How to Navigate Metastatic Breast Cancer Test Results

In In The News by Barbara Jacoby


Metastatic breast cancer (MBC), also called stage 4 or advanced breast cancer, means that breast cancer has spread beyond the breast and nearby lymph nodes to other organs in the body, like the bones or brain.

Not all breast cancers are the same. If you’ve already received an MBC diagnosis, your doctor will most likely perform additional tests to help understand where in the body the cancer has spread, and to identify specific genes, proteins, and other factors unique to the tumor.

This information will help your healthcare team select the best treatment option. Certain treatments are more effective in breast cancers with a specific subtype, gene mutation, or other feature.

Tests for metastases

Your doctor will go over the results of imaging tests, such as bone scans, X-rays, MRIs, PET scans, and CT scans, to understand where and how the cancer has spread to other parts of your body.

An MRI, for example, is particularly useful to look at the brain and bones, while a CT scan can get a better picture of the chest, abdomen, or pelvis.

Understanding your MBC subtype

Standard testing of metastatic breast cancer looks at three key receptors. They’re proteins in or on the cells that attach to substances in the blood:

  • estrogen receptor (ER)
  • progesterone receptor (PR)
  • human epidermal growth factor receptor-2 (HER2)

Testing positive for ERs or PRs puts the cancer in a category called hormone receptor-positive (HR-positive). Your doctor may then classify the cancer into one of these subtypes:

  • HR-positive/HER2-negative
  • triple-positive (HR-positive/HER2-positive)

HR positive or negative

Hormone receptors include the estrogen and progesterone receptors. These are proteins that allow hormones like estrogen and progesterone to “feed” the cancer cells.

Hormone receptor status is either positive or negative. You may test positive for ER, PR, or both to be considered HR-positive.

According to, about 80 percent of breast cancers test positive for ER. Of those, about 65 percent of those are also positive for PR.

HER2 status

HER2 is a protein involved in cell growth that’s sometimes found on the outside of all breast cells. Breast tumors with higher than normal levels of this protein are referred to as HER2-positive tumors.

Triple negative

Triple-negative breast cancer means that the tumor is negative for HER2, ER, and PR. About 10 to 15 percent of breast cancers are triple-negative, according to the American Cancer Society.

Triple positive

Triple-positive breast cancer means that the tumor is positive for HER2, ER, and PR. In one 2019 study of 1,205 people with breast cancer, roughly 10 percent had triple-positive breast cancer.

Molecular testing

Your doctor may recommend lab tests on a sample of your tumor to identify factors, like gene mutations and proteins, that are unique to your tumor.

Your doctor may then use this information to help select a treatment. Some drugs work best when these proteins or gene mutations are present.


PD1/PD-L1 (programmed death-ligand 1) is a protein that may be found on breast cancer cells and some of the body’s immune cells.

This protein keeps immune cells from destroying the cancer. If you have this receptor and triple-negative breast cancer, adding immunotherapy drugs to standard chemotherapy may improve your outcome.

PIK3CA gene mutations

PIK3CA mutations are found in up to 40 percentTrusted Source of HR-positive, HER2-negative breast cancers. Your doctor may prescribe drugs that specifically target the PIK3CA gene if a PIK3CA mutation is found.

BRCA1 or 2 gene mutations

The BRCA1 and BRCA2 genes are involved in DNA repair. Tumors with mutations in either gene may respond to a newer class of drugs called PARP inhibitors. These drugs inhibit cancer cells from repairing their damaged DNA.

Next steps

Once you’ve received information about your HER2 and HR status and other genetic features of your tumor, it’s important to talk with your doctor about next steps. Your doctor will use this information to inform treatment decisions.

There may be a few different treatment options available for your specific tumor type. Your doctor will create a plan for you, but you have a say in which treatment you receive.

Writing notes before your appointment can help you remember what you want to talk about. You may want to also come prepared with a few questions, such as:

  • What are the possible side effects of treatment?
  • How will the treatment affect my quality of life?
  • What other treatment options are available, and what are the advantages/disadvantages of each?
  • What happens if I delay treatment?
  • Are there clinical trials available or upcoming new medications that may be an option for my tumor type?
Treatment options

While MBC doesn’t have a current cure, treatments are available to help prolong your life. The goal of treatment is to manage symptoms and keep the cancer from spreading further.

Hormone therapy

Anti-estrogen therapy, such as tamoxifen, fulvestrant (Faslodex), or aromatase inhibitors, are recommended to treat HR-positive cancers. Hormone therapy helps prevent estrogen from feeding cancer cell growth.

Side effects of hormone therapy may include:

  • hot flashes
  • fatigue
  • mood changes
  • vaginal dryness
  • muscle pain
  • joint stiffness


You doctor may recommend chemotherapy, especially if your tumor is triple-negative and won’t respond to hormone therapies.

Chemotherapy can have many side effects, including:

  • anemia
  • diarrhea
  • fatigue
  • hair loss
  • loss of appetite
  • mouth sores
  • nausea

Keep in mind that not all chemotherapy used to treat MBC causes hair loss.

Targeted therapy

Targeted therapies specifically target the changes in cells that cause abnormal cell growth. Targeted therapies, such as trastuzumab or pertuzumab, may be used together with chemotherapy for HER2-positive breast cancer.

Other targeted therapies for HER2-positive breast cancer include:

  • ado-trastuzumab emtansine (Kadcyla)
  • fam-trastuzumab deruxtecan (Enhertu)
  • kinase inhibitors, including lapatinib (Tykerb), tucatinib (Tukysa), or neratinib (Nerlynx)

For HR-positive breast cancers, the following targeted therapies may be used to make hormone therapy more effective:

  • cyclin-dependent kinase 4/6 inhibitors, such as palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio)
  • everolimus (Afinitor), an mTOR inhibitor
  • alpelisib (Piqray), which is a PI3K inhibitor

Your doctor may prescribe other targeted agents for BRCA gene mutations, including olaparib (Lynparza) and talazoparib (Talzenna). These are classified as PARP inhibitors.

Side effects of these treatments are generally mild but may include:

  • diarrhea
  • headache
  • heart problems
  • infection
  • liver problems
  • loss of appetite
  • low blood cell and platelet counts
  • nausea


Radiation can help shrink tumors that have spread to other parts of the body. It’s typically used to help decrease pain and other symptoms.


If the cancer has already spread, surgery may not be a good treatment choice because it may not get rid of all the cancer.


Immunotherapy is the use of treatments to stimulate a person’s own immune system to recognize and destroy cancer cells more effectively.

New immunotherapies that target PD1/PD-L1, such as pembrolizumab (Keytruda) and atezolizumab (Tecentriq), have been shown to be successful for the triple-negative subtype.

Side effects of immunotherapies may include:

  • autoimmune reactions
  • fatigue
  • infusion reactions
  • nausea
  • poor appetite
Symptom management

MBC can cause a wide range of symptoms, including:

  • abdominal pain or bloating
  • chest pain
  • constant dry cough
  • difficulty breathing
  • loss of appetite
  • loss of balance
  • nausea, vomiting, or weight loss
  • numbness or weakness, anywhere in the body

Other symptoms may depend on where in the body the cancer has spread. For example:

  • Bone metastases may cause sudden pain and increased risk of fractures.
  • Brain metastases can lead to headaches, changes in speech, vision changes, and memory problems.
  • Lung metastases can cause shortness of breath and cough.
  • Liver metastases may cause fatigue, weakness, and poor appetite.

Treatment to relieve symptoms may include:

  • anti-nausea medications
  • pain medications
  • psychological support or counseling
  • radiation, surgery, or both to remove metastases that may be putting pressure on a nerve or the spinal cord
The takeaway

The results of laboratory and genetic testing for MBC are used to determine the best options for treating your cancer. The use of more targeted therapies has greatly improved the outlook for metastatic disease.

Once you understand your specific subtype, you can talk with your doctor about which treatments or combinations of treatments will likely be the most effective.