The mean latency period of RAA of the breast after radiation therapy is approximately 5–7 years [3]. Clinically, it presents as violaceous, erythematous plaques; nodes; areas of ecchymosis; and skin thickening [4, 5].
Cahan et al. and Arlen et al. proposed the following criteria for diagnosis of RAA of the breast: (1) a sarcoma arising within the field of previous radiotherapy, (2) differing histology between the secondary sarcoma and primary tumor, and (3) at least a 3-year latency period between radiation therapy and development of the sarcoma [6, 7]. The two present cases fulfilled all of those criteria.
Standard therapy for RAA of the breast is simple mastectomy and/or wide local excision [8], because disease-free survival is significantly shortened if the resected stump is positive for cancer cells [9]. Seinen et al. reported that the cause of high recurrence is due to multifocal growth of angiosarcoma and residual tumor tissue. These investigators reported that even if the surgical margins are considered to be clear, it is preferable to resect all irradiated skin [10]. The suggested treatment is aggressive surgery with removal of the pectoral muscle and subsequent reconstruction to achieve clear margins [11]. For deciding the area of resection, mapping biopsy is useful. Mapping biopsy is multiple skin biopsy at a certain distance from the tumor for detecting tumor invasion. By this method, it is possible to confirm the range of tumor spreading. In case 1, we confirmed the range free from invasion of tumor cells by mapping biopsy, and we resected skin with a 10-cm margin. In case 2, atypical endothelial cells were confirmed both inside and outside of the irradiation range. Atypical post-radiation vascular lesions (AVLs) have been described to arise within previously irradiated skin [12]. Therefore, we considered the possibility of tumor invasion rather than AVLs. Although skin transplantation was required, we were able to resect the tumor completely. Both case 1 and case 2 omitted the axillary operation because there was no metastasis to the axillary lymph node in the preoperative image examination.
Regarding radiation therapy for angiosarcoma, Depla suggested that the addition of reirradiation to surgery may help in local control of RAA [13]. On the other hand, Torres suggested that the use of radiation therapy remains controversial, as repeat radiation exposure to an area that has already been irradiated may result in toxicity [14]. Therefore, we did not perform postoperative radiation therapy for RAA.
Regarding chemotherapy for angiosarcoma, Sinnamon performed retrospective analysis of cutaneous angiosarcoma, and the analysis indicated both adjuvant and neoadjuvant therapy after surgery did not show any survival benefit on univariate and multivariate [15]. On the other hand, there are several reports showing the possibility that taxanes are useful for angiosarcoma [16, 17].
Angiosarcomas express VEGFR [18]. Several studies using anti-VEGF monoclonal antibody have shown antitumor activity in angiosarcoma [19, 20]. On the basis of this background, Ray-Coquard conducted a non-comparative, open-label, randomized phase 2 trial to explore the activity and safety of bevacizumab and paclitaxel therapy for patients with advanced angiosarcoma. Fifty patients were randomized and assigned to two arms: (1) the paclitaxel alone or (2) the paclitaxel and bevacizumab arm. From the findings, they concluded that there is no benefit from adding bevacizumab to paclitaxel [21].
Therefore, it is thought that chemotherapy/molecular target treatment for angiosarcoma has not yet been determined. We used a taxane for two patients, taking into account the fact that the taxane may be effective and that they did not use anthracycline after the initial breast cancer surgery.
In general, the prognosis of patients with RAA of the breast is poor. The 5-year local recurrence-free survival rate is 41–47%, and the 5-year overall survival rate is 10–54% [14, 22, 23]. The median time to local recurrence after diagnosis has been reported to be 6 months (range, 1–89 months) [10, 24]. Poor prognosis is reported to be associated with large tumor size, high histologic grade, and positive surgical margins [25].
To the best of our knowledge, several case reports of RAA in the breast have been published since 1990. In those reports, mastectomy and/or wide excision were conducted; however, no reports have clearly described a method for determination of the surgical margin.
We identified the range of tumor invasion by preoperative mapping biopsy. This technique could potentially lead to complete resection of tumor tissues and a good prognosis.