Radiation-induced fibrosarcoma after breast-conserving therapy for breast cancer: a case report and literature review

Abstract

Background

Radiation-induced sarcoma (RIS) has a 10-year incidence of 0.2–0.27% and a poor prognosis, although the radiation should need for breast-conserving surgery. In particular, radiation-induced fibrosarcoma has been rarer, and its incidence is 2.6–3.7% of RIS.

Case presentation

A 43-year-old woman with pT1N1M0 breast cancer underwent breast-conserving surgery, chemotherapy, radiation therapy 8 years ago, and continued hormonal therapy. She complained of a hard unprotruded mass palpated in her right upper outer quadrant of breast. Although we suspected local recurrence, core needle biopsy revealed atypical spindled tumor cells without mammary or epithelial markers. A diagnosis of fibrosarcoma was made via tumorectomy. She underwent additional enlarged surgery.

Conclusions

We report a rare case of fibrosarcoma in breast after breast-conserving surgery and radiation therapy. Fibrosarcoma after radiation therapy for breast cancer has been reported in 30 cases, including the present case. The dead and alive cases were not significantly different in terms of age, primary breast cancer, radiation dose, and following months. Patients with breast masses after radiation therapy should be suspected local recurrence and RIS.

Background

The effects of radiation after breast-conserving surgery absolutely reduce each 10-year recurrence risk or 15-year risk of breast cancer death [1]. However, radiation therapy has also been reported to cause adverse events. Anorexia, malaise, and dermatitis occur in the acute phase. In the sub-acute or late phase, there is pneumonia, cardiotoxicity, anetoderma, and secondary cancer [2, 3]. As secondary cancer, radiation-induced sarcoma (RIS) has a 10-year incidence of 0.2–0.27% [4] and poor prognosis with a 5-year actuarial survival of 36–41% [4, 5]. A collaborative group of early breast cancer trialists reported a ratio of rates of 2.34 (2p = 0.03) of soft-tissue sarcoma after radiation in their meta-analysis [6]. In particular, radiation-induced fibrosarcoma has been rarer, and its incidence is 2.6–3.7% of RIS [4, 7].

We report a rare case of fibrosarcoma after breast-conserving surgery and radiation therapy and review and discuss radiation-induced fibrosarcomas after breast cancer which had been reported.

Case presentation

A 43-year-old Japanese woman visited our outpatient clinic with a right axillary mass. She had a medical history of right breast cancer for 8 years. The primary histology was an 18-mm invasive ductal carcinoma in lower inner quadrant of the right breast with two lymph node metastases, which had hormone receptors and lacked human epidermal growth factor receptor 2 (HER2) amplification. The patient underwent breast-conserving surgery and axillary dissection, diagnosed pathological stage IIA (T1N1M0), and administrated chemotherapy with docetaxel and cyclophosphamide, and radiation therapy (50.0 Gy). During the administration of planned 10-year-tamoxifen and terminated 5-year-luteinizing hormone-releasing hormone agonist, a hard mass of 8.4 mm palpated in her right upper outer quadrant of breast without ulcered and protruded lesions, while no other abnormal findings were identified. Mammography revealed normal breast tissue. We suspected local recurrence of breast cancer. Findings of a core needle biopsy (CNB) revealed a proliferation of fibroblasts, but the lesion was judged to be benign. The lesion had grown for 7 months. After CNB was added, atypical spindled tumor cells without breast cancer markers (hormone receptor, HER2, and FOXA1) and epithelial markers (EMA, E-cadherin, and cytokeratin7, 8, 18, 20, AE1/AE3) were observed. As a mesenchymal marker, vimentin is highly expressed (Table 1, Fig. 1). Radiographic tests were negative for metastasis, ultrasonography scans revealed a 21.3 mm tumor with much vascular flow (Fig. 2a), and magnetic resonance imaging revealed 16-mm irregular geometries close to the skin (Fig. 2b). We decided to perform a tumorectomy to confirm the diagnosis.

Table 1 Immunostaining results for breast, mesenchymal, and epithelial markers

Fig. 1

Pathology of core needle biopsy suspected fibrosarcoma. Core needle biopsy revealed atypical spindled tumor cells (a) with Vimentin expression highly positive (b). Epithelial markers CK7 (c) and E-cadherin (d) are negative

Fig. 2

Ultrasonography and magnetic resonance imaging of the tumor. Ultrasonography scans revealed a 21.3-mm tumor in breast (a). Magnetic resonance imaging revealed 16 mm irregular geometries close to the skin (b)

The pathological diagnosis revealed an 18 mm subcutaneous fibrosarcoma of the adult classic type close to breast (Fig. 3). In addition, skin excision was performed because the surgical margin of the skin was pathologically positive, leading to negative skin margins. The patient received a second opinion at the National Cancer Center Hospital and underwent enlarged excision there.

Fig. 3

Pathology of surgical specimen revealed fibrosarcoma. Atypical spindled cells involved in subcutaneous of HE expression; low-power field (a), high-power field (b)

Discussion and conclusion

The patients performed breast-conserving surgery and radiation had an isolated local recurrence risk reported on 13.1% for 10 years [6], which was higher than RIS incidence. In 1948, RIS was defined as having a history of radiation therapy, occurring in or near the radiation field, and being histologically different from primary cancer [8]. In breast-conserving therapy for breast cancer, angiosarcoma of RIS has the highest reported standardized incidence rations 26.2 [9]. Radiation therapy for breast cancer involves RIS of the chest wall, pleura, and upper extremity [10, 11]. RIS has a poorer prognosis in patients over 60 years, high-grade tumors, and positive margins [5]. RIS in cutaneous was likely to occur as protruded mass and to have relatively a good prognosis [9].

Radiation therapy damages deoxyribonucleic acid (DNA) in exposed cells involved in normal or malignant cells. Fibroblast cell lines repair this DNA damage through histone H2AX phosphorylation in vitro [12]. Although the mechanism of RIS occurrence has not yet been clarified, DNA damage repair might induce some gene variants associated with second malignant neoplasms [13].

We searched the keywords “breast”, “fibrosarcoma, and “radiation” in PubMed in April 2022. We also checked the references cited in the original articles and excluded articles that had no history of radiation therapy, breast cancer and protrubed fibrosarcoma on skin. Thirty cases of radiation-associated fibrosarcoma after breast cancer therapy without protruded cutaneous fibrosarcoma were identified, including our case [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35] (Table 2). All cases were detected based on the patient’s self or physical findings. They were 52.7 ± 10.3 years old, and the duration from primary breast cancer was 9.4 ± 4.9 years (1.3–17 years, median 8.0 years). Within the description, 12 patients (52%) died, and 10 (48%) were alive. RIS also occurred on post mastectomy state. Although the number of cases was small, we compared dead and alive cases using a t-test (Table 3). Not only age, but also duration from primary breast cancer diagnosis, radiation dose, and following months were not significantly different as opposed to prior reports. In recent cases, there might be high accuracy of diagnostic modality and RIS might be detected smaller, diagnosed earlier and lead to more remissions than past cases.

Table 2 Cases of fibrosarcoma after radiation therapy for breast cancer

Table 3 Comparison with cases of dead and alive cases by t-test

Conclusions

Fibrosarcomas after breast-conserving surgery and radiation therapy are rare. Patients with breast masses after radiation therapy should be suspected for not only local recurrence but also RIS.