Breast cancer is classified into subtypes based on the characteristics of the tumor cells. HER2-positive breast cancer makes up about 15% to 20% of all cases. This classification is based on cancer cells producing abnormally high levels of the HER2 protein. The presence of this high protein level determines the treatment approach, often including targeted therapies.
Understanding HER2 Gene Amplification
The HER2 protein (Human Epidermal growth factor Receptor 2) is a receptor found on the surface of all breast cells. Its normal function is receiving signals that regulate cell growth, division, and repair. This signaling process is tightly controlled to ensure cells multiply only when necessary.
HER2-positive cancer develops when the HER2 gene malfunctions and makes too many copies of itself. This genetic error is called HER2 gene amplification. This amplification results in an excessive number of HER2 receptors on the tumor cell surface, known as protein overexpression. This overabundance causes the cell to receive constant growth signals, leading to the rapid, uncontrolled division that defines the cancer.
Acquired vs. Inherited Genetic Alterations
Determining if HER2-positive breast cancer is genetic requires understanding the difference between somatic and germline alterations. Somatic alterations are acquired during a person’s lifetime and confined to specific cells. Germline alterations are inherited and present in every cell of the body.
The HER2 gene amplification causing HER2-positive breast cancer is overwhelmingly a somatic alteration. This genetic change occurs only within the tumor cells themselves, developing spontaneously as the cancer forms. Since the alteration is confined to the tumor, it cannot be passed down from parent to child.
Therefore, the HER2-positive status itself is not an inherited condition. The abnormal copying of the HER2 gene is an acquired change happening only in the breast tissue. This means a person’s HER2 status does not predict the same status in their children or siblings.
Inherited Risk Factors and Genetic Testing
While HER2-positive status is not inherited, a person may still have an inherited genetic risk that predisposed them to developing breast cancer. These inherited risks are caused by germline mutations in other genes, which are present in every cell. For example, mutations in the BRCA1 and BRCA2 genes increase a person’s lifetime risk for breast cancer generally.
These inherited mutations are independent of the tumor’s HER2 status. A tumor in a person with a BRCA mutation can be HER2-positive or HER2-negative. Genetic testing and counseling are recommended if there is a strong family history of breast or other related cancers.
Genetic testing analyzes a blood or saliva sample to look for these inherited germline mutations. A genetic counselor helps patients understand their personal risk and whether they should pursue testing. This process clarifies the underlying inherited predisposition, which differs from the acquired genetic change within the tumor that makes it HER2-positive.
Determining HER2 Status in Tumor Tissue
To determine if a tumor is HER2-positive, a sample of the tumor tissue is analyzed after a biopsy or surgery. Testing is performed on all newly diagnosed invasive breast cancers because the result dictates treatment decisions.
The initial and most common test is Immunohistochemistry (IHC), which measures the amount of HER2 protein on the surface of the cancer cells. IHC results are scored from 0 to 3+. A 3+ score indicates HER2-positive status, while 0 or 1+ indicates HER2-negative status.
If the IHC result is ambiguous (scoring 2+), a second test is performed to confirm the status. This confirmatory test is usually Fluorescence In Situ Hybridization (FISH), which counts the number of copies of the HER2 gene inside the cell nucleus. The results guide doctors in selecting appropriate targeted therapies, which improve outcomes for patients with HER2-positive disease.