# Radiation-Induced Leiomyosarcoma after Breast Cancer Treatment and

Authors: M. Olcina; B. Merck; M. J. Giménez-Climent; S. Almenar; M. F. Sancho-Merle; F. Llopis; C. Vázquez-Albadalejo
Journal: Sarcoma
 (2008)

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## Abstract

The development of a radiation-induced sarcoma (RIS) in the post mastectomy thoracic treatment volume is an infrequent, but recognized, event. Its frequency is rising in relation with increasing survival of breast cancer patients treated with adjuvant radiation therapy, and is associated with poor prognosis despite treatment.
We present a case of leiomyosarcoma in a patient who underwent mastectomy followed by radiotherapy for invasive ductal carcinoma. A delayed TRAM flap reconstruction was performed 10 years after and a rapid growing mass under the reconstructed flap appeared, on routine follow-up, twenty years later. This report analyzes the diagnostic and therapeutic approach of patients with RIS.


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## Body

## 1. Introduction

The increasing survival rate in breast cancer patients makes meticulous long-term
follow up of secondary adverse effects of the used therapies necessary.
Adjuvant radiotherapy to the breast plays a significant role in preventing
local failure after mastectomy in advanced disease [1]. The development of
secondary neoplasm is of particular importance, especially sarcomas in women
previously treated with radiation therapy [2]. Case reports [3, 4] and the publications of large series of
important oncology centers [5] or registers [6] is a consequence of the increasing frequency of
this type of secondary neoplasms.Leiomyosarcoma is the more prevalent sarcoma category occurring after
breast cancer in the Surveillance, Epidemiology and End Result (SEER) data [5],
although most published reports describe angiosarcoma as the most frequent
histological entity following breast conservation and radiation therapy [3].Surgical approach is the usual management of these neoplasms, but it is
not always possible because of tumor size and localization. After revision of
international databases, the authors have not found any case report about a
RIS developing subsequent to delayed TRAM flap breast reconstruction.


## 2. Case Report

We present a 57-year-old women diagnosed in 1986 of a multicentric
invasive ductal carcinoma of the right breast. Histological examination of
modified radical mastectomy, done as the initial treatment, showed a notable
axillary extension with nineteen of twenty-five lymph nodes positive for cancer
and extracapsular rupture. Standard extension exams were negative for
metastases. She received postoperative chemotherapy consisting of 5 cycles of
adriamycin plus cyclophosphamide. Afterwards, radiation therapy was delivered
on right thoracic wall, internal mammary nodes, supraclavicular fossa, and
axilla at a total dose of 50 Gy and a 10 Gy boost on mastectomy scar.Eleven years after, delayed reconstruction was carried out using a
double-pediculated TRAM flap, with a good cosmesis and contralateral symmetric
result.Seven years after reconstruction and twenty years after primary
treatment, the patient noticed a progressive growing of the reconstruction flap
in the foregoing month, and the appearance of a bad limited, itching, and hard
area on the reconstructed breast. Physical exam showed a tumor of about 15 centimetres, fixed to the thoracic wall and suggestive of tumor failure.Magnetic resonance imaging revealed a tumor (13×16×10 centimetres)
located on the right breast area, infiltrating to a large extent the
myocutaneous flap and the adjacent costal wall, mostly on the inferior border
(Figures 1(a) and 1(b)). The biopsy demonstrated a tumor composed of fascicles
of elongated spindle-shaped cells with eosinophilic cytoplasm and blunt-ended
(cigar-shaped) nuclei. Some pleomorphic, multilobulated malignant cells were
reported. Immunohistochemical staining showed similar cellular features and the
presence of smooth muscle actin in the cytoplasm (Figures 2(a)
and 2(b)).(a) MRI: tumor growth on right breast area. (b) MRI: myocutaneous flap infiltration.
(a)(b)(a) HE staining: fascicles of elongated
spindle-shaped cells. (b) Immunohistochemical staining: presence
of smooth muscle actin in the cytoplasm.
(a)(b)Primary systemic treatment was suggested because of large thoracic
extension of the sarcoma, in the intention of reducing tumor size and limiting
the neoplasm, making it affordable to surgical treatment. The patient received
five courses of ifosfamide and clinical progression
was evidenced by thoracic CT scan. A docetaxel with gemcitabine combination was
proposed. The patient died after the second course.


## 3. Discussion

Radiation-induced leiomyosarcoma of the breast seems to become
increasingly common, with patients being diagnosed years after the radiation
therapy, as survival of these women is enhanced because of multimodal
treatment. The cumulative RIS incidence is 0.07% (±0.02) at 5 years, 0.27% (±0.05) at 10 years, and 0.48% (±0.11) at 15 years. The standardized incidence
ratio (SIR) is 10.2 (95% CI, 9.03–11.59) for the irradiated population
compared with the general population and 1.3 (95% CI, 0.3–3.6) for patients
with breast carcinoma who did not receive radiotherapy with the general
population’s risk, as the data of the largest published paper [5]. These results
are similar to those published by Taghian et al. in their study about eleven
radiation induced sarcomas in 6919 irradiated patients [7]. The Instituto
Valenciano de Oncología has previously reported a RIS in a woman after breast
conserving therapy [4].RIS diagnosis is done using the criteria established by Cahan et al.: (1)
record of radiation therapy, (2) asymptomatic latency period of several years,
(3) occurrence of sarcoma within a previously irradiated field, and (4)
histologic confirmation of the sarcomatous nature of the neoplasm [8, 9].Clinical features include patients with a complete remission of the primary
tumors, the latency period fluctuating between 3 and 20.3 years before the
secondary sarcoma grows [10]. The patient described
in this report was tumor free twenty years after primary
treatment. A tumor developing in the irradiated volume years after radiation
treatment should raise suspicion about a radiation-induced sarcoma. Wide
excision and pathological exam are recommended to confirm the suspicion [11].
We have performed a percutaneous biopsy, because the large tumor extension and
costal wall infiltration made primary surgical excision impossible.In the experience of SEER of 274.572 breast cancer patients diagnosed
between 1973 and 1996, the most prevalent sarcoma category occurring after
breast cancer was leiomyosarcoma (22.1%), followed by malignant fibrous
histiocytoma (15.2%), angiosarcoma (13.7%), and liposarcoma (8.7%) [6]. The
Institut Curie clinical practice about 16705 breast cancer patients shows
angiosarcoma as the most frequent histologic subtype (48%) [10].
Different staining with immunohistochemical procedures permits a correct
histological differentiation. Biopsy staining with immunoperoxidase shows the
presence of vimentin and smooth muscle actin in the cytoplasm of leiomyosarcoma
[12].Usual therapeutic management includes wide surgical resection to obtain broad tumor
free margins. RIS is often located in anatomic areas that preclude radical
surgery, and diagnoses in advanced disease rules out surgical management, as
happened in our patient. In our case, extensive costal wall extension excluded
surgery and primary chemotherapy was intended with the aim of reducing tumor
burden and allowed radical excision. As tumor progression developed after
chemotherapy, surgery was discarded.Experience described with systemic treatment has been disappointing, obtaining a small
number of clinical responses. Kuten published, in 1985, the results of seven
patients with RIS after irradiation for breast cancer, treated with standard
four-drug combination. All 7 patients died within six to 36 months after RIS
diagnosis [13]. Most authors did not found any evidence of benefit after
chemotherapy in RIS patients [3].This case report points out the need for a careful follow-up for breast cancer patients,
because of the possibility of secondary tumors, not only local failures or
contralateral tumors, but also treatment related. If an RIS is suspected, the
correct way for quick diagnoses includes a CT scan and a magnetic resonance
imaging, in association with a core biopsy and detailed immunohistochemical
analysis. Surgical treatment, if possible, offers the best treatment option.



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