Early Stage Breast Cancer and Testing
- Breast cancer is the most commonly diagnosed cancer in women (excluding skin cancer) and the second leading cause of cancer death in women. When diagnosed with early-stage disease, it is important to understand the workup and testing performed so you can make informed decisions with your healthcare team regarding treatment.
- Several pieces of information are collected, including the stage of the breast cancer ( degree of local and distant spread), histology (looking at the cells under the microscope), and tumor marker testing to test for the presence in the cell of ER, PR, HER2, and Ki67.
- All of this information and individual factors, such as overall health, are used to guide treatment recommendations. The presence or absence of tumor markers (specifically ER and HER2) can provide even more options for targeted therapies for these markers.
- Early-stage breast cancer is treated with the goal of curing the disease and often involves surgery to remove the cancer. The therapy that comes before or after surgery includes chemotherapy, endocrine therapy, targeted HER2 treatment, and radiation.
- The combination and timing of these treatments can vary depending on where you are treated, your cancer type, and your overall health and age. It is important to have a thorough discussion with your healthcare team regarding potential treatment options personalized to you and your cancer.
Early-stage breast cancer refers to cancer that is typically smaller in size and confined to the breast and surrounding tissue. As is the case in most cancers, when the disease is caught in its earlier stages, there is a higher chance of cure.Read More
Workup and Diagnosis of Early Stage Breast CancerMost breast cancers, around 90%, are found on screening mammograms, while others are found on self-breast exams or clinical exams by a healthcare provider. If your screening mammogram or breast exam is abnormal and concerning for cancer, you will then be referred for more detailed imaging and workup as follows:
- Typically, a diagnostic mammogram (which is a more detailed mammogram) and a breast ultrasound are performed. The lymph nodes in the axilla (armpit) will be looked at as well
- An MRI may be performed to get additional information
- If the imaging is suspicious, a biopsy is performed of the concerning area in the breast and any suspicious lymph nodes in the axilla (armpit)
- The biopsy, if positive for cancer, is tested for several hormone receptor and protein markers, often referred to as “tumor markers”
- Based on all of the information gathered above, additional imaging may be performed to rule out the spread of distant or metastatic disease
After all of this information is gathered to provide a detailed picture of your breast cancer and stage the cancer. The staging of the cancer gives information about how large the breast mass is and if it has invaded surrounding tissue. Staging also tells us if the disease has spread to lymph nodes or to distant sites. The other hormone receptor and protein marker tests found in the biopsy tell us the cancer cells’ behavior and potential targeted therapies.
Your healthcare team will use several pieces of information, including your personal health and treatment goals, the stage of breast cancer, and information from the biopsy to come up with personalized treatment recommendations.
What Specific Testing is Performed on the Biopsy?
The main information gathered from the biopsy uses histology and tumor marker testing.
Histology is when the pathologist looks at the cancer cells under the microscope and looks for specific features to provide a grade from 1-3. Grade 1 (well-differentiated) cells are less aggressive, and Grade 3 (poorly differentiated) are more aggressive. Features used to create a grade include:
- rate of cell division (mitotic count)
- irregularity of the cell (nuclear grade)
- the arrangement of the cells in relation to each other
- gland formation
Other valuable information gathered from histology includes the general cell type as well as lymphovascular invasion (LVI). “Lymphovascular invasion, abbreviated LVI, is looking at the tumor under the microscope and seeing if the cancer cells are invading the nearby vasculature. And it gives a sense that this tumor may be more aggressive or have the likelihood to spread,” says Dr. Jessica Tao a medical oncologist at Johns Hopkins Kimmel Cancer Center specializing in breast cancer.
Tumor Marker or Pathologic Testing
Tumor marker testing looks for specific hormone receptors and proteins in the cell. The presence or absence of these markers is measured by a test called immunohistochemistry (IHC). This expression or levels of these tumor markers is usually reported as a percentage from 0-100%, with 100% meaning all cells express these molecules, while a low % or 0% would mean very few or none of the cells have the tested tumor marker.
Tumor marker testing gives us important information about the behavior of the cancer cells and potential targeted therapies that can be used to treat your cancer.
The testing performed in the initial workup of breast cancer can vary depending on where it is performed, but most tumor marker testing includes:
- Estrogen receptor (ER)
- Progesterone receptor (PR)
- Human epidermal growth factor receptor 2 (HER2)
In the case of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), the presence or absence tells us not only how the cancer will act but also what targeted therapies specific to the tumor markers are effective. Most targeted therapies that can be used in the treatment of early-stage breast cancer look specifically at estrogen receptor (ER) or HER2-positive cells.
Ki-67 tells us how fast the cells are dividing, with a higher percentage meaning the cells are dividing more quickly, and the cancer is typically more aggressive.
How Does This Information Guide Treatment Recommendations?
All of the information described above is analyzed and used by your healthcare team to guide treatment recommendations. To summarize, the information used includes:
- The stage of breast cancer – the extent of the disease and where it has spread
- The histology – cells observed under the microscope and their behavior
- Tumor marker testing – the presence or absence of specific hormone receptors or proteins on the cancer cells
- Patient-specific factors – overall health, age, goals of treatment
While all of this information guides general recommendations for treatment, tumor marker testing (presence of ER, PR, HER2) provides options for targeted therapies specific to these markers.
The most common type of breast cancer is ER-positive, HER2-negative, representing approximately 60-70% of diagnosed breast cancers. When cells do not have an ER, PR, or Her2 present, it is called triple-negative breast cancer, representing around 15% of cases. HER2-positive breast cancer (which can be ER or PR-positive) represents another 15 – 20% of cases.
Each of these different breast cancer types has different recommendations for targeted therapies. All patients with early-stage breast cancer will typically undergo surgery to remove the cancer. There is often recommended treatment before or after surgery, which can include various combinations of chemotherapy, endocrine therapy targeting the estrogen receptor, Her2 targeted therapy, and radiation. The treatment offered before or after surgery can also depend on the type of surgery you receive (lumpectomy or a mastectomy).
The potential treatment options are varied and difficult to interpret. Decisions regarding treatment for your early-stage breast cancer should be thoroughly discussed with your healthcare team. The important thing to recognize is that a lot of information is gathered and considered to make the best and most personalized treatment recommendations.
If you have questions about the workup and testing performed on your breast cancer or feel you did not receive a complete workup and testing, please consult with your healthcare team.
Are There Other Questions I Should Ask or Testing I Can Consider?
Should I consider additional molecular profiling with next-generation sequencing for my early-stage breast cancer?
Next-generation sequencing looking for mutations in the cancer tissue is typically reserved for advanced or metastatic breast cancer. “Molecular profiling at this juncture is probably less relevant, meaning next-generation sequencing,” according to Dr. Tao.
Is my family at risk of developing cancer as well?
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; not everyone is recommended to undergo additional testing. Specific factors in your personal or family history that might make you a candidate for further testing include but are not limited to:
- Personal diagnosis of breast cancer <50 years old
- Personal diagnosis of triple-negative breast cancer, multiple separate breast cancers
- Personal or family history of male breast cancer
- Personal diagnosis of breast cancer with Ashkenazi Jewish Ancestry
- Family history of breast cancer diagnosed <50 years old
- Family history of ovarian or pancreatic cancer or prostate cancer with metastatic or high-risk staging
- Family history of multiple breast or prostate cancers
If you believe you might be a candidate for further testing, please discuss further with your healthcare team.
What additional testing can I undergo to see if I have an inherited cancer-causing gene?
Additional testing looks for specific inherited cancer-causing genes or germline mutations, such as BRCA 1 and BRCA 2. This testing can be done at your convenience and typically requires a saliva or blood sample.
If I qualify for germline testing, why should I get it?
If negative, it gives the family peace of mind. If positive, it can potentially guide future treatments for your cancer. It can also allow families to test and protect themselves by undergoing early and more regular screening if the results are positive.
Are there any ongoing clinic trials available?
Multiple ongoing clinical trials for early-stage breast cancer vary widely based on your disease and where you are receiving treatment. Please ask your healthcare team about available options if you are interested.