1. The Incidence of Radiotherapy-induced Angiosarcoma of the Skin After Treatment for Breast Cancer in Denmark. A Population-based Study Katalin Kiss1, Simon Andreasen1, Maj-Lis Møller Talman1, Søren Daugaard1, Thomas Mentzel2
1Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Denmark, 2Dermatopathology, Friedrichshafen, Germany
ABSTRACT
METHODS
RESULTS
Background: Angiosarcomas (AS) of the skin are seen in three clinical settings: 1) UV-induced AS after long-term sun exposure, 2) in chronic lymphedema and 3) following radiotherapy (RT). Adjuvant RT after breast-conserving surgery (BCS) has increased through recent years, but the exact incidence of RT-induced AS in women treated for breast cancer is unknown.
Design: Data from all women diagnosed and treated for breast cancer in Denmark, in the period were identified in the national database of the Danish Breast Cancer Group (DBCG). In the same time period, AS cases in the breast region were identified by searching the Danish National Pathology Database.
Results: Forty-three cases of AS in the breast were identified, of which 40 (93%) occurred within 10 years after RT. This allows us to calculate the incidence of RT-induced AS in the first 12 years of the study period with a 93 % probability. The incidence of RT-induced AS was found to be 0.27%. In addition, 7 other types of sarcomas were identified in the same population giving a total incidence of RT-induced sarcomas of 0.32%.
Conclusion: The incidence of angiosarcomas in Danish women treated with RT for breast cancer over a period of 12 years is 0.3%.
All women (78,881) diagnosed with breast cancer in Denmark in the period of were identified from The Danish Breast Cancer Group (DBCG) registry. The DBCG database includes detailed treatment and follow up data on patients with no previous malignancies treated with curative intent (50,616 patients), Fig. 2. Of these, 33,921 patients received adjuvant RT and 11,110 had up to 10 years follow-up. Angiosarcoma cases in the breast region were identified from the Danish National Pathology Database. The radiation dose, fractions and time (48 Gy/24fx/4½ weeks) were not changed in the period3.
Forty-three cases of secondary AS of the breast were identified in the 21 year period; 40 of them developed within 10 years after RT. Thirty-five patients were included in the DBCG database and 29 had at least 10 years follow up. Eighteen of the AS only involved the skin, 9 involved both the skin and the breast parenchyma and 2 were parenchymatous only.
Twenty eight patients were treated with BCS and RT, one with mastectomy and RT because of axillary node metastasis.
Seven other types of sarcomas were identified in the same population giving a total incidence of RT-induced sarcomas of 0.32%.
None of the 16,695 patients who did not receive adjuvant radiotherapy developed secondary sarcomas.
Figure 4. Interval between RT and diagnosis of
angiosarcoma in years.
OBJECTIVES
CONCLUSIONS
Figure 2. All Danish women diagnosed with breast cancer in a 21-year period. The DBCG database includes only women with no previous history of malignancy. Due to the known latency of AS following RT, only patients with a minimum of 10 years follow-up were included for further study.
Breast cancer is the most frequent malignancy among Danish women. The introduction of breast-conserving surgery (BCS) in the management of breast cancer has resulted in a 5 fold increase in the use of adjuvant RT for this large group of patients, in the study period (Fig.1). Radiotherapy-induced AS is a serious complication of which the extent is unknown1,2. The aim of this study is to determine the incidence of secondary AS in Danish women treated for breast cancer with RT.
The incidence of secondary angiosarcomas in Danish women treated with RT for breast cancer is 0.3%.
The vast majority (93%) of RT-induced AS occur within 10 years following breast cancer treatment.
Planning radiation therapy aims to assure minimal radiation dose to the lung and heart and giving the optimal coverage of the target, but it may lead to an increase of the cutaneous radiation dose. The incidence of RT induced AS is not only dependent upon the number of radiation treated patients, but also upon the received cutaneous radiation dose. These parameters has to be taken into account when predicting the incidence of secondary AS in the future. A B
Figure 3: (A) Mastectomy specimen from a 73 y.o. woman, treated five years previously for BCS and RT for a 14 mm, gr.2 invasive ductal carcinoma with nodal metastases. She had cutaneous thickening and some discoloration for 6 months prior to surgery. (B) HE slide of the tumor showing anastomosing vascular structures lined by highly atypical endothelial cells with atypical mitosis (black arrow). Note the endothelial multilayering.
REFERENCES
Mentzel T, Schildhaus HU, Palmedo G, Büttner R, Kutzner H. Postradiation cutaneous angiosarcoma after treatment of
breast carcinoma is characterized by MYC amplification in contrast to atypical vascular lesions after radiotherapy and
control cases: clinicopathological, immunohistochemical and molecular analysis. Mod Pathol 2012;25(1):75–85.
2 Flucke U, Requena L, Mentzel T. Radiation-induced Vascular Lesions of the Skin: An Overview.
Adv Anat Pathol 2013;20(6):407–15.
Overgaard M, Christensen JJ. Postoperative radiotherapy in DBCG during 30 years. Techniques, indications and clinical
radiobiological experience. Acta Oncol. 2008;47(4):639-53
Figure 1: The increased no. of patients in 2009 is a result of the introduction of nationwide organized mammography screening.