What is HER2 and why does it cause cancer?
HER2, whose full name is human epidermal growth factor receptor-2, is also called ErbB2 and EGFR2, and belongs to the ErbB gene family. This gene family has three other brothers: EGFR1, which is associated with lung cancer, and EGFR3 and EGFR4.
These genes by themselves are harmless, like when you get a cut on your hand, and they work to repair the broken skin. But once HER2 is amplified or overexpressed, when it binds to a ligand, it is like a battery with positive and negative terminals connected, and some pathways mediated by HER2 protein are activated as if by electricity, and it “goes bad”, causing the body’s senescent cells to die on time, while a large number of new cells do not function accordingly, leading to cancer. The result is the development of cancer.
How the HER2 gene relates to breast cancer
- Amplification/overexpression of the HER2 gene may be present in tumors such as breast, ovarian, endometrial, gastric, and prostate cancers, with 20-30% of primary invasive breast cancers having HER2 gene amplification/overexpression.
- HER2 is an important molecular biological marker for breast cancer, and patients with HER2 overexpression have a poor prognosis, so patients with breast cancer need to be promptly screened for HER2 genes to clarify their situation.
How do breast cancer patients know if they are HER2-positive?
HER2 can be detected by biopsy pathology and is considered HER2 positive if any of the following are present in the pathology report:
- Immunohistochemistry: HER2: ++++ (strong positive);
- Molecular pathology: HER2 in situ hybridization dual-probe assay results with HER2/CEP17 ratio ≥ 2.0 and mean HER2 copy number/cell ≥ 6.0 indicate gene amplification, defined as positive.
What are the targeted agents for anti-HER2 therapy in breast cancer?
Once the test is clear for HER2, what are the target drugs?
Once a positive HER2 test is confirmed, patients need standard anti-HER2 therapy. “The first step in the process is to take the first step in the chain of action, thus “punishing the black and eliminating the evil and fighting crime”.
The mechanisms of action of the various HER2-targeting drugs are different, and so are the “links to disrupt”. The first of these is trastuzumab, a pioneer in the fight against HER2. Since 1998, when the FDA approved Trastuzumab, known as Herceptin, for the treatment of HER2-positive breast cancer, it has opened the door to anti-HER2 therapy for breast cancer, and new drugs have been introduced one after another. The currently available HER2-targeted drugs are detailed in the table below:
How is the choice of combination therapy for HER2 receptor positive expression in breast cancer?
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