What is Advanced, Metastatic and Stage 3 & 4 Breast Cancer?

If you or a loved one has been diagnosed with advanced or metastatic breast cancer, understanding the disease is a first step to finding the best treatment option. Use these resources to learn about the different types of breast cancer, the treatment options available, and how to get the most of the time with the doctor.

What is advanced or metastatic breast cancer?

Breast cancer begins when abnormal cancerous cells in the breast grow and multiply without stopping, creating a tumor. It usually starts in the ducts or lobules of the breast.

Advanced breast cancer includes the most serious of the five possible stages, Stages 3 and 4. Stage 3 is locally advanced breast cancer, which means the cancer has spread to lymph nodes and/or other tissue in the breast, but not to further sites in the body. Stage 4 is metastatic breast cancer. At this stage, the cancer has spread to other sites of the body, such as the liver, lungs, bones, brain, and/or others.

Advanced Breast Cancer 101

Advanced Breast Cancer 101


What type of advanced breast cancer do you have?

Advanced Breast Cancer 101

Dr. Fatima Cardoso, MD: Getting to Know the Types of Advanced Breast Cancer

Your doctor should test your cancer to determine what type of advanced breast cancer you have. This will help your doctor and you know what type of treatment may be best for you.


Cancer gets many signals that drive its growth.

These signals may take the form of hormones. Hormone receptors are proteins that pick up hormone signals and tell the cancer cells to grow. If your type of breast cancer gets signals from the hormone estrogen that could promote tumor growth, it is known as estrogen receptor-positive (ER+) breast cancer. If your type of breast cancer gets signals from the hormone progesterone that could promote growth, it is known as progesterone receptor-positive (PR+) breast cancer. Breast cancer that is ER+ or PR+ falls under the category of hormone receptor-positive (HR+) breast cancer.

Another category of breast cancer is called hormone receptor-negative (HR-). This type of breast cancer has cells without hormone receptors. HR- breast cancer cells do not depend on estrogen or progesterone to grow.

Human epidermal growth factor receptor-2 (HER2) is a gene that helps control how cells grow, divide, and repair themselves.


The HER2 gene makes HER2 proteins.

These proteins are receptors on breast cells. Human epidermal growth factor receptor-2 positive (HER2+) is a breast cancer that tests positive for the HER2 protein. HER2+ breast cancer tends to grow faster and is more likely to spread and come back compared to human epidermal growth factor receptor-2 negative (HER2-) breast cancer. Your HER2 status is determined by whether your breast cancer tests positive or negative for the HER2 protein.

If your pathology report comes back negative for estrogen receptors (ER-), progesterone receptors (PR-), and human epidermal growth factor receptor-2 (HER2-), then your disease is known as "triple negative" breast cancer. This means that your breast cancer does not depend on hormones or HER2 proteins to grow.

HER2 and HR statuses can change from the original cancer, so cancer cells should be retested whenever breast cancer comes back or spreads to a new site in the body.

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HR+/HER2+ breast cancer is also called Luminal B breast cancer. HER2+ breast cancer means your breast cancer has tested positive for a protein called human epidermal growth factor receptor-2 (HER2), which promotes cancer cell growth. This happens in about 1 of every 5 breast cancers, when the cancer cells make an excess of HER2 due to a gene mutation.

When breast cancer is HR+, the cancer can be treated with hormone therapies that block the hormones from the cancer cells. HER2+ cancer tends to be less responsive to hormonal treatment. This could be because HER2+ breast cancer tends to be more aggressive than other types of breast cancer. However, treatments that specifically target HER2 can be effective.


HR+/HER2- breast cancer, also called Luminal A, is the most common form of breast cancer. This type accounts for more than 70% of all breast cancers. HR+ cancer is usually treated with hormone therapies or a combination of a hormone therapy with a targeted therapy to help stop tumor growth first. Hormone therapies help prevent the cancer cells from getting the estrogen they need to grow. HR+ tumors have a slightly lower chance of breast cancer coming back in the first five years after diagnosis than HR- tumors. However, sometimes the cancer outsmarts the treatment and becomes resistant to hormonal therapy and stops working.


HR-/HER2+ advanced breast cancer commonly has the characteristics of inflammatory breast cancer (IBC). HR- breast cancers do not respond to hormonal therapies, and HER2+ tumors tend to be more aggressive. Therefore, HR-/HER2+ is usually treated with multiple types of treatment, including chemotherapy and targeted HER2+ treatments, but not hormonal therapies.

More on Inflammatory Breast Cancer:
Most IBC cases are invasive ductal carcinomas, meaning that the cancer develops from cells that line the milk ducts of the breast and then spread beyond the ducts, and tend to be initially diagnosed as advanced. IBC accounts for 1-5% percent of breast cancers diagnosed in the United States, and commonly are diagnosed at younger ages (median age of 57 years, compared with a median age of 62 years for other types of breast cancer). IBC is not always HR-/HER2+, so talking to your doctor about your type of breast cancer is still recommended.


HR-/HER2- or HR-/HER2-/PR- advanced breast cancer is also called Triple Negative Breast Cancer (TNBC), as the tumor is negative for both estrogen and progesterone receptors, and does not overexpress the gene HER2. About 15-20% of all breast cancers are TNBC. Anyone can get this type of breast cancer, but research shows that it occurs more often in younger women, African American women and women who have the BRCA1 mutation.

Triple negative tumors can be aggressive and may have a poorer prognosis (at least within the first five years after diagnosis) compared to HR+ types of the disease. TNBC is usually treated with some combination of surgery, radiation therapy, and chemotherapy. These tumors cannot be treated with hormone therapies or HER2 targeted therapies because they are HR- and HER2-. Research is currently underway to learn how to target other pathways in triple negative tumors. See here for more information on clinical trials.


Know the Different Types of Treatment

Cancer research is always evolving, and new medicines are continuously being developed. Currently, there is no cure for advanced or metastatic breast cancer, so staying up-to-date about new treatments and talking to your doctor about your options may help you live the best life possible.

There is not a single treatment approach that works the same way for everyone living with advanced or metastatic breast cancer. Some people may receive a combination of therapies, while others may receive only one therapy at a time.

When your first therapy stops working or is discontinued, your doctor will recommend a new therapy, often referred to as a new “line of treatment.” For most patients, the first line of treatment is the most effective and the longest lasting.

Your first line of treatment should be chosen carefully because that’s when a treatment can be most successful in delaying cancer progression. Your physician should help customize your treatment plan to meet your needs and your individual situation.

How does your doctor measure if your treatment is working?

To determine if your treatment is working, your doctor may conduct a number of assessments, such as:

Advanced Breast Cancer 101

Advanced Breast Cancer Treatments

  • Tumor size: Your doctor will use tests such as computed tomography (CT) or magnetic resonance imaging (MRI) scans to measure whether your tumor is growing, shrinking, or staying the same size.
  • Tumor markers: Tumor markers are proteins or other substances that are found in the blood or urine when tumors are active in the body. The presence of elevated tumor markers can indicate active disease.
  • New metastasis: If tumor cells take hold in another part of the body, it is an indication that treatment isn't working.

Hormonal Therapy

There are different types of advanced breast cancer. In some types, the hormones estrogen or progesterone can promote the growth and spread of the tumor. Your doctor may refer to this as hormone receptor-positive (HR+) breast cancer.

Hormonal treatment, also called endocrine therapy, blocks estrogen and stops it from driving cancer progression. This kind of treatment is a primary treatment for HR+ advanced breast cancer. For many, it helps control the cancer and prevents it from getting worse for a period of time.

There are many types of hormonal treatments, including therapies known as aromatase inhibitors, selective estrogen receptor modulators and estrogen receptor downregulators. Some block estrogen directly whereas others shut down production of estrogen from the ovaries.

If you have HR+ advanced breast cancer, there may be other drugs that can be added to your hormonal therapy. These drugs work to block certain protein cells. Blocking these cells helps stop cancer cells from growing and/or dividing to make new cells, which may slow cancer growth and progression. Learn more about these by clicking on the “combination therapy” tab to the left.

Talk to doctor about the different treatment options and which ones may be best for you.

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Targeted Therapy

Targeted therapies are treatments designed to identify and attack (or "target") specific characteristics of cancer cells. Such therapies focus on certain molecules that are known to be involved in tumor growth and spread; these molecules are also present in normal, healthy cells. Your doctor may refer to these types of therapies as "molecular-targeted drugs," "molecularly targeted therapies" or “immune targeted therapies.” These treatments may also affect healthy, non-tumor cells.

Targeted therapies may be given alone (monotherapy), or in combination with either hormonal treatment or chemotherapy (combination therapy). Learn more about hormonal therapy, chemotherapy or combination therapy by clicking on the tabs to the left.

Talk to your doctor about the different treatment options and which ones may be best for you.

Additional Information

Combination Therapy and CDK4/6 inhibitors

Researchers developed treatments that can be added to hormonal therapy as one possible way to stop cancer from growing for a longer period of time than hormonal therapy alone. One group of these treatments are medicines called CDK4/6 inhibitors.

CDK stands for cyclin-dependent kinases, which are a family of proteins found in all cells in the body. CDKs are important in controlling the normal life cycle of cells as they grow and divide into new cells. CDK4/6 inhibitors work by interfering with the kinases and preventing cells from multiplying.

CDK4/6 inhibitors work in combination with hormonal therapy to slow cancer progression by reducing cancer growth.

Other pathways continue to be topics of research, which may lead to additional combination therapies in the future.

Talk to your doctor about the different treatment options and their side effect profiles and which ones may be best for you.

Additional Information

Biological Therapy

Biological therapies use the body's immune system to fight cancer or to lower the side effects that may be caused by some cancer treatments. Biological response modifiers (BRMs) occur naturally in the body and can be produced in the laboratory. BRMs change the interaction between the body's immune defenses and cancer cells to boost, direct, or restore the body's own ability to fight the disease.

Biological therapies include interferons, interleukins, colony-stimulating factors, monoclonal antibodies, vaccines, gene therapy, and nonspecific immunomodulating agents. A nonspecific immunomodulating agent is a substance that stimulates the immune system in a general way and boosts the body's ability to fight cancer, infection, or other diseases.

Talk to your doctor about the different treatment options and which ones may be best for you.

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Chemotherapy is the use of drugs to kill cancer cells. Some ways that chemotheraphy may be given are by mouth (orally) or infused into a vein (intravenously). It is usually given in cycles. A cycle includes treatment days that are followed by periods of rest. Treatment generally does not require a hospital stay; it is often given in an outpatient or clinical setting.

In advanced or metastatic breast cancer, chemotherapy is usually given to people with HR+ disease who have become resistant to hormonal treatment (hormonal treatment stops working) or to people who have triple-negative advanced breast cancer. It can also be given to some people who have HR- and HER2+ disease. People with life-threatening metastases may also receive chemotherapy. Chemotherapy may be prescribed as neoadjuvant (before surgery to remove a tumor) or adjuvant (after surgery to remove a tumor) therapy.

Chemotherapy can shrink tumors relatively quickly. Chemotherapy destroys both cancer cells and healthy cells. Chemotherapy may also be combined with other therapies to improve tumor response.

Read through the information below to get a better understanding of chemotherapy, including treatment, side effects, support, and questions you may want to ask your doctor.

Additional Information


Immunotherapy is a type of biological therapy that is currently being investigated for the treatment of advanced or metastatic breast cancer. Immunotherapy uses the body's own immune system to fight cancer. It works by either stimulating your immune system to attack cancer cells or giving your immune system what it needs, such as antibodies, to fight cancer. Immunotherapy may be used alone or with other treatments, such as radiation, chemotherapy, or targeted therapy.

Talk to your doctor about whether immunotherapy is a treatment you should consider and about possible clinical trials that may be right for you.

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Radiation therapy (also called radiotherapy) uses high-energy rays to kill cancer cells. Radiation for advanced or metastatic breast cancer is largely done to reduce pain from bone metastases, which may relieve symptoms and may reduce specific spots where the cancer has spread.

Talk to your doctor about the different treatment options and which ones may be best for you.

Additional Information


Surgery is often the first line of attack against early-stage breast cancer. Most people with early-stage breast cancer will have surgery to remove their tumor. The two most common kinds of surgery for breast cancer patients are a mastectomy or lumpectomy. However, surgery for people living with advanced or metastatic breast cancer is not always part of their treatment plan. You should consult your doctor to determine the best treatment approach for your individual situation.

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Clinical Trials

Research is ongoing and new treatments are constantly being developed and studied. If you have been diagnosed with advanced or metastatic breast cancer, you can talk to your doctor about the possibility of joining a clinical trial. Your doctor should be able to tell you which clinical trials you might qualify for and those that are available in your area.

In clinical trials, researchers use a number of assessments to determine whether treatments are effective in helping to control cancer, such as:

  • Progression-free survival, or PFS, is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse, according to the NCI.
  • Overall survival, or OS, is the length of time a person lives after being diagnosed with a life-threatening disease, such as cancer, until death from any cause, according to the National Cancer Institute (NCI).
  • Overall response rate to medication is the percentage of people whose cancer shrinks or disappears after treatment.
  • Clinical benefit rate is the percentage of patients who achieve a complete response, partial response, or stable disease. These measurements indicate how a tumor responds to treatment.
  • Improvement in quality of life is an increase in a person's overall enjoyment of life, according to the NCI.

Tune into this video to hear more about clinical trials from advocate Eliza Adams.

Complementary & Alternative Medicine

Complementary and alternative medicine (CAM), as defined by the National Center for Complementary and Alternative Medicine (NCCAM), is a group of diverse medical and healthcare systems, practices, and products that are not presently considered to be part of conventional medicine. Complementary medicine can be used together with conventional medicine. Alternative medicine can be used in place of conventional medicine. Conventional medicine is medicine as practiced by holders of MD (medical doctor) or DO (doctor of osteopathy) degrees and by their allied health professionals, including physical therapists, psychologists, and registered nurses. Other terms for conventional medicine include allopathy, Western, mainstream, orthodox, regular medicine, and biomedicine.

Talk to your doctor about the different treatment options and which ones may be best for you.

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Make Your Dialogue Count

The average doctor’s appointment only lasts 15 minutes. Not surprisingly, a global survey found that women wish they had more time with their doctor to discuss their needs.

The US-based Make Your Dialogue Count survey sought to better understand how patients, caregivers, and doctors can improve their conversations. As a result of the survey, the Make Your Dialogue Count personalized discussion guide was developed as a tool to help women focus their conversations on what is most important to them.

Check out some of the findings from the Make Your Dialogue Count survey below as well as more information on the Make Your Dialogue Count personalized discussion guide.

Make Your Dialogue Count Personalized Discussion Guide

To help you get the most out of your time with your physicians, we developed the Make Your Dialogue Count personalized discussion guide.

By answering six questions about your advanced breast cancer, you will get a personalized discussion guide that addresses your unique situation and concerns, along with tips and questions to ask your doctor. You can retake the questionnaire and get a new discussion guide whenever your treatment, status, or needs change.

For general tips on talking about advanced breast cancer with your doctor, click here for tip sheets in different languages.

Survey Results

As shown in the Count Us global survey, women with advanced breast cancer wish they had more time to discuss their needs during doctor's visits. While you can't always control the amount of time you have, you can make that time count. In addition, an advisory board of physicians, patient advocates and a psycho-oncologist partnered with Novartis to commission a survey of 359 women living with advanced breast cancer, 252 oncologists and 234 caregivers in the United States to better understand how patients and doctors can improve their treatment communications.

See what survey respondents said about their experiences.

It's important to receive emotional support throughout your journey to help you cope with your diagnosis.

7 out of 10

patients said it’s important for their doctor to refer them to support services at the time of their initial advanced or metastatic breast cancer diagnosis, but

Only 36%

reported that this was something their doctor did

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Ask your doctor which services he or she recommends in your community. You may find support from licensed professionals, advocacy organizations, or through support groups (in-person or online).

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Watch this video for more information on the importance of psychological support and visit the resources page on this site to get more information about support services.

Receiving an advanced or metastatic breast cancer diagnosis can be overwhelming. Your treatment goals may differ from those of other women, so it's important to share them with your treatment team.


of patients said it’s important for their doctor to discuss long-term treatment goals (e.g., managing pain, keeping hair, extending life for as long as possible, attending a wedding/the birth of a grandchild), but

Only 53%

reported that discussing long-term treatment goals was something done at their diagnosis

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If you still have questions after your initial doctor's visit, schedule a follow-up appointment or speak to your doctor by phone. It's a good idea to write down your goals and questions ahead of time. Here are some you can consider:

Cancer research is always evolving with new medicines continually in development. It's important for you to be an active participant with your healthcare provider when discussing your treatment goals.


of patients strongly agreed that they felt their doctor sufficiently educated them about the options available before they began their most recent treatment, but

Only 48%

of patients strongly agreed that they felt their doctor provided them with enough information about the treatment options that may become available in the future

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Knowing your type of breast cancer and options for managing side effects will help you and your oncologist choose the right treatment plan for you. The Make Your Dialogue Count personalized discussion guide can help you focus your conversations on what is most important to you.

It's important for your doctor to discuss expectations for treatment with you. That said, not all treatments work the same on every patient, so your doctor cannot know with certainty how well the treatment will work or what impact it will have on your daily life.


of patients said it’s important for their doctor to discuss expectations of how well the recommended treatment will work, but

Only 72%

reported that this was something their doctor did

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There are questions you can ask to help guide this discussion and to get a better understanding of your treatment. See some suggestions here:

Potential side effects are different across treatments, and because each treatment affects people differently, it is unclear who will experience side effects and who will not. Side effects do not necessarily indicate that a treatment is or is not working. It's important to talk to your doctor about the potential side effects of any treatment you are considering.


of caregivers said their loved one hasn't spoken to her doctor about side effects because she felt like they are just something she had to live with


of patients wish their doctor did more to proactively manage side effects

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There are ways to proactively manage some side effects. As you start treatment, ask your doctor if there are ways to minimize side effects. If you do experience side effects, tell your doctor or treatment team — they may be able to offer ideas for relief or alter your dosing to address side effects.

You and your doctors and nurses all want to find ways to manage side effects.


of oncologists wish they could do more to help their patients manage their side effects


of patients agreed they want more information on how to prevent or minimize side effects

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It may be worth doing your own research (looking on accredited websites, discussing at an advocacy support meeting, asking other people living with the disease) and discussing what you find with your doctor. Your treatment team may also have suggestions for helping to manage side effects. Regardless, it's important to discuss any side effects that you may be experiencing with your doctor or nurse.