Molecular Testing for Breast Cancer

What is molecular testing?

If you are having molecular testing done, your tumor is being tested for biomarkers. Biomarkers (also called biological markers) are molecules that can be found in tumor tissue. When breast cancer is diagnosed, your provider will want to test for biomarkers. Knowing about your biomarkers helps your provider understand what is happening in your cells. This information is then used to help guide your treatment options and helps you and your provider customize your treatment plan, also called “personalized medicine.” The results of your molecular testing will be given to you in a pathology report. Ask your provider any questions you have about this report.

What are molecular tests used for breast cancer?

Hormone Receptor Status (estrogen and progesterone)

This test tells us if the tumor has extra estrogen and/or progesterone receptors. One or both receptors may be positive. A positive result is called ER+/PR+ (estrogen receptor positive/progesterone receptor positive). The result you see depends on the test. There is no standard for reporting the receptor status, so you may see any of these:

• A percentage of the cells that tested positive for receptors (from 0% to 100%).
• A number between 0 and 3, with 0 being no receptors and 3 being the most receptors.
• An Allred score is a combination of the percent positive and their intensity. The score is from 0-9, with 9 being the most strongly receptor-positive.
• Positive or negative.

ER+ and/or PR+ tumors may be treated with hormone therapy, which works by blocking the tumor cells from getting the estrogen and progesterone they need to grow.

HER2/neu Status

HER2/neu (human epidermal growth factor receptor 2) is a protein that is found on the surface of some breast cancer cells. There are two tests for HER2: the immunohistochemistry (IHC) test and the FISH test (fluorescent in situ hybridization). The results of these 2 tests are shown differently in your pathology report and can look like:

• IHC test looks for overexpression (more HER2 receptors than normal). The result is reported as a number from 0 to 3+.
  • HER2 negative can be either 0 or 1+.
  • HER2 positive can be either 2+ (borderline) or 3+.
  • If you have a 2+ (borderline) result, you will likely have a FISH test done to check if it is positive or negative.
• FISH test checks the tumor for extra copies of the HER2 gene. The result is reported as positive or negative.

Tumors that are HER2 positive might be treated with targeted therapy.

PIK3CA Mutation Test

If your tumor is hormone receptor positive and HER2 negative, you might have PIK3CA (phosphatidylinositol 3-kinase) testing done. There are certain medications that target this mutation that might be added to your treatment plan based on your test result.

OncoType Dx Test 

OncoType Dx test looks at the activity of 21 genes found in tumor cells. It uses this information to predict the risk of recurrence (the cancer coming back after treatment), how likely you are to benefit from chemotherapy treatment after surgery in early-stage cancer, and how radiation therapy may help after DCIS (ductal carcinoma in situ, or noninvasive cancer) surgery.

This test may be used for DCIS or stage I (1) or II (2) invasive breast cancers that are ER+ (estrogen receptor positive) and have not spread to the lymph nodes.

The result is reported as a "Recurrence Score," which is a number from 0 to 100 that shows a low, intermediate (medium), or high risk of recurrence. This score can be used along with other tumor tests to choose the best treatment for you.

MammaPrint Test

This tests the activity of 70 genes found in tumor cells to predict the risk of recurrence (the risk of the cancer coming back after treatment). This test may be used for stage I (1) and II (2) breast cancers that are smaller than 5 cm (centimeters) and that have not spread to the lymph nodes. The results are reported as either low risk or high risk. The result of this test, and other traits of the tumor, may be used to guide your treatment.

Urokinase Plasminogen Activator (uPA) and Plasminogen Activator Inhibitor (PAI-1) Tests

Higher levels of these biomarkers in the tumor tissue may mean that the tumor is more aggressive (grows faster). These tests may be used to predict prognosis in early-stage breast cancers that have not spread to the lymph nodes. A very good prognosis may mean that you do not need chemotherapy treatment.

Prosigna (PAM50) Breast Cancer Prognostic Gene Signature Assay

This is a genomic test that looks at 58 genes to find the risk of recurrence of hormone-receptor positive (ER+/PR+) breast cancer. The results are reported as a risk of recurrence score from 0 to 100 in 2 ways:

• Node-negative (no cancer in lymph nodes) cancers are either low (0-40), intermediate (41-60), or high (61-100).
• Node-positive (cancer in lymph nodes) cancers are classified as low (0-40) or high (41-100).

Knowing if you have a high or low risk of distant recurrence more than 5 years after diagnosis can help decide whether 5 or 10 years of hormonal therapy is best for your treatment.

Planning Your Breast Cancer Treatment 

There are many different tests used to learn about a breast cancer tumor. The tests that are ordered for you depend on your specific cancer. These tests and results can help guide your treatment. Ask your provider which tests are right for you.