Triple Negative Breast Cancer
Biomarkers and Genetic Testing
One of the first steps to determining whether your breast cancer is triple negative is through biomarker testing. This testing is performed on a biopsy sample or metastatic site in a laboratory by a pathologist, a physician who has special training in identifying diseases by studying cells and tissues under a microscope. The goal is to identify the molecular characteristics of the cancer and determine what personalized treatment options you may be offered, such as targeted therapy or immunotherapy.
A crucial piece of information needed to develop a breast cancer treatment plan is your estrogen receptor, progesterone receptor, as well as your human epidermal growth factor receptor 2 status. It is important to understand that TNBC diagnosis, is a diagnosis of exclusion, meaning other types of breast cancer are ruled out.
The Three Main Biomarkers
TNBC is defined as being estrogen receptor negative (ER-), progesterone receptor negative (PR-) and human epidermal growth factor receptor-2 negative (HER2-), meaning these hormones and HER2 are not driving the cancer’s growth.
The estrogen receptor (ER) is stimulated by estrogen and provides rapid growth signals. ER status can be positive or negative.
- ER- (negative) breast cancer does not need estrogen to grow. This means that the cancer will keep growing when estrogen is not present and will not stop growing when treated with substances that block estrogen from binding.
The progesterone receptor (PR) binds progesterone and provides rapid growth signals. The PR status can be positive or negative.
- PR- (negative) breast cancer does not need progesterone to grow. This means that the cancer will keep growing when progesterone is not present and will not stop growing when treated with substances that block progesterone from binding.
The human epidermal growth factor receptor-2 (HER2) is a protein involved in normal cell growth and is found on the surface of all cells. It is also referred to as HER2/neu. The HER2 status can be positive or negative. In normal cells, HER2 helps control cell growth. Some breast cancers have too many HER2 genes within the cell or HER2 receptors on the outside of the cell.
- HER2- breast cancer cells do not have an excess of the HER2 receptor.
- HER2-low breast cancer is a new classification of this breast cancer biomarker in which the cancer cells have a slightly higher amount than normal of HER2 on their surface and do not have more than two copies of the HER2 gene. HER2-low breast cancer has usually been treated like HER2-negative breast cancer because the cancer cells do not make enough HER2 protein for drugs that target HER2 to work. However, newer drugs that target HER2 have been shown to be effective in treating HER2-low breast cancer.
Genetic Testing
Some breast cancers are passed down through families. This is known as hereditary cancer. Depending on your family history or other features of your cancer, you may be referred for genetic testing and counseling to find out if yours is hereditary. The testing is used to determine whether a person was born with or inherited abnormalities in DNA or cells that can cause breast cancer. The most well-known genetic abnormalities are the breast cancer 1 and 2 genes (BRCA1 and BRCA2). Mutations in the BRCA1 and BRCA2 genes can increase the risk of developing breast and ovarian cancers.
Researchers have discovered that TNBC occurs in many women who have BRCA1 mutations and in a few with BRCA2 mutations. Knowing you have a specific genetic mutation may help your health care provider choose the best treatment option for you. This information may also be useful to family members who can then decide to undergo genetic testing themselves.
Genetic testing may be performed before cancer diagnosis based on family history or after receiving a cancer diagnosis. The testing will determine whether you carry an abnormality in the corresponding risk gene. Some characteristics suggestive of hereditary cancer include the following:
- Family history of cancer, cancer at an early age, rare or multiple cancers in one relative
- Particular patterns of cancer, such as breast and ovarian cancers in the same family, or even pancreatic cancer, melanoma and early age prostate cancer.
- A family member who has had genetic testing revealing a mutation
In most cases, genetic tests are ordered by a doctor or other health care provider. Doctors send these tests to laboratories that are regulated under the Clinical Laboratory Improvement Amendments (CLIA) program to meet standards for accuracy and reliability.
Having one or more abnormal genes is not necessarily the cause of your breast cancer. It does, however, offer valuable information that you can discuss with your health care provider. Together, you can explore ways to lower future risk for your family members, which may include frequent screenings, medication and, in some cases, preventive surgery.
If genetic testing is recommended, ask for a referral to a genetic counselor, either on staff or elsewhere. The genetic counselor (or advanced practice nurse with genetics training) will discuss your medical history and cancer screening history, your family’s cancer history, the benefits and limitations of genetic testing, and current laws regarding the privacy of genetic information.
It is important to know your medical family history on both sides of your family — mother and father. For example, a father can carry a breast cancer gene mutation and never personally get breast cancer; however, 50 percent of his offspring will carry the gene mutation passed on to them by his DNA.
Words to Know
Biomarker testing: A test performed on a sample of tissue, blood or other body fluid to check for certain genes, proteins or other molecules that may be a sign of cancer.
Genetic testing: A laboratory test that looks for inherited changes in a person’s genes that may indicate an increased risk of developing a specific disease or condition or of having a child or other family member with the disease or condition. This type of genetic testing is called germline testing.
Hereditary cancer: This inherited disorder is caused by mutations (changes) in certain genes passed from parents to children. Consider having genetic testing to confirm.
