Other Breast Cancer Gene, Protein, and Blood Tests

When breast cancer is diagnosed, samples that have been collected during biopsies, bloodwork, or other tests are sent to a pathology lab. A pathologist, a doctor who uses lab tests to diagnose diseases such as cancer, will look at the samples and may do other special tests to help better classify the cancer. These tests can also help choose certain drugs that might work better for your cancer. This is sometimes called precision or personalized medicine because it is precise (or specific) for the features of your cancer.

The results of these tests are described in a pathology report, which is usually available within a week or two. If you have any questions about your pathology results or any diagnostic tests, talk to your doctor. If needed, you can get a second opinion of your pathology report by having your tissue samples sent to a pathologist at another lab.

Tests for certain proteins on tumor cells

Lab tests might be done to look for certain proteins on the cancer cells.

Hormone receptor proteins: All breast cancers are tested for hormone receptors (proteins). Specifically, the cancer is tested for estrogen receptor (ER) and progesterone receptor (PR). Read more at Breast Cancer Hormone Receptor Status.

HER2 protein: All invasive breast cancers are tested for the HER2 protein to see if too much is being made. If it is not clear how much HER2 protein is present, molecular testing might be done to see how many copies of the HER2 gene the cancer cells have. For more information about the HER2 gene and protein see Breast Cancer HER2 Status.

PD-L1 protein: People with advanced or metastatic triple-negative breast cancer might have their cancer tissue tested for the PD-L1 protein, which can show if the cancer is more likely to respond to treatment with certain immunotherapy drugs along with chemotherapy. 

Molecular tests for gene changes

In some cases, doctors may test for specific gene changes in the breast cancer cells that could mean certain targeted drugs or immunotherapy drugs might help treat the cancer.

These molecular tests (also known as genomic tests or biomarker tests) can be done on tissue taken during a biopsy or surgery for breast cancer. If the biopsy sample is too small and all the molecular tests cannot be done, the testing may also be done on blood that is taken from a vein just like a regular blood draw. This blood contains the DNA from dead tumor cells (known as circulating tumor DNA, or ctDNA). Obtaining the tumor DNA through a blood draw is sometimes called a "liquid biopsy" and can have advantages over a standard needle biopsy, which can carry risks.

Some changes that might be tested for include:

• BRCA1 and BRCA2 gene mutations: For women with an advanced HER2-negative breast cancer, your doctor might test you (not your cancer cells) for a hereditary BRCA1 or BRCA2 mutation (gene change). If you have one of these gene changes, treatment with the targeted drugs, olaparib (Lynparza) or talazoparib (Talzenna) might be options.
• PIK3CA, AKT1, and PTEN gene mutations: These 3 genes code for proteins in the same signaling pathway inside cells that can help them grow. Cancer cells sometimes have changes in one of these genes. If you have advanced breast cancer that is hormone receptor-positive and HER2-negative, and if the cancer cells show changes in one of these genes, a targeted drug such as capivasertib (Truqap) or alpelisib (Piqray) might be an option, along with the hormone drug fulvestrant.
• ESR1 gene mutations: The ESR1 gene contains the cell’s instructions for the estrogen receptor (ER) protein. Mutations in this gene can make breast cancers less likely to be helped by some forms of hormone therapy. But for advanced breast cancer, the hormone drug elacestrant (Orserdu) may be helpful if the cancer cells have an ESR1 mutation. This gene change can be tested for in a sample of your blood.
• MSI and MMR testing: Breast cancer cells might be tested to see if they show high levels of gene changes called microsatellite instability (MSI). Testing might also be done to see if the cancer cells have changes in any of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2). Breast cancer cells that have a high level of microsatellite instability (MSI-H) or a defect in a mismatch repair gene (dMMR) might be treated with the immunotherapy drugs, pembrolizumab (Keytruda) or dostarlizumab (Jemperli).
• Tumor mutational burden (TMB): TMB is a measure of the number of gene mutations (changes) inside the cancer cells. Breast cancer cells that have many gene mutations (a high TMB) might be more likely to be recognized as abnormal and attacked by the body’s immune system. If your breast cancer tissue is tested and found to have a high TMB (TMB-H), treatment with pembrolizumab (Keytruda) might be an option.
• NTRK gene changes: Some breast cancer cells might have changes in one of the NTRK genes. These gene changes can sometimes lead to cancer growth. Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) are drugs that target the proteins made by the abnormal NTRK genes and might be options for people with advanced breast cancer.

Blood tests

Blood tests are not used to diagnose breast cancer, but they can help to get a sense of a person’s overall health. For example, they can be used to help determine if a person is healthy enough to have surgery or certain types of chemotherapy.

A complete blood count (CBC) looks at whether your blood has normal numbers of different types of blood cells. For example, it can show if you are anemic (have a low number of red blood cells), if you could have trouble with bleeding (due to a low number of blood platelets), or if you are at increased risk for infections (because of a low number of white blood cells). This test could be repeated regularly during treatment, as many cancer drugs can affect blood-forming cells of the bone marrow.

Blood chemistry tests can help find if some of your organs, such as the liver or kidneys are not working as well. For example, if cancer has spread to the bones, it might cause higher than normal levels of calcium and alkaline phosphatase. If breast cancer spreads to the liver, it can sometimes cause high levels of liver function tests, such as aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Breast cancer does not spread to the kidneys, but if your bloodwork shows your kidneys are not working well, certain chemo drugs, like cisplatin, might not be used.

Breast cancer cells sometimes make substances called tumor markers that can be found in the blood. For breast cancer that has spread to other organs, tumor markers that might be checked include carcinoembryonic antigen (CEA), cancer antigen 15-3 (CA 15-3), and cancer antigen 27-29 (CA 27-29). Blood tests for these tumor markers are not used by themselves to diagnose or follow breast cancer.