What HER2 is
HER2 is a protein on the cell surface that works as a growth antenna. It is best known from breast cancer, but it also appears in other tumours. In colorectal cancer, 3-5 % of cases have the HER2 gene amplified (too many copies) or the protein overexpressed. It is more common in RAS and BRAF wild-type tumours (without a mutation) and in the left colon and rectum; among RAS wild-type tumours the figure rises to 5-8 %.
It is not hereditary: it is an alteration acquired by the tumour.
How it is determined
- Immunohistochemistry (IHC): stains the protein in the tumour tissue and gives a score from 0 to 3+. A 3+ result is considered positive.
- FISH / ISH: counts the gene copies. It is used to confirm 2+ (borderline) cases.
- NGS panel: detects the amplification together with the other alterations (RAS, BRAF, MSI…). This is now the most common route in hospitals running broad panels.
European and American guidelines recommend testing HER2 in every patient with RAS wild-type metastatic disease. If your molecular report does not mention it, ask.
Why it changes treatment
- Anti-EGFR antibodies (cetuximab, panitumumab) work less well when HER2 is amplified, even if the tumour is RAS wild-type. That is why it is worth knowing before starting.
- There are HER2-targeted therapies that have shown responses in patients who had already received chemotherapy.
HER2-targeted treatments
| Combination | What it is | Evidence |
|---|---|---|
| Trastuzumab + tucatinib | Intravenous antibody + tablet | MOUNTAINEER study: responses in close to 40 % of previously treated RAS wild-type patients, with long durations. Approved in the United States (2023); access in Europe varies. |
| Trastuzumab deruxtecan (T-DXd) | Antibody linked to a chemotherapy that is released inside the cell | DESTINY-CRC01 study: responses around 45 % in IHC 3+ tumours. Risk of pneumonitis (lung inflammation), which means watching for cough or breathlessness and reporting it immediately. |
| Trastuzumab + pertuzumab or + lapatinib | Two antibodies, or antibody + tablet | Phase II studies (MyPathway, HERACLES) with responses around 30 %. These are the older combinations. |
These are treatments without classic chemotherapy (apart from the payload carried by T-DXd), with different side effects: diarrhoea and skin problems (tucatinib), nausea and low blood counts (T-DXd), and heart monitoring (echocardiogram) with all of them.
Access in Spain
None of these combinations yet has a broad funded indication for colon cancer in Spain; the usual route is a clinical trial, an access programme or an individual request by the hospital. If your tumour is HER2-positive, ask your team to look for open trials (our guided trial finder lets you filter by HER2) and to consider referral to a centre with active studies.
What to ask at your appointment
- Has HER2 been tested in my tumour? By IHC, FISH or NGS, and what was the result?
- Am I RAS and BRAF wild-type? Does that change the plan if HER2 is amplified?
- Is there any trial with anti-HER2 drugs I could join, here or at another hospital?
- If an anti-EGFR is proposed, has HER2 been taken into account?
- What heart and lung monitoring would I need with these drugs?
