HER2 positive breast cancer
Breast tissue sampled by a biopsy or after surgery is sent to a pathologist who will report on several features in the sample, including the status of molecular markers such as the estrogen receptor, progesterone receptor and HER2 (human epithelial growth factor receptor 2). These results will help a treating clinician determine the best treatments, which may include hormonal or targeted drugs. Around 15-20% of all breast cancer cases are HER2 positive, meaning that the breast cancer cells produce excessive amounts of the HER2 protein, which promotes the growth of this type of breast cancer.
In non-cancerous cells, HER2 is responsible for normal cell growth as well as other essential cellular processes, whereas excessive levels of HER2 in cancer cells leads to fast growing tumours.
Around one in five women with breast cancer have HER2 positive breast cancer, which can be more aggressive than some HER2 negative breast cancers. HER2 positive breast cancer may be hormone receptor positive (meaning it needs hormones oestrogen and/or progesterone to grow and reproduce) or hormone receptor negative. This can affect the treatment chosen. HER2 positive cancers tend to spread faster than other breast cancers but are much more likely to respond to treatment with drugs that specifically target HER2 receptors. Since most HER2 positive tumours can be successfully targeted, HER2 is no longer a marker for a poor prognosis.
Symptoms of HER2 positive breast cancer
There are no specific HER2 breast cancer symptoms, but HER2 breast tumours share similar symptoms with other breast cancer types. However, it is important to remember that many people show no symptoms when breast cancer is first diagnosed, which is why breast awareness and attending regular mammograms after age 50 is essential.
For all breast cancers, including HER2 positive breast cancer, symptoms may include:
- New lump/s or thickening in the breast, especially if only in one breast
- Changes in the shape or appearance of the nipple, including turning-in or inversion of the nipple, crusting sores and redness
- Nipple discharge (that is not breast milk)
- Changes in size or shape of a breast or a change to the skin of the breast (such as dimpling or indentation, rash, redness, a scaly appearance or other colour changes)
- Swelling or discomfort in the armpit/s
- Ongoing unusual pain that is not related to the menstrual cycle, persists after your period and only occurs in one breast
Causes and risk factors of HER2 positive breast cancer
There are several lifestyle, environmental and genetic risk factors for breast cancers, including HER2 positive breast cancer.
- HER2 breast cancer is not hereditary. It is caused by the excess production of HER2 protein.
- The risk of breast cancer in general increases if you have breast cancer cases in the family.
- Being overweight or obese increases the risk of developing breast cancer in post-menopausal women, including HER2 breast cancer.
- Living a sedentary lifestyle, smoking, and drinking alcohol can also increase an individual’s risk of developing breast cancer.
- Other risk factors may include ageing, previous breast cancer diagnoses, having dense breasts (ie. having more glandular and fibrous tissue, and less fatty tissue, in the breasts), having radiation to the chest area before the age of 30, beginning menstruation before age 12, and having mutations of genes such as BRCA1, BRCA2 as well as less common mutations in PTEN, PALB2, CHEK2, ATM, CDH1 and P53.
Diagnosis of HER2 positive breast cancer
There are several diagnostic tests that may be used in the detection of HER2 positive breast cancer. It’s important to know whether or not HER2 is present in high amounts in the breast cancer tissue, as this will affect the treatment your doctor chooses to treat the cancer.
IHC (Immunohistochemistry) is used to determine the amount of HER2 protein present. The HER2 cell surface proteins are chemically stained and measured on a scale of 0 to 3+, with a score of 3+ considered HER2 positive. If the results of the IHC test are borderline (termed equivocal) (2+), another test may be done to confirm whether the cancer is HER2 positive or negative.
FISH (Fluorescence In Situ Hybridisation) is more precise than IHC and screens for specific genes or parts of genes in the tumour cell DNA. Cancer cells tend to have an abnormal amount of copies of different genes. In the case of breast cancer, it is used to determine the number of copies of the HER2 gene in the cancer tissue.
INFORM HER2 Dual ISH test
Similar to FISH testing and IHC, the INFORM HER2 Dual ISH test uses a different technology to screen for the HER2 gene in breast cancer tissue and enables the results to be viewed on a light microscope.
Treatment for HER2 positive breast cancer
HER2 positive breast cancer life expectancy is affected by many factors, including the stage at diagnosis and the treatment used. However, several effective HER2 positive breast cancer treatments are available for this subtype and your doctor will choose the right one/s for you based on several factors (for example, whether the cancer is hormone positive or negative).
For most people, HER2 positive breast cancer treatment involves targeted therapies – drugs that specifically aim to block HER2 protein to stop the cancer cells from growing. Patients with HER2 positive breast cancer may also receive a combination of treatments that may include surgery, radiation, chemotherapy, targeted and hormonal therapies (if the tumour is also hormone receptor positive). The drugs used for patients with HER2 positive breast cancer may include:
Trastuzumab (brand name Herceptin)
Most people with HER2 positive breast cancer will be prescribed the drug trastuzumab, which specifically targets the HER2 protein. Trastuzumab is one of the most common targeted therapies for HER2 positive breast cancer. It is a very effective treatment for this type of cancer and is often used in conjunction with other types of treatment. This drug is not effective for women with HER2 negative breast cancer.
Lapatinib (brand name Tykerb)
Lapatinib is administered orally and blocks HER2 cell signalling. It is currently only used for advanced metastatic breast cancer. This means that the cancer has spread from the primary breast tumour site to other parts of the body.
Pertuzumab (brand name Perjeta)
Also used in the treatment of metastatic HER2 breast cancer, pertuzumab is another targeted therapy that binds to the HER2 protein on HER2 positive breast cancer cells preventing them from growing. It can be used prior to and/or after surgery depending on the risk of disease relapse.
T-DM1 (brand name Kadcyla)
T-DM1 (Trastuzumab emtansine) is another targeted therapy used in the treatment of metastatic HER2 breast cancer. It is a type of antibody drug conjugate (ADC), which means two drugs linked together. TDM-1 combines trastuzumab and another type of anti-cancer drug, called emtansine, which induces the death of cancer cells. Combining emtansine with trastuzumab results in cancer cell death specifically at the tumour site and is therefore considered as a tumour specific therapy. Trastuzumab deruxtecan (T-DXd, brand name Enhertu) is a similar ADC to T-DM1, but in this case trastuzumab is linked with another anti-cancer agent called deruxtucan) that is also very effective for some patients with metastatic HER2 positive breast cancer.
Patients undergoing treatment with trastuzumab may also be prescribed neratinib (brand name Nerlynx). This oral medication is given in addition to trastuzumab to maximise its effectiveness as a HER2 positive breast cancer treatment.
In the case of a hormone receptor positive HER2 positive breast cancer, endocrine therapy may also be recommended.
While targeted therapies work by ‘targeting’ the specific factors that induce the growth and spread of cancer cells such as the HER2 protein, chemotherapy may be prescribed in combination with these targeted therapies. Anti-cancer drugs used in chemotherapy attack fast-growing cells – which can include both cancer cells and normal cells. Chemotherapy can be given orally or intravenously and may be prescribed in addition to a HER2 targeting therapy.
HER2 positive breast cancer often responds well to treatment with HER2 targeted therapies, however treatment outcomes vary between individuals and are dependent on the stage, grade and characteristics of the tumour.
Survival rates are dependent on factors such as the stage of the cancer, the hormone status of the cancer as well as treatments chosen and how the cancer responds.
No – HER2 positive breast cancer occurs as a result of excess production of the HER2 protein in breast cancer cells and cannot be inherited.
HER2 breast cancers tend to grow and spread faster than other types of breast cancer. However, they often respond well to HER2 targeted therapies.