Radiation Therapy For Breast Angiosarcoma

Introduction

Definition and Overview

Angiosarcoma of the breast is a rare condition, accounting for 1% of all malignant (invasive) breast cancers. It can be classified as primary or secondary, the latter being more common in those who have previously had radiation therapy for breast cancer and is associated with persistent lymphoedema. Both show clinically as large, rapidly spreading tumours.

Surgery is the primary form of treatment because it gives the most effective local control, whereas radiation and chemotherapy can be less effective and have more side effects.¹ The term "angiosarcoma" describes two Greek words that mean vessel (angios) and flesh (sarcoma), describing a sarcoma subtype that begins in vessels and spreads to other organs. Its cells demonstrate properties identical to endothelial cells in the breast, liver, heart, spleen, soft tissues, and bone. Angiosarcoma ranges in histology from a distinct tumour to a high-grade spindle cell cancer.²

Importance of radiation therapy

Radiation therapy is critical in the treatment of breast angiosarcoma, a rare and aggressive cancer that arises from the blood vessels of the breast. This therapy technique offers a few important benefits in the management of breast angiosarcoma. First and foremost, radiation treatment is successful in controlling local tumours. It can identify and eliminate cancer cells in breast tissue, even those that have migrated to neighbouring lymph nodes or other organs. This localised method aids in preventing disease transmission and reducing the danger of local recurrence.³

Furthermore, radiation therapy is frequently used as an additional treatment after surgery, which is known as adjuvant radiation therapy. Breast angiosarcoma has a strong tendency for local recurrence even after full surgical excision. Adjuvant radiation treatment reduces the likelihood of local recurrence and increases overall survival rates. Radiation therapy can also be used as a neoadjuvant procedure before surgery. It may aid in tumour shrinkage, making surgical resection more possible, and perhaps improving the likelihood of establishing clean surgical margins. Several studies have found that radiation treatment is effective in treating breast angiosarcoma. Adjuvant radiation treatment, for example, was linked to enhanced local control and healthy rates of survival in research by Italiano et al. (2010). Kim et al. (2016) discovered that neoadjuvant radiation treatment was beneficial in downstaging the tumour and boosting the rate of full surgical resection.⁴

Understanding breast angiosarcoma

Aetiology and risk factors

Breast angiosarcoma has a complex set of causes. One of the most important risk factors for breast angiosarcoma is prior radiation therapy. Patients who have had chemotherapy or radiation therapy for breast cancer or other malignancies have a greater likelihood of developing angiosarcoma in the radiated area. The specific method by which radiation causes angiosarcoma is unknown; however, it is assumed that it involves DNA damage and changes in the microenvironment.⁵

Furthermore, inherited factors may contribute to the growth of breast angiosarcoma. In some cases, angiosarcoma has been linked to inherited genetic illnesses such as hereditary retinoblastoma, Li-Fraumeni syndrome, and vascular abnormalities such as Klippel-Trenaunay syndrome.⁶ These genetic anomalies may contribute to angiosarcoma development by interfering with normal cell cycle control and vascular development. Additionally, chronic lymphoedema, exposure to environmental pollutants, and hormonal impacts have all been mentioned as potential contributors.⁷

Clinical presentation and diagnosis

Breast sarcoma is an uncommon form of tumour that develops from the breast's connective tissue or stromal cells. It frequently manifests itself as a painless, quickly developing tumour or lump in the breast. Skin changes, nipple retraction, and palpable axillary lymph nodes (around your armpit) are all possible clinical findings.

Breast sarcoma is diagnosed using a mix of clinical evaluation, imaging investigations, and pathological testing. They can be difficult to detect since they might resemble benign breast tumours or cancer. Diagnostic imaging procedures such as mammography, ultrasound, and magnetic resonance imaging (MRI) can help determine the size of a tumour. However, a biopsy must be performed for an exact diagnosis, involving extracting a tissue sample from the lump for histological evaluation. To get an acceptable tissue sample, a core needle biopsy or incisional/excisional biopsy is usually used. A skilled pathologist must do a histopathological investigation to establish the diagnosis of sarcoma and define its subtype, grade, and amount of invasion.⁸

Staging and prognostic factors

The stage of breast angiosarcoma generally depends on tumour size, lymph node involvement, and the evidence of distant metastases (spread to other parts of the body). There is, however, no commonly approved staging classification for breast angiosarcoma. Tumour size, histological grade (based on findings from microscope analysis), lymph node involvement, surgical margin status (whether the whole tumour was removed in surgery), and metastasis are all prognostic variables. A poor prognosis is related to lymph node metastases (spread) and incomplete removal of the full tumour. 

Role of radiation therapy

Rationale and goals

The primary objective of radiation therapy in the treatment of breast angiosarcoma is to establish local tumour control while lowering the chance of recurrence. In instances where surgical resection is not possible or complete, radiation therapy plays an important role in treating it. It can aid in tumour shrinkage, symptom relief, and regional management by targeting the remaining tumour cells in the affected region. The objective of radiation therapy for patients with breast angiosarcoma is to destroy or manage the tumour locally, maintain organ function, and improve overall results.⁹

Patient selection criteria

After surgical removal of the tumour, radiation treatment may be used to lower the possibility of local recurrence, especially if it is not possible to remove the whole tumour. In some circumstances, radiation treatment may be used before surgical resection to reduce the tumour size and allow for a more successful surgical excision. In situations of advanced or metastatic breast angiosarcoma, radiation treatment can also be utilised to relieve symptoms and enhance the quality of life.¹⁰

Techniques and modalities

External beam radiation therapy (EBRT)

External beam radiation therapy (EBRT) is a popular treatment option for many cancers, including breast angiosarcoma. EBRT uses linear accelerator equipment to administer radiation to the cancer spot from outside the body. It is usually given in a series of sessions over several weeks, each lasting a few minutes. The goal of EBRT for breast angiosarcoma is to eliminate leftover cancer cells, lower the chance of local recurrence, and enhance overall survival. It is also frequently used as an adjuvant therapy after surgical resection or as a palliative treatment to alleviate symptoms in advanced or metastatic instances. The specific dose of radiation, fractionation schedule, and treatment volume are selected depending on the features of the individual patient as well as the location and extent of the tumour. Radiation oncologists determine the treatment plan, which is carried out by a radiation therapy team.¹¹

Brachytherapy

Brachytherapy is a form of radiation therapy in which radioactive sources are inserted into or near the tumour location. It is used to treat a variety of malignancies, including breast cancer. Brachytherapy provides a high dosage of radiotherapy to the tumour while exposing as few healthy tissues as possible.¹²

Radiation induced angiosarcoma

Overview and incidence

Radiation-induced angiosarcoma (RIAS) is a rare and severe malignant tumour that develops from blood vessel endothelial cells, frequently as a result of prior radiation therapy. It often occurs years after the initial radiation exposure and can develop in a variety of locations, including the breast, chest wall, head, and neck. The incidence of RIAS is minimal, believed to be below 1% among radiation treatment patients. It is, nevertheless, a significant consequence of radiation treatment, emphasising the significance of long-term surveillance and monitoring for any late effects.¹³

Risk factors and latency period

Larger radiation doses, younger age at the time of radiation, and a longer duration following radiation exposure are all risk factors for developing (RIAS). The latency period, or the interval between radiation exposure and angiosarcoma growth, can range from a few years to many decades. The average delay period, however, is expected to be about 10-15 years. Healthcare practitioners must follow-up individuals who have had radiation therapy for breast cancer for any indications or symptoms of angiosarcoma to diagnose and treat the disease early.¹⁴

Clinical features and diagnosis

RIAS has different clinical characteristics. In the radiated breast region, patients frequently notice a fast-developing tumour or swelling. Bruising, discolouration, or ulceration of the skin may also occur. Clinical evaluation, imaging techniques (e.g., mammography, ultrasound), and histological (microscope) analysis of a tissue biopsy are used to make a diagnosis. The biopsy confirms the existence of angiosarcoma while ruling out other disorders. Specific immunohistochemical staining for markers such as CD31 and CD34 can help with the diagnosis. Early and precise diagnosis is critical for effective management and therapy. Close monitoring of individuals who have had breast radiation therapy is required to discover any suspicious symptoms or indications as soon as possible.¹⁵

Clinical evidence and outcomes

Studies and trials

Angiosarcoma after radiotherapy - a cohort study of 332,163 Finnish cancer patients assessed the risk of angiosarcoma after radiotherapy among all patients diagnosed in Finland between 1953 and 2003 with cancers of the breast, cervix uteri, corpus uteri, lung, ovary, prostate, or rectum, and lymphoma, as identified by the Finnish Cancer Registry. According to this research, 54% were women, and 76% were 55 or older at the time of their first primary cancer diagnosis. Patients who had radiation had an average age of 59 years old, whereas those who had not had radiotherapy had an average age of 66 years old. The study followed these patients for 1.79 million person-years, with a mean follow-up period of 5.4 years. Within this period, 19 cases of angiosarcoma were identified, indicating that the overall risk of angiosarcoma following radiotherapy is low.¹⁶

Managing side effects

Acute and late toxicities

Angiosarcoma caused by radiation treatment is an uncommon but dangerous consequence. Skin erythema (redness), oedema (swelling), and discomfort are symptoms of acute toxicity, whereas fibrosis (scarring), telangiectasia (spider veins), and ulceration are symptoms of chronic toxicity. These effects are mostly caused by endothelial cells and minor blood vessel injury.¹⁵

Minimising and managing side effects

Minimising side effects entails optimising the radiation treatment plan to limit the dosage to normal tissues and utilising sophisticated techniques such as intensity-modulated radiation therapy. Managing side effects entails managing symptoms with pain medicines, wound care, and supportive treatment. Close monitoring and surveillance are required to identify any possibility of recurrence or metastasis. Individualised interdisciplinary methods are advocated to accommodate the unique demands of each patient.¹⁷

Long term follow up

RIAS is a very uncommon side effect of radiation treatment. According to long-term follow-up studies, patients with this illness have a dismal prognosis, with median survival times ranging from months to a few years. Although surgical resection is the primary therapy, the high likelihood of regional recurrence and distant metastases offers considerable hurdles. More study is required to enhance the outcomes of these patients.¹³

Summary

Breast angiosarcoma is an uncommon malignant tumour that develops from blood vessels. It can happen on its own or as a side effect of radiation therapy for breast cancer. Radiation-induced angiosarcoma (RIAS) often develops several years following radiation therapy. When compared to primary angiosarcomas, these tumours have different clinical characteristics and poor prognosis. They tend to be more aggressive, more susceptible to localised recurrence and have a greater chance of distant metastasis. Treatment includes surgical resection, which is frequently accompanied by chemotherapy and radiation treatment. However, survival rates, in general, remain poor. More study is needed to comprehend the underlying processes and create more effective therapy techniques.