What Causes HER2-Positive Breast Cancer?

Reviewed on 4/21/2021

Breast cancer is caused by an abnormal growth of cells. HER-2 positive breast cancer is when there are higher than normal levels of a growth-promoting HER2 protein.
Breast cancer is caused by an abnormal growth of cells. HER-2 positive breast cancer is when there are higher than normal levels of a growth-promoting HER2 protein.

Breast cancer occurs when cells in the breast become abnormal and grow out of control. HER2-positive breast cancers are those in which higher than normal levels of a growth-promoting protein known as HER2 are present. 

HER2-positive breast cancers usually grow and spread faster than other breast cancers, but they tend to respond to specific drugs targeting the HER2 protein. 

The exact cause of HER2-positive breast cancer is unknown, but it is believed environment, lifestyle, and genetics may be factors. 

Risk factors for developing breast cancer in general include: 

  • Being a woman
  • Inherited genes, including BRCA1 and BRCA2 and others
  • Family history or personal history of breast cancer
  • Age over 55
  • Physical inactivity
  • Overweight/obesity
  • Alcohol use 
  • Use of hormonal birth control
  • Hormone replacement therapy (HRT) for menopause, particularly estrogen and progesterone (combined hormone therapy)
  • Having a first child after age 30 or having no children
  • Dense breast tissue
  • Ethnicity: White women are slightly more likely to develop breast cancer during their lifetime, but African-American women are more likely to develop breast cancer under age 45
  • Certain benign breast conditions
  • Early onset menstruation (before age 12)
  • Menopause after age 55
  • Radiation to the chest 

What Are Symptoms of HER2-Positive Breast Cancer?

The American Cancer Society’s warning signs and symptoms of breast cancer include:

  • Breast lump
  • Lump in the underarm area (armpit)
  • Swelling or thickening of the breast
  • Irritation or dimpling of the breast skin
  • Pain in any area of the breast
  • Nipple pain
  • Nipple turning inward
  • Changes in the size or shape of the breast
  • Skin changes on the breast: redness, scaliness, flaky skin, or thickening of the nipple or breast skin
  • Nipple discharge that is not breast milk, including blood

How Is HER2-Positive Breast Cancer Diagnosed?

In some cases, a woman may discover a lump or may notice changes in the breast. A doctor will perform a physical exam to look for breast changes such as:

  • A lump in the breast
  • Changes in the size or shape of the breasts
  • Dimpling skin on the breast
  • Pulling in of a nipple
  • Discoloration of breast skin

Tests used to confirm a diagnosis of breast cancer include: 

  • Mammogram (a special type of X-ray)
    • 3D tomosynthesis is a special new type of digital mammogram
  • Breast ultrasound 
  • Breast magnetic resonance imaging (MRI)
    • Not usually used to screen for breast cancer but may be used in the following situations:
      • Screening young women, especially those with dense breasts, who have an increased risk of breast cancer (e.g., mutations in the genes BRCA1 or BRCA2)
      • Screening for breast cancer in women diagnosed with cancer of the lymph nodes (glands) 
      • Screening of women with newly diagnosed breast cancer with extremely dense breasts on mammograms
  • Biopsy, in which samples of tissue from the breast are removed and examined 

Tests used to determine if breast cancer is HER2 positive include:  

  • IHC test (ImmunoHistoChemistry)
  • FISH test (Fluorescence In Situ Hybridization)

QUESTION

A lump in the breast is almost always cancer. See Answer

What Is the Treatment for HER2-Positive Breast Cancer?

Treatment for HER2 positive breast cancer usually involves anti-HER2 therapies (also called HER2 inhibitors or HER2-targeted therapies) that specifically target HER2 receptors. These drugs only work on HER2-postive breast cancer. 

Anti-HER2 therapies include: 

  • Monoclonal antibodies 
    • Trastuzumab (Herceptin, Herceptin Hylecta), which can be given with chemotherapy and sometimes another targeted therapy called pertuzumab (Perjeta)
    • Herzuma, Kanjinti, Ogivri, Ontruzant, and Trazimera are biosimilars to Herceptin
    • Margetuximab-cmkb (Margenza) used in combination with chemotherapy 
    • Pertuzumab (Perjeta) used in combination with Herceptin and chemotherapy 
  • Antibody-drug conjugates 
    • Am-trastuzumab-deruxtecan-nxki (Enhertu) 
      • Used to treat people diagnosed with metastatic HER2-positive breast cancer previously treated with at least two other anti-HER2 medicines
      • Also used to treat HER2-positive breast cancer unable to be removed with surgery 
    • T-DM1 or ado-trastuzumab emtansine (Kadcyla) 
      • Used to treat people diagnosed with HER2-positive metastatic breast cancer that has previously been treated with Herceptin and taxane chemotherapy
      • Can be used after surgery in people diagnosed with early-stage HER2-positive breast cancer treated with Herceptin and taxane chemotherapy before surgery and had residual disease found during surgery
    • Pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) 
      • Used in combination with chemotherapy before surgery for early-stage or inflammatory HER2-positive breast cancer
      • Also used after surgery for early-stage HER2-positive breast cancer with a high risk of recurrence
  • Pan-HER inhibitor 
    • Neratinib (Nerlynx) 
      • Used to treat early-stage HER2-positive breast cancer for an extended period of time after surgery and chemotherapy
      • Also used in combination with chemotherapy to treat advanced-stage and metastatic HER2-positive breast cancer
  • Signal transduction inhibitor 
    • Lapatinib (Tykerb
      • Used to treat advanced or metastatic breast cancer that is HER2-positive in combination with chemotherapy medicines
  • Tyrosine kinase inhibitor 
    • Tucatinib (Tukysa) 
      • Used to treat metastatic or locally advanced HER2-positive breast cancer that can’t be completely removed with surgery, after the cancer has been treated with at least one anti-HER2 medicine. 

HER2-positive breast cancer may also be treated with chemotherapy, surgery, radiation, and other treatments. 

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Reviewed on 4/21/2021
References
https://www.uptodate.com/contents/breast-cancer-the-basics

https://www.uptodate.com/contents/breast-cancer-guide-to-diagnosis-and-treatment-beyond-the-basics

http://www.cancer.org/cancer/breastcancer/overviewguide/breast-cancer-overview-what-causes

https://www.breastcancer.org/