Early recurrent radiotherapy-induced angiosarcoma post–R0 breast surgery

Patient R had a left wide local excision and sentinel node biopsy for a screen-detected breast cancer at age 63. Histology showed a 25mm invasive breast cancer of no special type, grade 2, hormone receptor positive, human epidermal growth factor receptor 2 negative, no lymphovascular invasion, with 0/7 lymph nodes, giving a final staging of pT2 pN0. Regional breast multidisciplinary meeting (MDM) recommended discussion regarding endocrine therapy, radiotherapy and chemotherapy. The benefit of chemotherapy was deemed to be low (1.3% PREDICT logarithm) and was not pursued.¹ R completed adjuvant radiotherapy to the left chest wall (26Gray in five fractions) and commenced letrozole.

Two years following radiotherapy, R presented with petechial bruising over her left chest wall. Punch biopsy showed angiosarcoma. She had further radiological investigations, including a staging computed tomography (CT) scan, magnetic resonance imaging (Figure 1) and fluorodeoxygenase positron emission tomography. These detected a pulmonary embolus, for which she was started on rivaroxaban, and multiple small lung nodules that had a benign appearance.

View Figure 1–3.

R proceeded to a left mastectomy with latissimus dorsi flap and split skin graft at a specialist sarcoma centre. Histology showed a 210x150x5mm-deep angiosarcoma with widely clear margins. Immunohistochemistry studies with positive cell markers, such as c-Myc, favoured radiation-induced angiosarcoma (RAAS) rather than primary angiosarcoma. Given these findings, sarcoma MDM concluded that no further treatment was required.

Three months later, new petechial skin changes developed over the surgical site (Figure 2). Punch biopsy confirmed angiosarcoma recurrence.

Repeat scans showed new pulmonary nodules, suspicious for metastases. R had wider excision of the left posterior chest wall area with 5cm margins deep to muscle and fascia, and split skin grafting (Figure 3). Histology showed further multifocal angiosarcoma over an area of 185x110x50mm, with microscopic disease present at deep margins.

Any further surgery now would require extensive chest wall reconstruction with significant associated morbidity. It was agreed that this would not be appropriate, and R was referred to medical oncology to discuss suppressive systemic treatments. She has completed palliative chemotherapy with paclitaxel. Her last CT scan, 7 months after her last operation, showed stable disease.

Discussion

RAAS is a rare but severe complication of radiotherapy with an incidence rate of about 0.05–0.3% in patients who have had treatment after breast-conserving surgery.¹ It carries a poor prognosis, with a reported 5-year mortality of 32%.^2,3 Pathogenesis of the disease appears to be related to a combination of factors, including radiation-induced DNA damage and lymphoedema.²

Initial presentation of RAAS can include a petechial rash, skin thickening or nodules over the area directly exposed to radiation. However, this can have a latency period of more than a decade following radiotherapy completion, with a median latency time of 6–11 years.⁴ Tissue biopsy is vital for diagnosis. This particular case is significant in that R presented within 2 years post-radiotherapy with cutaneous symptoms.

While a wider excision or mastectomy to clear margins is generally accepted, it is not always adequate to prevent local recurrence. Other approaches have suggested complete resection of all irradiated tissues to prevent local recurrence.⁵ Despite achieving R0 resection on mastectomy, R still developed early local recurrence with progressive metastatic disease. This may be related to initial tumour seeding at time of index excision, prior radiotherapy-induced tissue changes or the multifocal infiltrative nature of RAAS.⁶ Current literature debates the role of neoadjuvant chemotherapy, with few case reports suggesting improvement in achieving R0 resection.⁶ RAAS remains a challenging disease to manage and treatment requires close collaboration with specialist sarcoma services.

Learning points

• RAAS can present as early as 2 years following treatment and is a rare but significant complication post breast radiotherapy.
• Surgical management of RAAS may not always be successful and local recurrence can still occur despite widely clear margins.