Metastatic Breast Cancer


Metastatic breast cancer, classified as Stage IV disease and also known as “advanced,” is cancer that has spread beyond the breast and surrounding lymph nodes into other areas of the body. Metastatic disease is usually diagnosed when breast cancer has recurred (returned), months or even years after treatment for earlier-stage disease. Breast cancer may also be diagnosed as advanced at the time of the original diagnosis, but this is less common.

While a diagnosis of advanced breast cancer can be overwhelming, research has led to many advances in treatment over the past several years. As a result, women with advanced disease are living longer.

Development of metastasis

Breast cancer metastasizes (spreads) when cancer cells break away from the breast tumor and enter the lymphatic system and bloodstream, where they can then travel to other parts of the body. The most common site of metastasis is bone, but other common sites include the lungs, liver and brain.

Metastasis is typically found either through routine follow-up tests or because of symptoms such as bone pain or shortness of breath. Even though the cancer is now in a different organ, the cells are still breast cancer cells, and so many of the same treatments used for earlier-stage breast cancer are used for metastatic disease, no matter where the metastatic lesions are located in the body. No current treatment cures metastatic breast cancer, however; treatment may only slow or prevent the progression of the disease.

Differences in breast cancers

You may have heard that no two breast cancers are alike. This is true. Advances in technology have enabled researchers to gain a better understanding of breast cancer, and they’ve found that many features of breast cancers differ. In addition, researchers have discovered tumor markers that help define and distinguish breast cancers. Tumor markers, also called biomarkers, are substances found in the body when cancer is present. Common biomarkers are proteins either produced by cancer cells themselves or by other cells in response to cancer, as well as genetic alterations linked to the development of some cancer.

Biomarkers help doctors personalize treatment by classifying breast cancer tumors according to a molecular subtype (Table 1). The distinction between these subtypes is important because results – such as response to therapy, the length of time without disease progression and survival – vary according to these subtypes.

Among the most well-known biomarkers in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and HER2 gene. Testing for ER, PR and HER2 is done on samples taken from the primary tumor or a metastatic lesion. The results of this testing are very important because they identify the breast cancers most likely to respond to specific treatments. The status of these biomarkers is so valuable in guiding treatment that two national cancer organizations – the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) – have recommended that these tests be done on all invasive breast cancers at the time of diagnosis. If you have metastatic disease that’s a recurrence of earlier breast cancer, your doctor can use the information from testing at the time of the original diagnosis. If testing was not done at that time or if test results were negative, testing should be done on a biopsy sample from a metastatic lesion. Similarly, testing should be done on a biopsy sample if metastasis is present at the time of first diagnosis. Testing should be done only at accredited laboratories, so talk to your doctor about the accuracy of the test results.


ER and PR

Many breast cancer cells produce receptors on their surface that can pick up the body’s hormones as they circulate through your body. These cancers are known as hormone receptor-positive, or HR+. Some breast cancers are especially sensitive to two such hormones, namely estrogen and progesterone. These two hormones can tell some breast cancer cells (those that carry the estrogen receptor and/or the progesterone receptor) to “turn on” the growth of breast cancer cells.

Breast cancers are classified according to the presence (ER+/PR+) or absence (ER-/PR-) of these receptors in the cells, and the amount of receptors (or expression) is also measured. ER and/or PR are expressed in as many as eight of every 10 breast cancers. A test may also show that your breast cancer is hormone receptor-negative (HR-), which means the cancer lacks these receptors and is not likely to be affected by treatments that block the hormones in your body.


When multiple copies of the human epidermal growth factor receptor-2 (HER2) gene are present (known as gene amplification), an excess production of the HER2 protein occurs. The HER2 protein sends signals that increase the growth of breast cancer cells, and high levels of HER2 are associated with fast-growing tumors. About one of every four breast cancers has a high level of the HER2 protein and/or gene and is therefore classified as HER2+ (positive). The remaining three of every four breast cancers lack a high level of HER2 and are classified as HER2- (negative).

Table 1. Molecular subtypes of breast cancer

Subtype Likely treatment response
ER+ and/or PR+, HER2- Typically responds to hormone (anti-estrogen) therapy.
ER+ and/or PR+, HER2+ Typically responds to hormone therapy and anti-HER2 drugs (targeted therapies).
ER-/PR-, HER2+ Typically does not respond to hormone therapy; typically will respond to anti-HER2 drugs.
ER-/PR-, HER2- (triple-negative) Typically treated with chemotherapy, as response to hormone therapy and anti-HER2 drugs is unlikely.

Take control

Women with metastatic breast cancer often feel isolated, but you are not alone. And the disease is not being ignored, as researchers are working every day to improve treatments. Uncertainty will likely be one of your biggest challenges. It’s very difficult for doctors to predict survival for women with metastatic breast cancer because every woman and every breast cancer is different. You can feel more in control by learning as much as you can about the specific characteristics of your breast cancer, your treatment options and ways you can help yourself, both physically and emotionally. Many women living with advanced breast cancer credit regular exercise, yoga, healthy nutrition, time with family and friends, support groups and spirituality with helping them during treatment for metastatic breast cancer.


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