Is HER2 Cancer Aggressive?

HER2-positive breast cancer means that the breast cancer cells have a higher than normal amount of HER2 proteins on them. HER2 protein is encoded by the HER2 gene, and mutations or too many copies of HER2 genes make breast cells produce too many HER2 proteins, which fuel cancer cell growth.

Human epidermal growth factor receptor-2 (HER2) is a protein that is normally present in all breast cells and regulates cell growth and division. Excessive HER2 protein in cancer cells makes them grow and divide at an abnormally high rate, resulting in HER2-positive breast cancer.

The most common symptom of most breast cancers, including HER2 breast cancer is a lump in the breast. A painless, hard mass with irregular edges is most likely cancer, but breast cancers can also have a lump that is soft and tender to the touch. Other possible symptoms in the first three stages of breast cancer include:

• Change in the size and shape of the breast
• Swelling of the breast
• Asymmetry in the breast compared to the other
• Skin dimpling or other abnormal changes in the breast’s skin
• Nipple inversion or other nipple abnormalities such as ulceration
• Nipple discharge, especially if bloodstained
• Swollen lymph nodes under the arm or near the collarbone

Symptoms of metastatic cancer depends on where the cancer has spread and can include:

• Breathing difficulties
• Bone pain
• Headache and dizziness
• Jaundice and stomach swelling

All breast cancers are staged by the size of the tumor and extent of spread. Breast cancers are also graded from one to three, based on how abnormal the cancer cells look and how fast they grow. Grade one is low grade cancer and three is high grade which grows and spreads rapidly.

The four stages of breast cancer are:

• Stage I: The tumor is relatively small and localized to the original site with possible spread to the sentinel lymph node, which is the first node the cancer is likely to spread to.
• Stage II: The tumor has grown and spread to a few nearby lymph nodes.
• Stage III: The tumor has grown into many lymph nodes and other breast tissue.
• Stage IV: The cancer has spread (metastatic cancer) to distant parts of the body.

Another classification system is the TMN breast cancer classification, based on Tumor size (T), lymph Node status (N) and distant Metastasis (M). It has many detailed classifications for breast cancers.

Samples of breast tissue are removed during a biopsy or surgery and tested in the laboratory to look for presence of HER2 proteins. Commonly used tests to diagnose HER2 positivity include:

• Immunohistochemistry (IHC) test: IHC test uses a chemical dye that stains HER2 protein and reveals its presence. The HER2 protein levels are scored from zero to three. Zero and one are considered HER2-negative, two is inconclusive and three is positive.
• Fluorescence in situ hybridization (FISH) test: FISH test uses fluorescent pieces of DNA that attach to the HER2 gene and show if there are extra copies. FISH tests are usually performed if the IHC result is inconclusive, because they are more expensive and results take longer.
• Inform Dual ISH test: Inform Dual ISH test uses a stain that makes the HER2 protein change color.

The IHC tests are also used to find if the cancer cells have estrogen receptors (ER) and/or progesterone receptors (PR). A positive result indicates that the cancer grows in response to these two female hormones. 

Breast cancers are categorized into the following groups based on the HER2 and hormone receptor (HR) status:

• Luminal A: ER- and PR-positive, and HER2-negative breast cancer
• Luminal B: ER-positive, PR-negative and HER2-positive breast cancer
• HER2-positive: HR-negative and HER2-positive breast cancer
• Triple positive: ER-, PR- and HER2-positive breast cancer
• Triple negative (basal like): HR- and HER2-negative breast cancer

The chances of successfully treating HER2 breast cancer is high if the cancer is detected in early stages. HER2 cancers, however, are often high grade tumors in stage III at the time of diagnosis. If HER2 cancer has metastasized at the time of diagnosis, it is treatable but not curable in most individuals.

With the development of medications that specifically target HER2 proteins, HER2-positive breast cancers now have a much better outlook than in the past. HER2-positive cancers that have been in remission for five years are less likely to recur.

Treatment for breast cancers is individualized depending on the type, grade, stage, HR and HER2 status, and any gene mutations. Treatment also depends on the age, overall health and whether the woman is menopausal or not. Treatment may be more complicated if the woman is pregnant. Patients also have the option of enrolling for clinical trials for new treatments.

The primary treatment for all types of breast cancers, including HER2 cancers typically include a combination of two or more of the following:

Surgery

Most women have surgery as part of the treatment, and surgical procedures may include:

• Lumpectomy: Removal of the tumor with a healthy margin, in low grade early stage cancers.
• Mastectomy: Removal of a whole breast if the cancer has spread to other breast tissue.
• Lymphadenectomy: Removal of sentinel lymph nodes and/or the lymph nodes under the arm, to be tested for cancer.

Many women also undergo a breast reconstruction surgery after surgery for tumor removal. Surgery may also be useful in some situations in metastatic cancers as palliative care.

Radiotherapy

Radiotherapy is the use of high-energy rays or particles to destroy the cancer cells. Radiotherapy is typically used after surgical removal of cancer, to make sure any remaining cancer cells are destroyed, or if cancer has spread to other parts.

Chemotherapy

Chemotherapy is the use of medications that can kill cancer cells. Chemotherapy is typically used after surgery, to lower the risk of recurrence, or sometimes before surgery to shrink large localized tumors.

Gene expression tests which evaluate the risk of recurrence are often performed to assess the possible benefit of chemotherapy and individualize the treatment plan based on the patient’s needs. Chemotherapy is also used to treat metastatic breast cancers.

Hormone therapy

Hormone therapy is given only if the HER2 breast cancer is also positive for hormone receptors. Hormone therapy involves the use of drugs that block hormone receptors, or drugs/surgical procedures that stop production of estrogen in the body. 

Targeted therapy

Targeted therapy medications for HER2-positive cancers block the activity of HER2 proteins by different means. Targeted therapy is used to treat both early and advanced stages of HER2 cancers. Targeted therapy medications for HER2 cancers include:

• Monoclonal antibodies: Monoclonal antibodies are lab-produced antibodies which specifically attach to HER2 proteins in the cancer cells and stop them from growing. Some commonly used targeted therapy medications are:
  • Trastuzumab (Herceptin)
  • Pertuzumab (Perjeta)
  • Margetuximab-cmkb (Margenza)
• Antibody-drug conjugates: Antibody-drug conjugates are antibodies that target and attach to HER2 proteins, and also carry a chemotherapy drug to kill the HER2-positive cells. Examples include:
  • Ado-trastuzumab emtansine (Kadcyla or TDM-1)
  • Fam-trastuzumab deruxtecan-nxki (Enhertu)
• Kinase inhibitors: HER2 is a type of protein known as kinase, which transmits signals (to grow in the case of HER2) within the cells. Kinase inhibitors stop signaling. Examples of kinase inhibitors are:
  • Lapatinib ditosylate (Tykerb)
  • Neratinib maleate (Nerlynx)
  • Tucatinib (Tukysa)

Survival rates with HER2-positive cancer depends on the stage at the time of diagnosis and response to treatment. The development of targeted therapy has greatly improved survival rates for HER2-positive breast cancer. In advanced stages, HER2-positive cancers respond better to treatment than HER2-negative cancers.

According to recent National Cancer Institute data, the four-year survival rate for combined stages of cancer, based on HR and HER2 status are:

• HR-positive/HER2-negative: 92.5%
• HR-positive/HER2-positive: 90.3%
• HR-negative/HER2-positive: 82.7%
• HR-negative/HER2-negative: 77%

Each person is unique; the data represents the average % survival rate.