HER2-positive breast cancer: testing, results and targeted treatment

Breast cancers are described by features of the cells as well as by size and spread. One of these features is the amount of HER2 on the cell surface. Breast Cancer Now explains that the protein stimulates cells to grow, so a cancer with high levels of HER2 is called HER2-positive, and one with normal levels is called HER2-negative.

Being HER2-positive describes the tumour biology, not how advanced the cancer is. It is separate from the stage, and from whether the cancer is also sensitive to oestrogen, which is why a pathology report usually lists several results together.

Cancer Research UK uses the related term triple negative for cancers that have no receptors for oestrogen, progesterone or HER2. Those cancers are a different group, and HER2-targeted drugs are not part of their treatment.

HER2-positive disease does not look or feel different from other breast cancer from the outside, and HER2 status is found only on laboratory testing. The symptoms are those of breast cancer in general. The NHS lists a lump or swelling in the breast, chest or armpit, changes to the skin such as dimpling, a change in size or shape, nipple discharge, an inverted nipple and a rash on the nipple.

The NHS says breast pain alone is not usually a symptom of breast cancer, that many lumps are caused by other conditions, and that you should see a GP about any lump or change that is not normal for you. If your symptoms could be due to cancer, a GP may refer you to a specialist breast clinic for tests.

Breast Cancer Now says the test is done in a hospital laboratory on a sample of cancer tissue removed at biopsy or surgery. The usual first test is immunohistochemistry (IHC), a staining process, and it is reported as a score from 0 to 3+.

Where the IHC score is borderline at 2+, the sample should be retested using more specialised techniques, which give a final answer of HER2-positive, HER2-low or HER2-negative. Results are usually available within 1 to 3 weeks, so some waiting is normal.

Ductal carcinoma in situ (DCIS) is not routinely tested for HER2. If a pathology report does include a HER2 result for DCIS, Breast Cancer Now says it will not change treatment options, because targeted therapies such as trastuzumab are not used for DCIS.

A newer category is HER2-low. Breast Cancer Now says there is evidence that HER2-low breast cancer may benefit from HER2-targeted therapy, and that the drug trastuzumab deruxtecan can be used for HER2-low cancers in some instances.

If the cancer is HER2-negative, targeted therapies aimed at HER2 will not help. Treatment is then planned around other features, and Breast Cancer Now lists surgery, chemotherapy, radiotherapy, hormone therapy and bisphosphonates as the options, depending on the characteristics of the cancer and your general health.

The NHS says treatment for breast cancer depends on the size and type, where it is, whether it has spread and general health. The main treatment is usually surgery, with chemotherapy, radiotherapy, hormone therapy, and targeted medicines and immunotherapy as other common treatments. Surgery can mean breast-conserving surgery, mastectomy, or removal of armpit lymph nodes.

For HER2-positive disease, Breast Cancer Now says you will usually be offered a targeted therapy alongside or after chemotherapy. The most commonly used is trastuzumab (Herceptin). Other drugs it lists for HER2-positive cancer are pertuzumab with trastuzumab (Phesgo), trastuzumab emtansine (Kadcyla), trastuzumab deruxtecan (Enhertu), neratinib (Nerlynx) and tucatinib (Tukysa). Which one applies depends on your own situation, and these are prescription-only medicines decided by your cancer team.

Breast Cancer Now says targeted therapy can be given to shrink a larger cancer before it is removed by surgery, to reduce the chance of breast cancer coming back after surgery, or when cancer has come back or spread. Targeted therapies block processes in the cells that help cancer grow, and side effects depend on the drug, with extra effects possible if it is combined with chemotherapy.

The NHS says you will have regular check-ups during and after treatment, and may have tests and scans. If you have symptoms or side effects you are worried about, you do not need to wait for your next check-up.

If breast cancer spreads it is called secondary breast cancer, and the NHS says it most commonly affects the bones, liver, lungs or brain. For advanced disease, the NHS says treatment aims to slow the spread, ease symptoms and help people live longer, and many people can live a normal life for a number of years.

Your clinical nurse specialist is a good first contact for questions. Charities such as Breast Cancer Now run helplines staffed by specialist nurses.