Breast Cancer Metastasis

Breast cancer can spread, or metastasize, to almost any region of the body. In 10% of new breast cancer diagnoses, the cancer has already metastasized.

Breast cancer that has spread to other parts of the body is still referred to as breast cancer, even though it may be in the lungs or liver. For instance, a breast cancer that has spread to the lungs is termed "breast cancer with lung metastasis", not lung cancer. This is because the cells that the cancer first arose in were breast cells, and those cells have different characteristics than lung cells. Those characteristics play an important part in how the cancer behaves and in its treatment.

Lymph Node Involvement

Very often the cancer cells travel first to the nearby axillary (underarm) lymph nodes, so the lymph nodes are biopsied and samples of the tissue are examined under a microscope to see if cancer is present. If the tumor is located near the nipple, it may spread to the internal mammary nodes, located between the ribs and beneath the breastbone.

There seems to be a relationship between the number of lymph nodes involved in the cancer and how aggressive the cancer is, so finding out lymph node involvement by biopsying lymph node tissue helps in planning treatment.

Lymph node involvement is categorized in three ways:

• Minimal involvement (only a few cancer cells are found).
• Significant involvement (a particular node or group of nodes is involved).
• Extracapsular extension (a tumor has taken over a whole node and penetrated into the surrounding fat tissue).

Lymph Node Biopsy

When breast cancer spreads beyond the primary tumor site, it usually spreads first to the sentinel lymph node or nodes, the first lymph nodes to receive drainage from a cancer-containing area of the breast. From there, breast cancer generally spreads to the axillary lymph nodes under the arm. So an important part of the breast cancer staging process is to determine whether the cancer has spread from the primary tumor to the sentinel lymph node, and from there into the axillary lymph nodes.

Lymph Node Biopsy

Axillary Lymph Node Dissection

Most lymph node biopsies are axillary lymph node dissections, a traditional procedure that is still considered the gold standard. In it, most of the lymph node tissue from under the arm (10-30 lymph nodes) is removed and sent to a lab to find out if cancer is present. A drain is implanted under the patient's arm and left in place for 2-3 weeks to drain off lymph fluid. About 10-20% of patients who have an axillary lymph node dissection experience long-term problems such as lymphedema (arm swelling) and pain in the area of the dissection.

Sentinel Lymph Node Biopsy

Sentinel lymph node biopsy is a new procedure that seeks to spare the patient the discomfort and possibly chronic side effects of the axillary lymph node dissection. Because breast lymph fluid drains first to the sentinel lymph node, if that node proves to be free of cancer, then the chances are excellent that cancer hasn't spread beyond the sentinel node to the axillary nodes.

The sentinel node must first be identified before it can be biopsied. This is done by injecting substances into the cancerous area of the breast. One is a weakly radioactive tracer (technetium 99); the other is a blue dye (isosulfan blue) that stains the lymph tissue a bright blue. Most surgeons use a combination of the two dyes.

After the tracer and dye have been injected, the surgeon waits for them to travel from the tumor area to the sentinel lymph node, as cancer cells would. The waiting period may be from 45 minutes to 8 hours. When the patient has been brought into the operating room, the surgeon scans the sentinel node area with a handheld gamma-ray counter (also known as a Geiger counter), which emits a signal when the tracer, concentrated in the sentinel node, has been found. There may be from one to three sentinel lymph nodes. On average, two sentinel nodes are removed for biopsy.

Advantages and Uncertainties of Sentinel Node Biopsy Sentinel node biopsies have several advantages over axillary lymph node dissections. Because only a small number of lymph nodes are removed, a much smaller incision is required, the patient may be spared sometimes permanent postoperative complications, and the period of recovery is much shorter. An overnight hospital stay is not required, as it is with axillary lymph node dissection.

Metastasis to Other Areas of the Body

Cancer may spread to other areas of the body after it travels to the lymph nodes, or it may spread through the bloodstream to other regions of the body without first involving the lymph nodes. Breast cancer most often spreads to the bone, lung, and liver.

• Bone. About 25% of breast cancers spread first to the bone, generally the spine, ribs, pelvis, skull, arms, and legs.
• Lung. In 21% of breast cancer cases, the lung is the only place it spreads.
• Liver. Two-thirds of women with metastatic breast cancer eventually have it spread to the liver.

Breast cancer may also spread to the bone marrow, brain, ovaries, spinal cord, eye, and other areas.

Symptoms of Metastatic Breast Cancer

Symptoms of breast cancer that has spread may include:

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

Staging Breast Cancer

A cancer's stage describes the tumor and the extent to which it has spread in the body. After breast cancer has been diagnosed, cancer staging is a critical part of determining a patient's prognosis and the best treatment for her.

Imaging Tests for Staging

One or more of the following tests may be done to see if and how far the cancer has spread:

• Chest X-rays can determine if cancer has spread to the lungs.
• Mammograms give more detailed views of the breast.
• Bone scans help to see if cancer has spread to the bones. A small amount of low-level radioactive material is injected into a vein. The substance accumulates in areas of bone changes. A special camera that detects areas of radioactivity then takes pictures of the entire skeleton.
• Computed tomography (CT) scans can show if cancer has spread to the chest and/or abdomen. A CT scan uses X-rays to produce pictures of the body. The CT scanner rotates around the patient as she lies on a table, taking multiple images that are then combined by a computer into detailed cross-sectional "slices" of the area of the body being studied. Sometimes the patient may be given an oral or IV contrast dye to help outline structures of the body.
• Spiral (or helical) CT is faster than regular CT, and produces thinner and more detailed slices.
• CT-guided needle biopsy uses CT scans to guide the biopsy needle into the suspicious area. While the patient lies on the table, the doctor inserts the needle and repeats the scans until it is clear that the needle is in the mass.
• Positron emission tomography (PET) scans can help when it seems likely the cancer has spread, but it's unclear where. Radioactive glucose is injected into the body. Because cancer cells are very active, they absorb large amounts of the glucose. The radioactive areas show up on the PET scan.
• PET/CT scans combine PET with CT to show both structures of the body (CT) and its metabolism (PET). The radiologist can compare areas of higher radioactivity on the PET with the appearance of that area on the CT.
• Magnetic resonance imaging (MRI) scans, like CT scans, look for cancer in various parts of the body by producing slices of the area being studied and are particularly useful for looking at the brain and spinal cord. MRIs use magnets and radio waves, instead of X-rays, to make these images. A contrast material called gadolium may be injected. MRIs take longer than CT scans.
• Ultrasound can be used to look for cancerous masses in the abdomen or in the axillary lymph nodes. Ultrasound is better at finding large cancers in the lymph nodes than small ones. It may used along with mammography.

Clinical and Pathologic Staging

Breast cancer staging can be either clinical or pathologic. Clinical staging is based on the physical exam, biopsy, and imaging tests. Pathologic staging is based on all of those, plus the findings from surgery, after the pathologist has examined the breast tumor and the lymph nodes.

The TNM System of Cancer Staging

A staging system summarizes information about a cancer's spread. The most common system used to describe the stages of breast cancer is the TNM system, developed by the American Joint Committee on Cancer (AJCC).

• T stands for tumor. Numbers from 0 to 4 (eg, T1) indicate the tumor's size and the extent of its spread. Higher T numbers mean a larger tumor and/or wider spread to nearby tissues.
• N stands for nodes. Numbers from 0 to 3 indicate whether the cancer has spread to nearby lymph nodes and, if so, how many lymph nodes are involved.
• M stands for metastasis. The numbers 0 or 1 indicate if the cancer has spread to distant organs (eg, the lungs or liver).

Stage Grouping

When the TNM categories have been determined, the information is simplified by combining it into a stage. For instance, as seen in the table below, a T1, N0, M0 tumor would be considered Stage I breast cancer

Staging of Breast Cancer

Stage	Tumor	Node/Metastasis
0	Tis	N0/M0
I	T1	N0/M0
IIA	T0	N1/M0
	T1	N1/M0
	T2	N0/M0
	T2	N1/M0
	T3	N0/M0
		N1 (1 to 3 nodes)/M0
		N2 (4 to 9 nodes)/M0
		N2 (internal mammary nodes)/M0
IIIA	T0	N2/M0
	T1	N2/M0
	T2	N2/M0
	T3	N1/M0
	T3	N2/M0
IIIB	T4	N0/M0
	T4	N1/M0
	T4	N2/M0
IIIC	Any T	N3/M0
IV	Any T	Any N/M1

Tis = carcinoma in situ or Paget's disease of the nipple with no tumor Adapted from the American Joint Committee on Cancer, AJCC Cancer Staging Manual, Sixth Edition. New York, Sp