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76-year-old woman presents with purple spots on her chest
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Our patient was a 76-year-old woman who presented to her primary care physician with complaints of purple spots on her right chest. She reports that she was diagnosed with stage-I infiltrating ductal carcinoma involving the right breast in 1998. She underwent breast-conserving treatment for a pT1N0M0 infiltrating ductal carcinoma followed by external beam radiotherapy using medial and lateral tangents with 6 MV photons to 50.4 Gy. She subsequently received five years of adjuvant tamoxifen. She had done well without any evidence of recurrent breast cancer for the next three years.
Upon presentation to her primary care physician eight years after her breast cancer diagnosis, she complained of thickening over the outer quadrant of her right breast, as well as some mild discoloration of the skin. She denied any nipple discharge, any chest wall pain or axillary adenopathy. She was feeling well without any other significant complaints.
The patient’s past medical history was significant for an ovarian cyst requiring a unilateral oophorectomy at age 40, a hysterectomy, osteoarthritis and intermittent depression. She was not taking any medications at the time of presentation.
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Source: A. Blaes |
She was a retired emergency department nurse who did not smoke or drink alcohol. She lived with her daughter who is a lymphoma survivor.
Physical examination showed that the patient was well developed and well nourished. She appeared healthy. Her heart, lungs and abdominal exam were unremarkable. Her left breast had no evidence of masses, nipple discharge or axillary adenopathy. The right breast had no nipple discharge. There was a large area of increased thickening with slight purplish discoloration at the 6 o’clock position of her right breast. An incisional biopsy initially revealed atypical vascular proliferation. Secondary review of the pathology confirmed a high-grade angiosarcoma involving the skin.
What is the most appropriate therapy for this patient?
A. Surgical resection with a mastectomy of the right breast.
B. Radiation therapy.
C. Chemotherapy with paclitaxel.
D. Clinical trial enrollment.
CASE DISCUSSION
Soft tissue sarcomas are rare malignancies, occurring in less than 1% of all cancers. Some studies suggest that they occur with an incidence rate of two cases per 100,000 individuals per year. Although most cases occur without any identifying etiologic factor, there are a small proportion of cases that appear to be attributable to ionizing radiation. What is most troublesome in these cases is the fact that these aggressive tumors occur iatrogenically.
Radiation-induced cancers were first identified by Beck in 1922. Radiation doses greater than 50 Gy cause cell death; those at lower levels induce cellular and DNA damage. It is hypothesized that the repair mechanisms are damaged at these lower levels of radiation. The survivability of these cells with genetic mutations may then progress to tumor development.
In general, these tumors tend to be aggressive and to recur. Neuhaus et al reviewed their institution’s experience and identified 67 cases of radiation-induced cancers. The most common indication for radiation was breast cancer. The median interval from irradiation to the development of a radiation-induced sarcoma was 11 years (range three to 36). Median tumor size was 7 cm, with 56% being high grade at the time of diagnosis. The most common subtype in breast cancer survivors is a lymphangiosarcoma, suggesting that both radiation and the presence of lymphedema may be associated with the development of radiation-induced sarcomas. Clinical findings at the time of presentation most commonly include pain, mass and skin discoloration.
The most important management of these patients is surgical resection with negative margins. It is the only curative option. On average, the median sarcoma-specific survival is 54 months with five-year sarcoma specific survivals of 41% to 45%. The role of adjuvant radiation therapy in this setting is not well understood. Because most of these patients have received prior radiation therapy, they are typically not candidates for additional radiation treatment. Although adjuvant chemotherapy appears useful in childhood sarcomas such as extraskeletal Ewing’s sarcomas, it does not appear to have a role in this type of sarcoma.
The risk of local recurrence appears to be about 65%. The biggest predictor of relapse is the presence of positive surgical margins. At the time of recurrence, additional surgery and possibly radiation therapy are the treatments of choice. Systemic chemotherapy has been tried with varying degrees of success. Chemotherapeutic agents with activity in angiosarcoma include anthracyclines, ifosfamide, gemcitabine, taxanes and more recently the molecularly targeted agents sunitinib (Sutent, Pfizer) and bevacizumab (Avastin, Genentech).
The ANGIOTAX study evaluated the utility of paclitaxel 80 mg/m2 on days one, eight and 15 on an every 28 day cycle. In this study, 30 patients were treated, and resulted in a progression-free survival at two and four months of 74% and 45%. With a median follow-up of eight months, the median time to treatment progression was four months, with an overall survival of eight months. Based on these results and those of additional studies, paclitaxel or doxorubicin are recommended first-line agents for angiosarcomas. Enrollment in a clinical trial would also be an ideal option.
Our patient was treated with a right mastectomy with a local flap reconstruction. Pathology revealed a high-grade angiosarcoma involving the skin, subcutis and breast parenchyma. The angiosarcoma measured 10 cm in greatest diameter with involvement of the nipple and areola. She unfortunately developed a recurrent reddish mass a few months later medial to the mastectomy scar; a biopsy proved to be recurrent angiosarcoma. She was treated with paclitaxel chemotherapy for 12 weeks followed by hyperfractionated radiation therapy. She developed additional nodules along her chest wall (figure 1). Over the next 18 months, she was treated with liposomal doxorubicin, gemcitabine, sunitinib, ifosfamide and vinorelbine. She continued to progress with an increasingly large number of nodules across her chest wall that resulted in bloody discharge and pain. Despite multiple attempts at treatment, the patient failed to respond and subsequently enrolled in hospice therapy and died.
Anne H. Blaes, MD, is a Fellow at the University of Minnesota and a member of the HemOnc Today Editorial Board.
For more information:
- Ann Surg. 2004;239:903-910.
- Eur J Surg Oncol. 2008 (epub ahead of print).
- J Clin Oncol. 2008;26:5269-5274.