HER2-Positive Breast Cancer: Causes, Diagnosis
Learn about HER2-positive breast cancer, including causes, symptoms, diagnosis using IHC and FISH.
HER2-Positive Breast Cancer
HER2-positive breast cancer is characterized by overexpression or amplification of the human epidermal growth factor receptor 2 (HER2/ERBB2) and typically lacks estrogen and progesterone receptor expression.
HER2-positive breast cancer is a fast-growing subtype of breast cancer. It accounts for approximately 10–15% of all breast cancers.
Additionally, HER2-enriched tumors frequently exhibit a high mutational rate associated with the activity of the APOBEC3B enzyme. APOBEC3B belongs to a family of cytidine deaminases that induce cytosine-to-uracil alterations in DNA, leading to clusters of mutations that contribute to tumor initiation and progression.
Unlike luminal or basal-like breast cancers, HER2-enriched tumors are primarily driven by genes involved in rapid cell proliferation and signaling pathways, including ERBB2 (HER2) and GRB7.
Clinically, HER2-enriched breast cancers tend to grow more rapidly and display more aggressive behavior than luminal breast tumors. Prior to the introduction of HER2-targeted therapies such as trastuzumab, this subtype was associated with a poor prognosis; however, targeted treatments have significantly improved patient outcomes.
Related Article: Triple-Negative Breast Cancer
What is the HER2 protein?
In normal breast cells, the HER2 protein plays a role in regulating cell growth and repair. In cancerous cells, the HER2 gene no longer functions normally, leading to uncontrolled cell proliferation and tumor formation.
These cancer cells contain multiple copies of the HER2 gene. Either the HER2 gene is amplified or it overexpresses HER2 receptors on the cell surface—or both. HER2 gene amplification and/or protein overexpression drive breast cancer development.
An excess amount of HER2 gene copies or HER2 protein causes cancer cells to divide more rapidly and behave more aggressively.
HER2-enriched breast cancers grow faster than luminal breast cancers and historically had the poorest prognosis among breast cancer subtypes before the introduction of HER2-targeted therapies.
HER2- enriched and HER2 – positive are different
HER2-positive and HER2-enriched breast cancers are related but not identical terms.
HER2-positive breast cancer
HER2-positive breast cancer is a determined by laboratory tests such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
HER2-positive tumors show overexpression of the HER2 protein or amplification of the HER2 gene. This excess HER2 signaling leads to aggressive tumor growth and makes these cancers responsive to HER2-targeted therapies such as trastuzumab.
HER2-enriched breast cancer
In contrast, HER2-enriched breast cancer is a molecular subtype identified through gene-expression profiling, such as PAM50 testing.
It is characterized by high expression of HER2-related genes and low expression of estrogen and progesterone receptor genes.
Most tumors classified as HER2-enriched show high HER2 activity, so they usually test HER2-positive in clinical tests. However, HER2-positive breast cancer is a broader category. Some HER2-positive tumors also express estrogen or progesterone receptors and therefore behave like luminal subtypes, not HER2-enriched ones.
Symptoms and Causes
HER2-positive breast cancer has symptoms similar to those of other breast cancer subtypes.
Related Article: Luminal Breast Cancer
What are the risk factors?
The risk factors for HER2-positive breast cancer are similar to those of other breast cancer subtypes.
Diagnosis and Tests
Diagnosis of HER2-positive breast cancer involves testing tumor tissue using immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
Treatment typically includes a combination of chemotherapy and HER2-targeted antibodies, along with surgery and, in some cases, radiation therapy. Treatment plans are tailored based on whether the disease is early-stage or metastatic.
- Testing: All invasive breast cancers are routinely tested for HER2 status.
- Tests used: Immunohistochemistry (IHC) assesses HER2 protein expression (a score of 3+ is considered positive), while fluorescence in situ hybridization (FISH) detects HER2 gene amplification.
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