Breast Cancer - Questions to Ask About Testing
- Testing in breast cancer helps to characterize the behavior of the cancer, the spread of disease, and targets for treatment. All of this information is used together along with individual factors to guide treatment.
- Mammogram is used for screening and is the most common way early breast cancer is diagnosed. Following a suspicious mammogram, additional imaging often with breast ultrasound and occasionally a breast MRI are used. Biopsy is also performed for suspicious masses.
- Based on mammogram, ultrasound, +/- breast MRI, clinical exam, patient history, and lab tests, additional imaging may be performed to rule out metastatic disease.
- Biopsy looks at the grade of the cancer and presence of certain hormone receptors and proteins (ER, PR, HER, Ki67). These hormone receptors and proteins are often referred to as “markers” or “tumor markers” .
- All of this testing is performed in early stage and advanced breast cancer to guide treatment. Early stage breast cancer typically involves surgery with treatment before or after based on information gathered to help with cure. Advanced disease does not typically focus on surgery and uses medications to treat the cancer.
- Advanced breast cancer utilizes next-generation sequencing (NGS) in addition to other tests to help determine additional targeted therapies.
- Testing for hereditary cancers is also performed if diagnosed with metastatic disease or if there is a strong personal or family history concerning inherited DNA mutations that can cause cancer.
- If you have additional questions, do not hesitate to contact your healthcare team to discuss further.
Depending on the specific features of your breast cancer as well as other details, including your personal and family history, there are specific guidelines for the workup and testing of your breast cancer which help to further guide and personalize treatment.Read More
What is the first type of testing typically done to identify breast cancer?A mammogram uses X-ray imaging to screen for and diagnose breast cancer in earlier stages when it is confined to the breast or lymph nodes in the armpit. It is recommended that all women undergo yearly mammograms starting at 40 years old. If you are at higher risk for breast cancer based on personal or family history, you may need to undergo screening earlier.
What if a lump or breast mass is found during a physical exam?
Most early-stage breast cancers are identified on screening mammograms. If you have a breast mass found on exam, you will be referred for a mammogram in most cases.
What happens if the mammogram is abnormal or suspicious?
Specific criteria are used by radiologists to determine what breast masses are concerning and need additional workup or can be watched. If a mammogram is suspicious, additional imaging will be performed, often with a breast ultrasound and sometimes a breast MRI. A biopsy of the suspicious breast mass and any abnormal lymph nodes will also be performed.
I had breast imaging and a biopsy. What tests do they run on the biopsy?
With the breast biopsy, the pathologist uses histology and protein and hormone receptor testing to gather more information. Histology looks at the cell’s general structure under the microscope and tells us if the tissue is actually cancer. In addition, it tells us what type of cancer is present as well as the grade of the cancer. Grade 1 (well differentiated) is less aggressive, and Grade 3 (poorly differentiated) is the most aggressive. Lymphovascular invasion (LVI) is also noted to see if the cancer cells are invading the nearby vascular system.
Hormone receptor and protein testing look for what your physician will likely refer to as “markers” or “tumor markers” in the cell. The is measured by a test called immunohistochemistry (IHC), which identifies the presence or absence of these markers in your cancer cells. This is usually reported as a percentage from 0-100%, with 100% meaning all cells express these markers, while a low percentage or 0% means very few or none of the cells have the tested molecule.
The markers tested for include:
- Estrogen Receptor (ER)
- Progesterone Receptor (PR)
- Human epidermal growth factor receptor 2 (HER2)
Is there any other testing that is performed?
Information gathered from the clinical exam and history, breast imaging, biopsy, and abnormal lab tests is used to determine the need for additional imaging to rule out metastatic disease. These tests usually include a CT of the chest, abdomen, and pelvis with a bone scan or a PET scan. Sometimes, an MRI of the brain can be performed, as well.
What is done with all these test results?
The imaging, clinical exam, and biopsy help to determine the stage of the breast cancer, the specific subtype of breast cancer, and its expected behavior or aggressiveness. These results from testing are then used in combination with other factors such as your personal history, age, overall health, and treatment goals to guide treatment recommendations.
What is breast cancer staging?
The stage of a cancer determines the extent of local disease, the lymph node involvement, and if there is a distant spread or metastatic disease. The specific staging can vary between types of cancers. In breast cancer, the treatment for different stages of disease can vary significantly. Again, clinical exams and imaging are used to determine the stage.
What is the breast cancer subtype?
The result from the biopsy tells us the general type of cancer, which can be determined by looking at the cell. However, additional testing of markers (ER, PR, HER2) gives us more specific information. Patients with ER or PR present are often called hormone receptor-positive breast cancer, while the presence of HER2 (regardless of ER or PR) makes it a HER2-positive breast cancer. The absence of any of these markers makes it triple-negative breast cancer.
The most common type of breast cancer is ER-positive, HER2-negative, representing approximately 60-70% of diagnosed breast cancers. Triple-negative breast cancer represents around 15% of cases. HER2-positive breast cancer represents another 15 – 20% of cases.
Why are staging and breast cancer subtypes important?
This information is used with other factors such as your personal history, age, overall health, and treatment goals to guide treatment recommendations.
Staging determines if a patient has early-stage or advanced breast cancer. The treatment recommendations vary significantly with different stages of breast cancer. Often in early stage or localized, breast cancer treatment will consist of surgery to remove the cancer. The treatment done before or after surgery can vary significantly based on individual factors and traits specific to the cancer and can include chemotherapy, radiation, hormone therapy, and targeted HER2 therapy, to name a few. With the advanced stage, the treatment is more focused on medical therapies. According to Dr. Tao, “In metastatic breast cancer, generally surgery to remove the primary tumor is not utilized.”
The breast cancer subtype and grade determined from the biopsy testing tell the healthcare team how the cancer will likely act and respond to treatment. Additionally, when looking at estrogen receptors and HER2, it can provide additional treatment options for patients. Therapies for the estrogen receptor can target the receptor itself or the production of estrogen, which interacts with the receptors to stimulate the cancer cell. There are also many targeted treatments for HER2 that can be used when HER2 is present in the cells.
You mentioned early-stage and advanced breast cancer. Is the testing different?
Thanks to screening efforts, most patients diagnosed with breast cancer present with early-stage breast cancer. Additionally, most patients who present with advanced or metastatic disease have had a prior diagnosis and treatment of early-stage breast cancer. In the uncommon situation where you present with a diagnosis of metastatic disease and no prior history of breast cancer, much of the testing workup, which helps guide future therapies, is the same as early-stage disease.
If there is a prior history of breast cancer, a new biopsy is often obtained and compared to the old biopsy from the prior breast cancer. If a cancer recurs or spreads distantly, the expression of these markers (ER, PR, HER2) often remains the same. If there is a difference in these receptors, it can mean there is a new primary disease or separate breast cancer that developed, which is separate and unrelated to the prior breast cancer. This can change treatment significantly if it is thought to be a new breast cancer versus a recurrence of a prior disease.
Advanced-stage breast cancer has many of the same tests performed as early-stage cancer. The additional testing that should be performed with advanced disease is next-generation sequencing.
What is next-generation sequencing?
Next-generation sequencing (NGS), typically done via a tissue biopsy, analyzes multiple portions of the tumor DNA to identify other potential markers or DNA mutations that can be targeted for treatment. Next-generation sequencing can be done via tissue biopsy, which tests a piece of the tumor, but if there is a need for a repeat biopsy and an additional biopsy procedure is unfeasible, NGS can also be performed with a liquid biopsy.
Why is next-generation sequencing used?
Typically, when a patient presents with a diagnosis of advanced breast cancer, multiple therapy options are determined based on the subtype of breast cancer (hormone positive, HER2 positive, triple negative). “Next-generation sequencing doesn’t always affect the first-line treatment, meaning what medications you get right away. Sometimes patients are started on first-line treatment first and then at progression, meaning when the treatment stops working and there are new tumors or growing tumors, then your oncologist might recommend a biopsy of a growing site,” says Dr. Tao.
Testing with NGS can also help with enrollment in ongoing clinical trials.
What is a liquid biopsy?
A liquid biopsy collects a sample of your blood and analyzes pieces of cancer cells that are in the bloodstream called circulating tumor DNA, or ctDNA. This can then be tested using NGS to determine targetable mutations.
Why use a liquid biopsy?
Tissue biopsy is the gold standard for biopsy and testing for NGS. However, if tissue biopsy is unfeasible and repeated NGS is needed to test for ongoing changes in the cancer, DNA liquid biopsy can be a less invasive and repeatable alternative to tissue biopsy.
Is there any other testing that can be done?
Testing the tumor for DNA mutations with NGS is done in metastatic disease. These tumor DNA mutations are specific to the cancer itself and not present in other cells in your body. This is called somatic testing or tumor-based testing. You can also test for inherited DNA mutations that can be passed down from generation to generation, which increases your risk of specific cancers based on the inherited DNA mutation. This is known as germline testing.
When should I undergo germline (hereditary cancer) testing?
Depending on your personal and family history, you might be at risk for having a germline mutation or an inherited mutation in your DNA that increases your risk of certain cancers. Breast cancer is the most common cancer among women, and not everyone has a clear risk or is recommended to undergo additional testing.
You should undergo testing if you have:
- A personal history of metastatic breast cancer
- A personal diagnosis of breast cancer <50 years old
- A personal diagnosis of triple-negative breast cancer, multiple separate breast cancers
- A personal or family history of male breast cancer
- A personal diagnosis of breast cancer with Ashkenazi Jewish Ancestry
- A family history of breast cancer diagnosed <50 years old
- A family history of ovarian or pancreatic cancer or prostate cancer with metastatic or high-risk staging
- A family history of multiple breast of prostate cancers
Any other questions I should be asking?
How much are these tests going to cost me?
Costs can vary based on your insurance provider and the test obtained. Please discuss further with your healthcare team.
What should I expect to go through with each test?
Biopsy of the breast or metastatic site is a procedure that can cause pain and discomfort. Other tests are typically non-invasive or sometimes require a blood sample.
What clinical trials are available?
Clinical trial availability will vary based on your specific disease and the site where you are receiving treatment. NGS testing can help determine if a clinical trial is available for you.