiotherapy for breast cancer

Abstract

Breast angiosarcoma following surgery and radiotherapy for breast cancer is a rare but important clinical entity. This article reviews all published cases and includes data on incidence, etiology, presentation, diagnosis, management and prognosis. Breast angiosarcoma remains challenging clinically, radiologically and histologically, and thus a high index of suspicion is required in susceptible patients. Surgery is the primary treatment option and there are an increasing number of studies on the use of radiotherapy and chemotherapy, each with variable success. There have been recent reports of patients with metastatic disease responding to taxane chemotherapy, and there might be a future role for targeted agents given the expression of c-KIT in a subset of angiosarcomas. Overall survival, however, remains poor.

Reirradiation and hyperthermia for radiation‐associated sarcoma

“…8 The median latency period ranges from 59 to 103 months in the literature, which is in line with our data. 8,[24][25][26][27][28] RAS may be of any type, but angiosarcoma was the most common in our patient group and in other series of thoracic RAS. [2][3][4]19,22 Angiosarcoma may be associated with chronic lymphedema of a limb or of the chest wall (Stewart-Treves [ST] syndrome), which is diagnosed most frequently after axillary lymph node dissection as a part of breast cancer treatment and can occur in the lymphedematous arm itself or in the shoulder, axillary, or chest wall region.…”

A radiation-induced and radiation-sensitive, delayed onset angiosarcoma arising in a precursor lymphangioendothelioma

“…Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis, and thus may play an important role in the development and progression of angiosarcoma. Studies have suggested involvement of the VEGFR system in the growth and proliferation of hemangiosarcoma cells in vitro (5). Furthermore, it has been reported that positive immunohistochemical staining for VEGF occurs in 14% of primary angiosarcomas and of its 3 known receptors, VEGFR3 has been shown to be present in 50% of all angiosarcomas (5).…”

“…Primary angiosarcomas of the breast generally occur between the ages of 20-40 years and are rare, with an incidence of less than 0.0005% (10). These constitute less than 0.01% of all breast cancers (4,5). Following review of published cases on the subject, Abbott and Palmieri (5) noted that secondary angiosarcomas following mastectomy and radiotherapy presented at a median age of 67 years with a median latency of 72 months between radiotherapy and angiosarcoma development.…”

“…Studies have suggested involvement of the VEGFR system in the growth and proliferation of hemangiosarcoma cells in vitro (5). Furthermore, it has been reported that positive immunohistochemical staining for VEGF occurs in 14% of primary angiosarcomas and of its 3 known receptors, VEGFR3 has been shown to be present in 50% of all angiosarcomas (5). Given the potential involvement of these signalling pathways in the pathogenesis of post-radiotherapy angiosarcoma, it seems reasonable to consider the use of VEGF antagonists such as bevacizumab (humanized monoclonal antibody targeting VEGF-A), sorafenib (an inhibitor of VEGFR1, VEGFR2, VEGRF3 among other receptors) (15), pazopanib (an inhibitor of VEGF2 and VEGF3) (16,17), apatinib (an inhibitor of VEGF2) (18) or even thalidomide (known to suppress VEGF) (19) in the treatment of angiosarcoma.…”

“…Angiosarcomas are one histological subtype of radiationinduced sarcomas, and although a very rare complication, they are significant due to their poor overall prognosis (5)(6)(7). Characterised by rapid proliferation and extensive infiltrating growth, these malignant tumours of the vascular endothelium typically follow an aggressive course with difficulty clearing surgical margins and controlling distant spread.…”