Advanced Breast Cancer

Overview & staging

Advanced breast cancer is breast cancer that has spread beyond the breast, chest wall and nearby lymph nodes, such as the liver, lung, bone or distant lymph nodes. Advanced breast cancer is most often diagnosed when an earlier stage breast cancer returns or recurs months or even decades later, but it can also be identified at initial diagnosis.

This content explores Stage IV (also called metastatic) breast cancer and discusses triple-negative breast cancer and inflammatory breast cancer. Additionally, while Stage III cancers are considered locally advanced and are treated with curative intent, some of the information provided for metastatic disease may be helpful for people with this diagnosis. Because a cure is not yet available for Stage IV breast cancer, the goal is to identify the treatment that works best for each patient. Ongoing advances in research are resulting in treatments that enable many people with advanced breast cancer to live longer and with a better quality of life than ever before.

When you’re faced with an advanced breast cancer diagnosis, knowledge is empowering. This content is filled with valuable resources that will help you better manage your disease. Read on to learn more about the types of advanced breast cancer, recommended treatments, side effects and clinical trials, along with helpful tips and support resources for you, your caregiver and your loved ones.

Development of metastasis

Stage IV breast cancer is also called metastatic or advanced breast cancer. When breast cancer spreads, it typically lands in the bones, liver, lungs or brain. Where a cancer starts, or its primary site, often plays a role in where it will metastasize, or spread. Most cancer cells that break free from the original tumor are carried in the blood or lymph until they get trapped in the next “downstream” organ or set of lymph nodes. Once the cells are there, they either die or start new tumors. This is why breast cancer often spreads to lymph nodes in the underarm but rarely to lymph nodes in the groin.

Metastasis is often found during follow-up appointments or during evaluation of symptoms such as bone pain, persistent cough or shortness of breath. An advanced breast cancer diagnosis is made when new cancerous lesions are discovered far from the primary site. Although the cancer has spread to another part of the body, the cancer is still considered breast cancer and will be targeted with the breast cancer treatments you decide on with your doctor.


Staging determines the extent of the cancer based on the size of the original tumor and if it has spread (see Figures 1 and 2). The staging system used for most cancers is called TNM staging and was developed by the American Joint Committee on Cancer (AJCC) (see Tables 1 and 2).

Table 1. AJCC system for classifying breast cancers

Category Definition
Tumor (T)
Tx The tumor cannot be assessed.
T0 No evidence or primary tumor.
Tis Known as carcinoma in situ, the tumor has not started growing into the breast tissue. 
Tumor is 2 centimeters (about ¾ inch) or less.
Tumor is 1 millimeter or less.
Tumor is larger than 1 mm but not more than 5 mm (0.5 cm).
Tumor is larger than 5 mm but not more than 10 mm (1 cm).
Tumor is larger than 10 mm but not more than 2 cm.
T2 Tumor is larger than 2 cm but not more than 5 cm (almost 2 inches).
T3 Tumor is larger than 5 cm.


Tumor may be any size but has grown into the chest wall and/or to the skin.
Tumor extends into the chest wall.
The skin shows the presence of one or more of the following: edema (swelling), ulceration (a sore, painful area where the breast skin/tissue is breaking down), or satellite skin nodules (additional tumor cell masses) in the same breast.
Signs of both T4a and T4b are present.
Breast is red, swollen and warm, indicating inflammatory carcinoma.
Nodes (N)
Nx Lymph nodes cannot be evaluated.
N0 No metastasis or micrometastasis* found in any lymph nodes.




Micrometastases* are found in lymph nodes (more than 0.2 mm but no more than 2 mm).
Cancer cells have spread to 1 to 3 axillary lymph nodes (nodes under the arm), with at least one metastasis of more than 2 mm (0.2 cm).
Cancer cells have spread to internal mammary lymph nodes (nodes on either side of the sternum [breastbone]), not detected by physical exam or imaging.
Cancer cells have spread to 1 to 3 axillary lymph nodes and in internal mammary lymph nodes.

Cancer cells have spread to 4 to 9 axillary lymph nodes.
Cancer cells have spread to clinically detected internal mammary lymph nodes but not to axillary lymph nodes.



Cancer cells have spread to 10 or more axillary lymph nodes OR to the infraclavicular lymph nodes (nodes under the clavicle [collarbone]).

Cancer cells have spread to clinically detected internal mammary lymph nodes and to 1 or more axillary lymph nodes.

Cancer cells have spread to supraclavicular lymph nodes (nodes above the clavicle).
Metastasis (M)
M0 Cancer has not spread to other parts of the body (beyond the breast and local lymph nodes).
cM0(i+) There is no evidence of cancer spread, but deposits of tumor cells can be detected at the microscopic or molecular level in the blood, bone marrow or other nodal tissue.
M1 There is clinical evidence that cancer has spread to other parts of the body.

*Refers to a small cluster of tumor cells, no larger than 2 millimeters.

Table 2. Stages of breast cancer

Stage TNM classifications
IIIA T0-T3, N2, M0 // T3, N1, M0
IIIB T4, N0-N2, M0
IIIC Any T, N3, M0
IV Any T, Any N, M1


Figure 1

Figure 2

Once advanced breast cancer is diagnosed, the AJCC also recommends testing for estrogen and progesterone receptors (ER and PR) and human epidermal growth factor receptor-2 (HER2):

  • Estrogen receptor (ER) - if ER receptors are present in your cancer cells, they may receive signals from estrogen that promote their growth.
  • Progesterone receptor (PR) - if PR receptors are present in your cancer cells, they may receive signals from progesterone that promote their growth.
  • Human epidermal growth factor receptor 2 (HER2) - a protein found on the surface of breast cells that normally helps control how a healthy breast cell grows, divides and repairs itself. In about 25 percent of breast cancers, this gene makes too many copies of itself, resulting in the breast cells growing and dividing in an uncontrolled way.

Your cancer will respond to types of treatment differently depending on the presence of ER, PR and HER2, so this information is critical in helping your doctor recommend the type of treatment best for you (see Table 3).

Most patients with metastatic breast cancer have HER2-negative (HER2-) breast cancer. If your HER2- breast cancer is also hormone receptor-positive (ER+ and PR+), the most common treatment is hormone therapy, but chemotherapy and targeted therapy also are options. If you have ER+, PR+ or HER2+ breast cancer, your doctor may recommend medicines to shrink, slow or stop the cancer cell growth.

Table 3. Receptor and treatment response

Receptors 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

Less common types of breast cancer

A triple-negative breast cancer (TNBC) diagnosis means that the tumor tests negative for the estrogen receptor (ER-), progesterone receptor (PR-) and human epidermal growth factor (HER2-). As a result, TNBC does not respond to the hormone or targeted therapies typically used to treat advanced breast cancer, so chemotherapy is the only treatment option. Because of this, TNBC can be more difficult to treat, as the average length of time that tumors respond to chemotherapy is shorter than for other types of breast cancer.

More about TNBC:

  • About 10 to 20 percent of breast cancers are triple-negative.
  • TNBC is more common in younger women or those of African/African American descent.
  • There is a higher chance of carrying an inherited mutation in BRCA1 (BR stands for BReast, CA stands for CAncer). Gene mutations are associated with a family risk of breast and ovarian cancers. It is recommended that all patients with TNBC under age 60, even without a family history of cancer, be tested for BRCA 1 and 2. If you are unsure whether you carry the BRCA1 gene, talk with your doctor about genetic testing, as it can help identify treatments that will be most successful for you.

TNBC is an ongoing focus of intensive research for patients with and without the BRCA1 mutation. Triple-negative cancers have a very high level of DNA damage. To develop treatments that repair DNA damage, researchers are evaluating targeted drugs such as poly (ADP-ribose) polymerase (PARP) inhibitors, a family of enzymes needed for a type of DNA repair. Clinical trials are providing enough positive findings to encourage ongoing research, and other targeted and combination therapy drugs also are being evaluated. When you discuss treatment options with your doctor, ask about available clinical trials that you may be eligible for (see "Clinical trials" in Treatment Strategies).

Inflammatory breast cancer (IBC) is a rare and very aggressive disease in which cancer cells block the lymph vessels in the skin. Named because the breast often looks red or inflamed and feels warm, IBC also may give the breast skin a thick, pitted appearance that resembles an orange peel.

Most inflammatory breast cancers are invasive ductal carcinomas, which means they developed from cells that line the milk ducts of the breast and then spread beyond the ducts. IBC progresses rapidly and is always staged as at least Stage IIIB (locally advanced) when first diagnosed because the breast cancer cells have metastasized into the skin. If it has spread to the lymph nodes, surrounding tissues or other body parts, it is diagnosed as Stage IV. The advanced stage of IBC, along with its tendency to grow and spread quickly (sometimes in a matter of weeks or months), makes it more challenging to treat than most other types of breast cancer.

IBC accounts for about 1 to 5 percent of all breast cancers. Some experts believe it actually may be more common, but diagnosing it can be difficult because of its atypical symptoms. Breast lumps are not common, and IBC might not show up on a mammogram. Additionally, the swelling and tenderness often lead to a misdiagnosis of mastitis, an infection of the breast tissue that is accompanied by breast pain, swelling, warmth and redness.

More about IBC:

  • IBC is more common and is diagnosed at a younger age than other types of breast cancer. It is also diagnosed at a younger age in African American women (average age, 52 years) than in Caucasian women (average age, 57 years). Obesity is also a risk factor.
  • Treatment usually includes a combination of chemotherapy drugs, surgery and radiation therapy. Inflammatory breast tumors are frequently hormone receptor-negative, which means that hormone therapy may not be an effective strategy.
  • Like other types of breast cancer, IBC can occur in men, but it is usually diagnosed at an older age (after 67 years) than in women.

Because IBC is rare, patients are encouraged to take part in clinical trials for access to the most leading-edge treatments. To learn more about clinical trials and where to find information about available trials, see "Clinical trials" in Treatment Strategies.


Advanced breast cancer in men

Breast cancer in men is a rare disease that occurs when malignant cells invade the breast tissue. Although breast cancer can be diagnosed in men at any age, the average age at diagnosis is between 65 and 70 years.

Even though men have less breast tissue than women, making a lump easier to feel, men may ignore breast changes or not report them to their doctor because they don’t realize they are at risk. As a result, breast cancer in men is often diagnosed at a late stage. That delay in diagnosis can allow the cancer to spread to lymph nodes under the arm or around the collar bone, even before the original tumor in the breast tissue is large enough to be felt.

Most breast cancers in men are hormone receptor-positive, meaning that the growth of cancer cells is stimulated by estrogen and/or progesterone. Typical treatments for hormone receptor-positive cancers include the following:

  • Surgery to remove the tumor
  • Chemotherapy to kill the cancer cells
  • Hormone treatment to stop cancer cell growth
  • Radiation treatment to help reduce the risk of recurrence, relieve symptoms and avoid complications from areas of metastases

Because so few men are diagnosed, fewer clinical trials have studied breast cancer in men than in women, but researchers are investigating ways to treat the disease in men. Most treatments for men are modeled on treatments for women because the disease tends to respond similarly in both men and women. Talk with your doctor about each type of treatment, potential side effects and clinical trials so you can make an informed treatment decision.

When a man hears his diagnosis, his shock at learning he has cancer is often compounded by embarrassment at having what is traditionally known as a “woman’s disease.” It is crucial to remember that you’re not alone. Your feelings are valid. Discussing them and comparing notes with other men going through similar experiences can be immensely helpful. See Additional Resources, and talk with your treatment team about support groups and other resources.


Additional Resources




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