An Overview of Metaplastic Breast Cancer

Metaplastic breast cancer (metaplastic carcinoma of the breast) is a very uncommon type of breast cancer. It is a form of invasive ductal cancer, meaning that it forms in the milk ducts and then moves into other tissues of the breast. It can be aggressive and fast-growing, and relatively little is known about metaplastic breast cancer's causes or long-term prognosis.

Metaplastic breast cancer differs from other types of breast cancer in that it often contains other types of tissue not normally found in the breast, including squamous cells (skin) or osseous cells (bone). "Metaplastic" comes from the Greek phrase for "changed in form," which is why it describes cells that appear to have morphed into those of another part of the body.

This article discusses the symptoms and diagnosis of metaplastic breast cancer. It also covers treatment options and how to cope with a diagnosis.

Metaplastic Breast Cancer Symptoms

Some people with metaplastic breast cancer have no symptoms at all and are identified through routine screening. For others, the symptoms are essentially the same as for other types of breast cancer.

Symptoms may include:

• Lumps or thickening in the breast that were not there before
• Tenderness, discharge, or change in appearance of the nipple
• Changes in the appearance of breast skin (e.g., redness, scaling, puckering or dimpling)
• Irritation of the breast, including redness, swelling, and rash
• Unexplained pain in the breast, especially with any of the above symptoms

Diagnosing Metaplastic Breast Cancer

Tests to diagnose breast cancer are similar no matter what type of cancer is present.

Imaging

Imaging tests come first and may include:

• Diagnostic mammography: This is much like your routine screening mammogram, except that diagnosing cancer (rather than just checking for it) requires more images to be taken and examined.
• Ultrasound: This uses high-frequency sound waves to produce images of breast tissue. These images help doctors determine whether a lump in the breast is a fluid-filled cyst or a solid tumor.
• Magnetic resonance imaging (MRI): This uses magnetic fields to produce images of the inside of the body.
• Computed tomography (CT or CAT) scan: This creates multiple "slice by slice" pictures of the inside of the body, and then combines them into a detailed cross-section picture that can show the presence of tumors.
• Positron-emission tomography (PET) scan: After an injection of radioactive sugar molecules, a PET scan is taken to see which areas of the body are absorbing the sugar most quickly. Because cancer cells thrive on sugar, they "light up" on a PET scan.
• PET-CT scan: This combines the technology of PET and CT scans, allowing doctors to observe which cells may be cancerous and determine more precisely where they are in the body.

On mammography, metaplastic breast cancer can appear very similar to both ductal carcinoma and benign masses, which can make the diagnosis more challenging.

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Breast Biopsy

Any of the imaging tests above may be helpful in learning more about a tumor, but a breast biopsy is needed to determine the exact type of breast cancer and to learn about characteristics of the tumor, such as tumor grade (the aggressiveness of the tumor). No two breast cancers are alike—even tumors that are diagnosed as metaplastic breast cancer.

To specifically diagnose metaplastic breast cancer, the breast tissue must be biopsied, meaning that a bit of tissue is removed from the breast (surgically or with a special needle) and examined under a microscope. If there is any suspicion of a malignancy on an imaging test, a biopsy will be done to confirm whether the area is benign or malignant.

Receptor Testing

As with other types of breast cancer, special tests are performed on biopsy samples to determine receptor status.

Some tumors are estrogen-receptor (and/or progesterone-receptor) positive, meaning that estrogen binds to the receptors causing the growth of the tumors. Treatments that either block the receptor or reduce the amount of estrogen in the body can limit the growth of the tumor.

HER2 testing can determine if the tumor is HER2-positive, meaning that the cells have an increased number of HER2 receptors on the surface. Growth factors bind to these receptors causing the growth of the cancer, and medications that block the HER2 receptor can thus interfere with growth. Overall, roughly 25% of breast cancers are HER2-positive, but it's uncertain exactly how common HER2 positivity is in metaplastic breast cancer.

Treating Metaplastic Breast Cancer

Metaplastic breast cancer is less likely to be estrogen-receptor-positive or HER2-positive, which limits treatment options. Tumors tend to respond poorly to chemotherapy, though radiation can be effective. New hope is vested in targeted therapies that may improve survival and give rise to better treatments in the near future.

As with all cancer, treatment of metaplastic cancer is at first guided by:

• The size and location of the tumor
• Whether the cancer has spread (this includes regional spread to lymph nodes, as well as distant spread to areas such as the bones, liver, lungs, and brain)
• Overall health
• Age at diagnosis
• Receptor sensitivity

Surgery

A lumpectomy or mastectomy is the most definitive treatment. Since metaplastic breast cancers tend to be larger than other types of breast cancer at diagnosis, mastectomy may be recommended.

Radiation Therapy

One of the larger studies to date, a 2017 study looking at treatment options, found that adjuvant radiation therapy was as important as surgery and chemotherapy in preventing local and regional recurrences in metaplastic breast cancer.

Hormone Therapy

For tumors that are estrogen-receptor and/or progesterone-receptor-positive, hormonal therapy is often used. However, the incidence of hormone receptor-positive disease is lower with metaplastic breast cancer, and the majority of these cancers are hormone-receptor negative.

For premenopausal women, the medication tamoxifen is most often used. This drug works by binding to estrogen receptors on breast cancer cells so that the hormone can't.

For women who are postmenopausal (or those who are premenopausal and have received ovarian suppression therapy), treatment with an aromatase inhibitor is usually used. Aromatase inhibitors work by blocking the conversion of male hormones (androgens) to estrogen, thus reducing a growth factor for some breast cancers.

HER2-Targeted Therapies

Until 1998 and the approval of the drug Herceptin (trastuzumab), HER2-positive tumors held a poorer prognosis. There are now additional HER2 targeted therapies available that work by binding to the HER2 protein on cancer cells so that growth factors cannot—thus stopping cancer growth. These medications are not, however, effective for tumors that are HER2-negative.

Chemotherapy

Many of these cancers are at a higher stage than average for breast cancer at diagnosis, so chemotherapy is often recommended. That said, chemotherapy does not appear to be as effective for metaplastic breast cancer.

mTOR Inhibitors

Treatment options for metaplastic cancers that are estrogen-receptor and HER2-negative (triple-negative) are more limited since chemotherapy is not particularly effective, but research offers promise.

A 2018 study looked at the response of these tumors to mTOR inhibition (a type of targeted therapy) with the drugs Afinitor (everolimus) or Torisel (temsirolimus). It was found that people with metaplastic triple-negative breast cancers had better outcomes with this treatment than those who had non-metaplastic triple-negative tumors.

However, the inclusion of mTOR inhibitors is not standard treatment for metaplastic breast cancer. At the present time, this would only be done in the context of a clinical trial.

Clinical Trials

There are many clinical trials in progress for breast cancer looking for more effective treatments or ones that have fewer side effects.

While there are many myths about clinical trials, it's important to keep in mind that every treatment currently available was once evaluated in a clinical trial, and sometimes clinical trials offer the best option for treating breast cancer. For example, the use of a P13K inhibitor (buparlisib) for metaplastic breast cancer was found to have a long-lasting response in an isolated 2018 report.

Coping With Metaplastic Breast Cancer

Having such a rare form of breast cancer may leave you feeling isolated and confused. While it's unlikely that you have a support group for metaplastic breast cancer in your community, given how uncommon it is, you can connect with others facing this diagnosis via social media. Many people find it helpful to participate in general breast cancer support groups and support communities as well.

It's also important to become educated about your cancer and research that is being done, and to be your own advocate (or have a friend who can advocate for or with you) in your cancer care.

After your diagnosis, you may find it disconcerting that less is known about this type of cancer. It's sometimes helpful to seek care at one of the larger cancer centers (such as one of the National Cancer Institute-designated cancer centers), which are more likely to have surgeons and oncologists who have experience with metaplastic cases.

Summary

Metaplastic breast cancer is a rare form of invasive ductal cancer. The fast-growing cancer starts in the milk ducts and moves into other areas of the breast. Symptoms may include a lump or change in the breast or nipple, including thickening, tenderness, discharge, or irritation. It can be diagnosed through imaging such as mammography or ultrasound and a breast biopsy.

Treatment depends on the size and location of the cancer but may include surgery, radiation, hormone therapy, HER2-targeted therapies, chemotherapy, or mTOR inhibitors. Clinical trials may also provide options for treatments.