Imaging Techniques For Breast Angiosarcoma Detection

Introduction 

Overview of breast angiosarcoma

Angiosarcoma is a type of cancer that originates from cells present within lymph vessels and blood vessels. In the case of breast angiosarcoma, this is a malignant form of cancer that can arise as a primary disease, or as a secondary disease, following radiotherapy treatment for primary breast cancer.¹ Specific studies, such as investigating the correlation between radiotherapy and soft tissue sarcoma, confirm that therapy-induced exposure to radiation increases the risk of developing breast angiosarcoma, although a small subset of patients who had previous breast cancer and no irradiation therapy have developed the condition.^2,3  To distinguish between both scenarios, the ex novo case is called primary breast angiosarcoma (PBA), while if the tumour arises after a previous form of breast cancer, as a secondary disease, it is defined as secondary breast angiosarcoma (SBA).¹ Several pathological and clinical differences are implied by this difference, as well as the fact that SBA appears generally later in life. While SBA originates from the skin, due to radiotherapy being delivered to the breast through the skin, PBA mainly originates from the underlying soft tissue, the parenchyma, and may or may not extend to the skin.

Importance of early detection and diagnosis

As for any other type of cancer, it is essential for the disease to be diagnosed as early as possible. Early successful detection of localised cancer, which refers to cancer present purely in the original site and has not yet started to spread- metastasize, in other areas of the body improves the patient's prognosis, which is the outcome after therapy.¹ Angiosarcoma of the breast is a very rare type of tumour, therefore, there is no unified methodology for its treatment. The more widespread use of breast-conservative surgery, which requires subsequent radiotherapy treatments, has increased the incidence of SBA. SBA occurs as the diagnostic signs of the tumour are often not nonspecific in imaging methods, which are utilised for direct tissue and organ visualisation. It is of fundamental importance to continue the study of imaging methods of breast angiosarcoma to define its diagnostic hallmarks, as this would aid future diagnosis, cancer surveillance, and therapies. 

Clinical presentation and diagnostic challenges

Symptoms and signs

The main clinical presentation of PBA is a palpable mass in the mammary gland of the breast, in the size range of centimetres, which can also cause ulcerations of the skin if the tumour extends to this area.¹ For this type of breast tumour, a diffuse sensation of breast fullness, swelling, or change in shape is not a common sign, although it is still possible that these symptoms appear.^1,2 The skin ulcerations are quite spread, therefore, it is easy to recognise them from small benign vascular skin cancers, but in SBA the clinical sign is often confused with post-radiotherapy skin damage, delaying the SBA diagnosis.¹ The skin changes associated with the disease are described in different ways, ranging from eczema-like rashes, diffuse swelling, hematoma-like swelling, to skin discoloration.³ 

Diagnostic challenges

A prominent challenge of breast angiosarcoma diagnosis, in particular in PBA, is the non-specific and polymorphic clinical presentations of the tumour. In the next section we will discuss how radiological techniques also face this challenge in diagnosis, but are essential to guide histological techniques, which are able to diagnose breast angiosarcoma with more accuracy.⁴ As this type of cancer does not have a unifiedly known imaging presentation, it should always be important to perform biopsies to precisely assess what condition we are facing. 

Imaging techniques

Mammography

A well established imaging technique for breast tissue is mammography, in which doctors will analyse the x-ray images of the patient. The aim of doing a mammography is to identify calcifications, which are calcium deposits, and masses, which are the areas in which the abnormal tissue is present. There are no clear clinical signs that determine whether a mammography results in breast angiosarcoma diagnosis, but there are some indications from patients with conclaimed breast angiosarcoma, through histological examinations, that can be useful for diagnosis in other patients.⁵ For example, no calcification is usually seen within the lesions, and usually the whole breast is involved. 

Unfortunately, mammography is not always able to detect the cancer also for the dense breast tissue present in young women.⁶However, the technique is useful to control for pathological changes after an initial diagnosis.⁵

Ultrasound

Ultrasound is not a main technique for breast cancer diagnosis, but it can be useful to see differences between fluid-filled spaces (cysts) and solid masses that could underlie cancerous tissue. Although not a first-line imaging technique for breast angiosarcoma detection, it has been reported that breast ultrasound, especially the technique which uses an extended field of view, has been useful to detect malignant cancer forms that were undiagnosed with other imaging methods.⁶

Magnetic Resonance Imaging (MRI)

Breast MRI is, like ultrasound, not the primary technique for cancer detection, as it can miss out some clinical signs or give ‘false positives’, which are suspected cancerous signs that are actually not present at a cellular level. It is, however, used to define the extent of the cancer and therefore it is essential to guide where biopsies should be done, and to distinguish this cancers from other malignant breast cancers, as the images will show more bleeding in patients with breast angiosarcoma in the affected areas.⁵

Other Imaging Modalities

Other imaging modalities are not of frequent use for diagnostic purposes, but can be important for surgical preparation: for example computed tomography (CT) can be used to detect metastasis of the tumour in further apart areas, while the purpose of positron emission tomography (PET) in combination with CT has not been evaluated yet, and PET in combination with MRI in not under current investigation.¹ It would be therefore important in the future to study these alternative techniques to assess their diagnostic use, and understand whether these could improve diagnosis accuracy and rapidity.

Imaging-guided biopsy and histopathology

To assess the type of tumour, the pre-surgical stages and to find the best treatment for breast located cancers, biopsies of the tissue are taken to analyse the disease at a cellular level and reach for a diagnosis: through biopsies the pathological cellular changes in a disease can be evaluated under the microscope.

Two techniques for having tissue biopsy taken are core needle biopsy and fine-needle biopsy. Fine-needle biopsy can be both performed as tissue sampling or as vacuum aspiration of the tissue of interest, of which then a part is cut for external examination.⁸ Core needle biopsy is a more recent technique that is preferable to fine needle: in fact, although fine needle is inexpensive, does not require anaesthesia and results are delivered more quickly, it is less efficient for diagnostic purposes than core needle technique.⁷ Core needle technique uses larger needles and is more efficient for tumour detection, and provides more information about the nature of the pathological cell changes, therefore it is a better choice for assessing the presence of breast angiosarcoma.In addition to these, a third method, vacuum-assisted biopsy is extremely helpful in taking larger samples, and compared to core-needle-biopsy, has the benefit of permitting the sampling of multiple tissues, without the removal and reinsertion of the needle.⁸

Since imaging methods have been implemented as a preliminary guide for biopsies, the hospital-stay period for patients is reduced, while the efficacy and precision of the biopsy has increased.Preliminary imaging methods are essential to identify impalpable masses, and to detect the lesion location with more precision, improving the diagnosis accuracy.

Treatment and management

Treatment for the disease is not completely standardised, as we are facing a rare form of breast cancer, however it appears that the main complications are linked with SBA, due to the fact that the pathology is usually clinically more advanced.⁹ In fact, if this factor is taken into consideration, it appears that the PBA and SBA have similar prognosis rates, as they share a similar underlying tumour biology.³

The main treatment option is mastectomy, which is a surgical procedure that involves removal of the breast, although, in early stages, breast cancer can also be treated through conservative breast surgery, in which only the cancer lumps are removed and the breast is not removed. The surgery type selection should also happen depending on whether we are facing PBA or SBA, as the expected prognosis is different. Surgery for breast angiosarcoma is almost always the main practice used, and the procedure will depend on the stage and size of the tumour itself.¹

Other than surgery, some adjuvant therapies might be prescribed but, as breast angiosarcoma is such a rare condition, their efficacy is not well assessed. Chemotherapy can be prescribed, although some of the substances used in chemotherapy seem to be toxic at a cellular level in breast angiosarcoma. More controversial is the use of radiotherapy, which seems to be the cause of SBA in the first place: it could be that this therapy worsen the condition, although it has been reported that, after surgery, radiotherapy has been helpful on a subgroup of SBA patients. 

As surgery is needed for treating the condition, it is important to check the state of the patient after the intervention for the surveillance of the tumour and its metastatic state, which is its spread from the site of origin. Cellular changes can be assessed through mammography, while the spread and the size of the tumour can be monitored with imaging techniques, for example CT is often used to assess the metastatic state of the tumour. Mammography is also useful to assess the appearance of SBA after radiotherapy for breast cancer: with this technique the skin thickening can be studied, and in case of normal healing from primary breast cancer, the skin thickening is expected to be reduced after approximately two years. 

Prognosis and outcomes

For PBA, mastectomy seems to have lower survival rates than breast conservative surgeries. This result might be due to the fact that mastectomy is performed in more severe clinical cases: the actual main correlating factors for survival rate are in fact age and tumour stage.³

Both PBA and SBA have in common that adjuvant radiation therapies are correlated with a lower survival rate.

A review by Naka et al., (1996) summarises the findings on 55 patients with different forms of angiosarcoma, and concludes that, statistically, the prognosis of an angiosarcoma depends on its mitotic count, which is a measure of tumour growth, while the survival depends on factors relating to the individual, such as age and tumour size, but also treatment strategy, including surgery success and prescription of the relevant adjuvant therapies, like chemotherapy.¹⁰  As far as chemotherapy is concerned in the particular case of breast angiosarcoma, the efficacy is less clear, and seems to have improved survival rates mostly in SBA.¹ Since the time the review was published, some more consistent findings regarding the treatment of angiosarcomas have been possible through patient-driven initiatives: one is the Angiosarcoma Project, which collects information, data and genetic analysis on the disease by affected patients.

Summary

Breast angiosarcoma is a rare type of cancer that involves the lymph and blood vessels in the breast soft tissue. It can originate directly from these in the case of Primary Breast Angiosarcoma, or be a consequence of previous radiotherapy, therefore originating from the skin tissue, and this disease form is called Secondary Breast Angiosarcoma. The condition is clinically assessed primarily through analysis of tissue samples during biopsies. However, to improve the efficacy of biopsies, imaging techniques are fundamental as they accurately identify the location of the cancer and its spread. These techniques, consisting of MRI scans, ultrasound and mammography, can better assess the clinical picture of the patient and help plan surgeries. In the case of mammography, this technique is also useful to detect pathological changes after the initial diagnosis. Unfortunately, our knowledge on clinical signs of breast angiosarcoma seen through imaging methods is not complete enough to allow straight-forward diagnosis: it is therefore important to keep researching clinical imaging findings to exploit these techniques to their full potential, but also to undertake other testing methods to reach an accurate and fast diagnosis of breast angiosarcoma, both in its primary or secondary forms.