Advanced (Metastatic) Breast Cancer

The term, metastatic, describes a cancer that has spread to distant organs from the original tumor site. Metastatic breast cancer is the most advanced stage (stage IV) of breast cancer. Cancer cells have spread past the breast and axillary (underarm) lymph nodes to other areas of the body where they continue to grow and multiply. Breast cancer has the potential to spread to almost any region of the body. The most common region breast cancer spreads to is the bone, followed by the lung and liver. Treatment of metastatic breast cancer generally focuses on relieving symptoms and extending a woman’s lifetime.

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Diagnosis

Breast cancer often begins in the breast ducts as ductal carcinoma in situ (DCIS). Once out of the breast, cancer often spreads first to the axillary (underarm) lymph nodes. One or more of the lymph nodes are usually removed during breast surgery to determine whether the nodes are involved. (See the axillary node dissection and sentinel node biopsy sections for more information on how lymph nodes are removed). In some cases, breast cancer may spread to other regions of the body without involving the axillary lymph nodes. If the cancerous tumor is located in the medial portion of the breast (near the nipple), it may spread to the internal mammary nodes which are located between the ribs and beneath the sternum. In some cases, cancer may spread through the bloodstream without being detected in the lymphatic system.

In 10% of breast cancer diagnoses, the cancer has already spread to distant organs in the body. A primary diagnosis of Stage IV breast cancer may indicate a rapid progression of the disease or that the cancer was present but not detected in the breast for some time. To help detect breast cancer in its earlier stages when it is most curable, women should follow the guidelines for early detection established by the American Cancer Society which include monthly breast self-examinations, annual clinical breast exams, and annual mammography (the latter beginning at age 40).

Metastatic breast cancer may also occur from a recurrence (return) of breast cancer after initial treatment. There are three types of breast cancer recurrences: local, regional, and distant. Local and regional recurrences are usually less serious than distant recurrences and may be detected by mammogram or seen as abnormalities with breast imaging exams (such as ultrasound or T-scan).  Once a local or regional recurrence is detected, physicians will order a variety of other tests to determine whether the cancer has metastasized (spread) to distant organs. These tests include:

Blood tests (also called tumor marker tests) measure non-specific markers found in the blood that can be followed over time. Two such markers for breast cancer are CEA (carcinoembryonic antigen) and CA 15-3. These markers tend to be elevated in women with metastatic breast cancer. However, because the tests are not very sensitive, they are not usually very useful for patients with early-stage breast cancers.

CEA, or carcinoembryonic antigen, is a "marker" for breast or other cancer recurrence. It is a special protein that is actually produced in embryonic cells and regenerating cells, as well as cancer cells. This protein is found on the surface of cells and can be measured in blood tests, as cells shed these proteins. In the past, these markers have been used to monitor a patient after treatment for cancer; a rise in the level would indicate the need to search more fully for a recurrence of cancer. For example, it may trigger a patient's doctor to order a battery of tests, such as chest x-rays, CT scans and so on, to look for recurrent or metastatic tumor in organs such as the lung or liver.

However, the CEA level can also be elevated in a number of benign (non-cancerous) conditions. Some of these include stomach ulcers, colon polyps, cigarette smoking, among other causes. If an oncologist has not found any reason to suspect cancer recurrence, then patients are usually correct to follow his or her advice. Some oncologists do not use these markers to follow patients anymore as it sometimes creates unnecessary anxiety.

CA 15-3 is another serum cancer antigen that is used in the management of some patients with breast cancer. It is most effective at monitoring metastatic breast cancer, but has not had high success at detecting early stage breast cancers. While CA 15-3 is not typically used alone in evaluating metastatic breast cancer patients, it can provide useful additional information about whether a patient is responding to treatment.

If the cancer has not spread to other organs, treatment of local or regional recurrences often depends on how the initial treatment was performed. If lumpectomy was performed, recurrent breast cancer will usually be treated with mastectomy. If the cancer has spread to other areas of the body, the situation is more serious.

Symptoms of metastatic breast cancer may include:

  • Bone pain (possible indication of bone metastases)
  • Shortness of breath (possible indication of lung metastases)
  • Lack of appetite (possible indication of liver metastases)
  • Weight loss (possible indication of liver metastases)
  • Neurological pain or weakness, headaches (possible indications of neurological metastases)

These symptoms are sometimes but not always associated with metastatic breast cancer, and having one or more of these symptoms does not necessarily mean a woman has metastatic breast cancer. Most women whose breast cancer has metastasized do not show symptoms until the disease is extensive.

Where Can Breast Cancer Spread?

Breast cancer can spread to almost any area of the body. The most common regions that breast cancer may spread to in order of frequency are:

  • Bone
  • Lung
  • Liver

Bone: Approximately 25% of breast cancers spread first to the bone. The bones of the spine, ribs, pelvis, skull, and long bones of the arms and legs are most often affected. There are two types of bone metastases: osteolytic and osteoblastic. With osteolytic metastases, the cancer eats away at the bone, forming holes. This most often occurs in the legs, hip, or pelvis. Osteoblastic metastases actually increase bone mineral density but also cause bones to fracture easily. Both types of bone metastases cause pain.

Researchers are investigating whether a class of drugs called bisphosphonates may be helpful in treating effects of bone metastases. Bone metastases can cause pain, decreased activity, and potentially severe problems such as fractures. Other complications that can arise from bone metastases include the surgical treatment for fractures, hypercalcemia (abnormally high levels of calcium), and spinal cord compression (vertebral damage due to pressure on the spinal cord).

Currently, Aredia is the only FDA-approved bisphosphonate to treat breast cancer patients with bone metastases. Aredia is administered intravenously (through a vein) along with other cancer treatments, such as chemotherapy. Clinical studies have shown that breast cancer patients with bone metastases who are given Aredia tend to experience a delay in or reduction of bone pain, fractures, and other bone complications compared to patients who do not receive Aredia. Possible side effects of Aredia include fever, fatigue, nausea and vomiting, initial bone pain, lack of appetite, and anemia (decrease in red blood cells).

Other bisphosphonates have also shown promise in alleviating symptoms of bone metastases. In a recent study, an experimental bisphosphonate called ibandronate stopped the progression of bone metastases in mice and halted the formation of new metastases. Other bisphosphonates under investigation for treating bone metastases include:

  • Didronel (generic name, etidronate)
  • Bonefos, Clostoban, Loron, Ostac (generic name, clodronate)
  • Skelid (generic name, tiludronate)
  • Fosamax (generic name, alendronate)
  • Zometa (generic name, zoledronate)

At this time, most physicians do not see sufficient evidence to recommend bisphosphonates for breast cancer patients who do not already have bone metastases.

Lung:Between 60% and 70% of women who die from breast cancer have eventually had it spread to their lungs. In 21% of cases, the lung is the only site of metastatis (spread). The most common signs of lung metastases are: shortness of breath and dry cough. In some cases, women will not experience any symptoms; cancer will only be detected by chest X-ray or CT scan.  In rare cases, part of the lung may be surgically removed if the cancer is confined to one area. However, in most cases, the cancer has spread itself throughout the lung and is more effectively treated by chemotherapy or other anti-cancer drugs.

Liver:The liver is the third most common site for breast cancer to spread to after bone and lung. Two-thirds of women with metastatic breast cancer eventually have it spread to the liver. Symptoms of liver metastases are subtle at first but become increasing intense over time. Weight loss, loss of appetite, fever, and gastrointestinal disorders may indicate liver metastases. Liver blood tests may first detect cancer in the liver. However, a liver biopsy is necessary to distinguish between cancerous tumors and other abnormalities.

Breast cancer may also spread to other regions of the body. Though these sites are less common, breast cancer may infect the bone marrow, brain, ovaries, spinal cord, eye, and other areas.

Treatment

The majority of treatments for metastatic breast cancer focus on alleviating symptoms. Therapies will differ depending on the patient’s history of treatment and how well she responds to specific therapies.

Surgery is rarely an option because the cancer is not usually confined to one specific spot on the organ. Radiation therapy may be used, depending on the extent to which the cancer has spread throughout an organ. The purpose of radiation therapy in cases of metastatic breast cancer is usually to shrink the cancer and provide pain relief. If cancer is only on one or more spots of the bone, for example, radiation may be done.

Systemic therapies such as chemotherapy or other drug therapies are usually given to advanced breast cancer patients because they affect the entire body (as opposed to localized treatments that only affect one area). Chemotherapy is treatment with anti-cancer drugs. Most courses are three to six months long and may be given daily, weekly, or monthly, depending on the body’s response to the drugs. Chemotherapy sessions are not usually continuous; they include rest cycles because chemotherapy targets both healthy and cancerous cells.

Researchers are investigating whether aggressive, high-dose chemotherapy is effective in patients with advanced breast cancer. Some recent research shows that high-dose chemotherapy may improve a patient's outcome. However, other studies have shown no advantage.

In addition, a new blood test, called CellSearch CTC, shows promise in helping to manage treatment of metastatic breast cancer. The test measures the number of tumor cells circulating in a sample of blood and can immediately inform physicians if a patient's treatment is working or needs modification. Research has shown that if a patient typically has more than five CTCs in a blood sample, survival may be shorter compared to patients with no CTCs. The CTC test can help physicians monitor whether a patient's treatment by determining whether the number of cancer cells is decreasing. This information can help determine whether changes are needed in a patient's treatment. While the test is used independently-typically before each chemotherapy treatment cycle-health experts do not recommend that it replace existing tests to monitor disease progression, such as the CAT scan or PET scan. Instead, it can be a useful supplement to those tests, which are often administrated every 12 to 24 weeks. Click here to learn more about the CTC test.

In addition to chemotherapy, patients with advanced breast cancer may be treated with several drugs:

Drugs called bisphosphonates may also be used to treat bone metastases (see above section for more information).

Coping With Metastatic Breast Cancer

In a survey sponsored by the National Alliance of Breast Cancer Organizations (NABCO), the majority of the 200 women with metastatic breast cancer surveyed said the public perceives them as being "near death—with little or no time to live." However, nearly 20% of women with metastatic breast cancer live five years or longer. It is important for patients and physicians to be realistic about the outcome of advanced breast cancer, but at the same time, the survival rate  (16%) is based on statistics. Each woman is unique and her situation will also be unique.

There are several resources available to help women cope with metastatic breast cancer. Here are a few:

  • The National Cancer Institute’s booklet, "Advanced Breast Cancer: Living Each Day." This booklet provides advice on how to deal with the physical and emotional burdens of metastatic breast cancer. A copy of the booklet is available online at http://www.cancer.gov/cancertopics/advancedcancer. Call 1.800.4.CANCER (1.800.422.6237) for information on how to receive a copy of the NCI booklet.
  • Contact the American Cancer Society for published information and local support groups at 1.800.ACS.2345. (1.800.227.2345).
  • Advanced Breast Cancer: A Guide to Living With Metastatic Disease (1998) by Musa Mayer offers advice on how to cope with advanced breast cancer. Mayer weaves excerpts from interviews she has conducted with women who have metastatic breast cancer throughout the book.
  • The Y-ME National Breast Cancer Organization has a 24-hour hot-line women may call for services and support: 1.800.211.2141.
  • The Susan G. Komen Foundation provides a 24-hour helpline that is answered by trained, caring volunteers whose lives have been personally touched by breast cancer. Helpline volunteers give timely and accurate information to callers with breast health and breast cancer concerns: 1.800.I’M AWARE (1.800.462.9273).
  • Talk to a counselor, family member, friend, breast cancer survivor, therapist, or clergyman or woman.

Additional Resources and References

Updated: October 30, 2007

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