• © 2007 by American Society of Clinical Oncology

Complete Response From Thalidomide in Angiosarcoma After Treatment of Breast Cancer

A 75-year-old woman had radical mastectomy for left breast carcinoma (pT2N0M0) in 1985. She did not receive any adjuvant treatment. Ten years later, she developed contralateral breast cancer (pT2N2M0), for which she underwent wide local excision with axillary clearance followed by adjuvant radiotherapy to the whole breast (50 Gy, 25 fractions over 5 weeks), with interstitial brachytherapy boost (24 Gy at a rate of 0.54 Gy per hour) to the tumor bed. She received adjuvant tamoxifen for 5 years because of estrogen receptor positivity. Apart from the development of mild lymphedema in the right arm, the follow-up remained uneventful until May 2006 when she noticed several painless bluish nodules of varying size (1.5 to 3.0 cm in diameter) on the medial aspect of her right arm and along the scar. Clinically, the possibilities of recurrent breast cancer versus angiosarcoma were considered, and all lesions were excised with wide margins. Histopathologic evaluation revealed high-grade epitheloid angiosarcoma (Fig 1). Tumor cells were positive for CD34 (Fig 2). The patient was started on radiation therapy (interstitial brachytherapy followed by external-beam radiation therapy). While on radiotherapy, seven or eight new lesions reappeared on the breast and the right arm, including new lesions within the radiation field measuring 2 to 3 cm in diameter (Fig 3A). Repeat excision biopsy reconfirmed the diagnosis of angiosarcoma. Considering the patient's advanced age and the questionable efficacy of chemotherapy, she was offered thalidomide. This therapy was started at a dose of 200 mg/day. To our surprise, all the lesions responded dramatically to the treatment and she achieved clinical complete response in 4 weeks (Fig 3B). She developed pruritis and dryness of skin, which are known side effects of thalidomide, and the dose was reduced to 100 mg/day at 8 weeks. Eight weeks after reducing the thalidomide dose to 50 mg, disease recurred in two nodules. The thalidomide dose was increased to 200 mg, which brought about disease stabilization.

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Fig 1.

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Fig 2.

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Fig 3.

Angiosarcoma is an aggressive malignancy of endothelial origin with varying etiology that is idiopathic, occurs after radiation therapy, and is associated with lymphedema.¹ Incidence of primary angiosarcoma of the breast is approximately 0.01% of all breast cancers.^2,3 Over the years, with improvement in radiation and surgical techniques, the occurrence of what is also known as Stewart-Treves syndrome has become a rarity. In contrast, radiation-induced angiosarcoma is being diagnosed more often in patients who have undergone breast-conservation therapy.⁴ The median time interval between breast-conservation radiotherapy and diagnosis of angiosarcoma is 68 months (range, 12 to 192 months).⁴ Because of variable nonspecific appearances and a lack of clinical suspicion, diagnosis is often delayed. Owing to the rarity of the disease there are no treatment guidelines. Conventionally, it has been treated by complete surgical excision with wide margins. Adjuvant radiation can be used depending on the last dose of radiotherapy. Use of systemic chemotherapy is largely palliative and is limited to case reports.⁵ The estimated 3-year overall survival for this subgroup of patients is only 20%.⁴ Our case qualifies for the diagnosis of radiation-induced angiosarcoma per Cahan's criteria.⁶ The reappearance of lesions on radiotherapy was ominous. Thalidomide was chosen because of its antiangiogenic effects and known therapeutic efficacy in Kaposi's sarcoma. To the best of our knowledge, thalidomide has not been used previously in radiation-induced angiosarcoma. Thalidomide has shown response in three case reports: in a patient with metastatic small-intestine angiosarcoma,⁷ in canine hemangiosarcomas,⁸ and in a patient with chemoresistant metastatic angiosarcoma that resulted in stable disease.⁹ We plan to continue maintenance therapy at a dose of 50 mg daily for the foreseeable future. Our case highlights the potential of thalidomide in another condition hitherto unknown, and raises the possibility of its use in other closely related conditions.