Breast Angiosarcoma

Breast angiosarcoma is a very rare and aggressive cancer that starts in the cells lining blood or lymph vessels in the breast. While it accounts for less than 1% of all breast cancers, people who have received radiation therapy for breast cancer face a higher risk of developing this disease years after treatment.

Table of contents

• What is breast angiosarcoma?
• Types of breast angiosarcoma
• Symptoms and warning signs
• How is breast angiosarcoma diagnosed?
• Treatment approaches
• Outlook and prognosis

What is breast angiosarcoma?

Breast angiosarcoma is a very rare type of cancer that develops in the blood vessels or lymph vessels in the breast. Angiosarcoma refers to a cancer that begins in the cells lining blood and lymph vessels, and it represents about 1% of all soft tissue breast tumors^[1]. This cancer is so rare that for every 1 million people in the United States, only one will be diagnosed with an angiosarcoma each year^[1].

Because so few people are diagnosed with this disease, researchers are still trying to determine how best to stop it from spreading or coming back^[1]. The cancer can behave aggressively, growing rapidly and spreading to other parts of the body^[2].

Angiosarcoma accounts for less than 0.04% of all malignant tumors and typically arises in the tissue of the breast with occasional skin involvement^[2]. It represents only about 0.1% to 0.2% of all cases of breast cancer and can affect both women and men^[7].

Types of breast angiosarcoma

There are two main types of breast angiosarcoma, and they differ significantly in their causes, the age of people affected, and how they present.

Primary breast angiosarcoma

Primary breast angiosarcoma occurs in people who have never had breast cancer before. This type develops without any known factors or previous radiation therapy^[1]. It most commonly develops when people are in their 30s and 40s^[1][2]. The causes and risk factors of primary breast angiosarcoma are not as well understood as the secondary form, mainly because of how rare this cancer is^[1].

Primary angiosarcoma typically presents with poorly defined masses and usually arises in the tissue of the breast^[2]. People with primary angiosarcoma often present with a mass in the breast^[1].

Secondary breast angiosarcoma

Secondary breast angiosarcoma, also called treatment-related or radiation-induced angiosarcoma, occurs in people who have been previously treated for breast cancer^[1]. This form is most commonly associated with previous radiation therapy^[2]. It presents in older women, with a median age of 67 to 71 years, and typically develops 7 to 10 years after radiation therapy for breast cancer^[1][2].

If you have received radiation therapy for breast cancer, your risk of developing breast angiosarcoma may be higher. A report from 2019 estimated that 1 in 1,000 people who had radiation for breast cancer went on to develop angiosarcoma in the breast or chest wall^[1].

In addition to radiation therapy, some research suggests that removal of lymph nodes and chronic lymphedema (swelling) in the breast or arm may increase the risk of breast angiosarcoma^[1]. The median latency period from radiation therapy to the development of angiosarcoma ranges from 5 to 10 years^[2].

Although a direct cause-and-effect relationship between radiation exposure and angiosarcoma has not been definitively established, multiple case reports support the increased risk following radiation therapy^[2]. It has been proposed that at radiation doses greater than 50 Gy, cell death occurs, while at doses less than 50 Gy, DNA damage and instability result. Sarcomas frequently occur at the edge of radiation fields where doses may be uneven^[2].

Symptoms and warning signs

The symptoms of breast angiosarcoma vary depending on whether it is primary or secondary, though both types can share some common features.

Symptoms of primary breast angiosarcoma

Symptoms of primary breast angiosarcoma can include^[1]:

• A thickened area of skin on the breast
• A lump in the breast
• Discolored rash or bruised appearance on the skin of the breast or arm

Symptoms of secondary breast angiosarcoma

Symptoms of secondary breast angiosarcoma can include^[1]:

• Swelling in the breast or arm
• A lump in the breast
• Discolored rash or bruised appearance on the skin of the breast or arm

While many people with primary angiosarcoma often present with a mass in the breast, secondary angiosarcoma can often appear as a skin tag, pimple, or purple or blue-hued lesion on the breast^[1]. A breast surgical oncologist notes that people sometimes initially go to a dermatologist because they think it is a skin problem, which can lead to delays in diagnosis because healthcare providers are not necessarily looking for angiosarcoma^[1].

The most common symptom is a noticeable lump or mass under the skin or in deeper tissues that may be painful. Other symptoms may include skin changes such as reddish or bluish discoloration, swelling in the affected area, pain, bleeding, and fatigue^[7].

While the risk of angiosarcoma is low, it is important for people who are receiving radiation for cancer to be aware of it. This way they know to reach out to their doctor immediately if they notice symptoms of the disease, which include a rash or bruise on the breast that does not go away^[1].

How is breast angiosarcoma diagnosed?

If you identify a breast lump, pimple, or a bruise on your breast that is not going away, you should contact your doctor right away^[1]. They will likely perform a series of tests to determine what is causing your symptoms.

The diagnostic process typically includes a physical exam, imaging, and a biopsy^[1]. However, angiosarcoma is often diagnosed at a more advanced stage due to its rarity and similar symptoms with other breast cancers, which stresses the importance of early detection and screenings^[7].

Final diagnosis requires pathological and immunohistochemical confirmation^[11]. A biopsy involves taking a small sample of tissue from the affected area to examine under a microscope for cancer cells.

Treatment approaches

The treatment of breast angiosarcoma typically involves multiple approaches because of the aggressive nature of this cancer.

Surgery

For stage I angiosarcomas, surgery to obtain adequate margins is recommended^[12]. Surgery is the primary treatment and may involve lumpectomy (removal of the tumor and some surrounding tissue) or mastectomy (removal of the entire breast). Because angiosarcoma can spread within the breast tissue, achieving clear margins—meaning no cancer cells at the edges of the removed tissue—is crucial.

For stage II and stage III disease that can be removed with acceptable functional outcomes, preoperative radiation therapy is also recommended^[12]. For stage III disease, other recommendations include preoperative combination of chemotherapy and radiation, or chemotherapy alone, and postoperative combination of chemotherapy and radiation^[12].

Chemotherapy

The conventional treatment options include surgery, radiation therapy, and chemotherapy^[11]. Angiosarcoma is highly sensitive to certain chemotherapy drugs called taxanes, and paclitaxel has proved well tolerated and active even in previously treated patients with locally advanced or widespread angiosarcoma^[12]. Paclitaxel is used as single-agent therapy and is administered weekly^[12].

Other chemotherapy regimens that are preferred for treatment of angiosarcoma include^[12]:

• Paclitaxel
• Drugs containing anthracyclines (such as doxorubicin and epirubicin)
• Gemcitabine-based regimens (such as gemcitabine combined with docetaxel, vinorelbine, or dacarbazine)

Neoadjuvant chemotherapy, which is chemotherapy given before surgery, can be considered in patients with large localized angiosarcomas where achieving negative margins may be challenging^[12]. However, response to preoperative chemotherapy is only 40 to 50% with the most active regimens, and toxicity is significant^[12].

Radiation therapy

For secondary angiosarcoma that develops after previous radiation therapy, additional radiation to the same area is typically not recommended because of the risk of further complications.

Targeted therapy and immunotherapy

Targeted medicines and immunotherapy have been studied as promising treatments for angiosarcoma^[11]. Some patients with angiosarcoma with specific genetic changes in vascular signaling genes may respond well to targeted drugs like pazopanib^[12].

Outlook and prognosis

Angiosarcoma can be aggressive, and the prognosis depends on several factors, including the stage of the cancer, the size and location of the tumor, whether it is primary or secondary, and the response to treatment^[7].

Angiosarcoma tends to have a poorer prognosis compared to more common types of breast cancer. Cancer tumors can grow quickly and may invade surrounding tissues, making them more difficult to treat^[7]. Angiosarcoma also has a high risk of recurrence, even after aggressive treatment with surgery, radiation therapy, and chemotherapy^[7].

The reported rates of advanced or widespread disease at the time of diagnosis vary from 16% to 44%, and overall survival ranges from 6 to 16 months for advanced disease^[11]. Angiosarcoma is a highly malignant tumor and represents 1% to 2% of all soft tissue sarcomas in humans^[11].

Because so few people are diagnosed with this disease, researchers are still working to determine the best treatments to stop it from spreading or coming back^[1]. However, with appropriate treatment and close monitoring, some patients can achieve good outcomes and remain disease-free for extended periods.