Understanding HER2 positive Breast Cancer and its Treatment
by Dr. C.H. Weaver M.D. updated 2/2021
HER2 (human epidermal growth factor 2) is a receptor on the surface of breast cells. When HER2 is "turned on" it causes the cells to grow and reproduce. Normal breast cells have 2 copies of the gene that makes HER2. In contrast to normal breast cells some have more than two HER2 genes and/or produce too much HER2. This results in more HER2 receptors on breast cells - a condition doctors refer to as "over expression" Over expression of HER2 leads to increased breast cell production or cancer.
Doctors can test for HER2 with two different tests.
- IHC - measures the number of HER2 receptors on a scale of 1-3. 3 + means there are too many.
- ISH - counts the number of HER2 genes.
HER2 + "positive" breast cancers can be treated with precision cancer medicines that target the HER2 receptor. Approximately 20-25% of breast cancers. These cancers are referred to as HER2-positive.
There are several precision cancer medicines that target HER2 and the use of these medications improves the outcomes of women with both early-stage and advanced HER2-positive breast cancer.
- was the first FDA approved drug to treat HER2 + breast cancer and can be used to treat all HER2 + breast cancers.
- Herceptin in Early Stage Breast Cancer
- Herceptin in Advanced-Metastatic Breast Cancer
Next Generation anti HER2 Precision Cancer Medicines
- Perjeta - targets different part of HER2 than Herceptin
- Nerlynx - TKI that targets HER2 at multiple levels.
- Kadcyla (T-DM1) - combines Herceptin with chemotherapy.
- Enhertu - antibody-drug conjugate FDA approved for advanced disease.
- Tucatinib - FDA approved and highly effective
- Margetuximab - in development.
- Pyrotinib - in development
What are the side effects of HER2 therapies?
- Nausea, diarrhea, skin rash can occur with Herceptin and other anti HER2 treatments.
- Herceptin and side effects to the heart.
Should all HER2 + breast cancers be treated?
- All invasive and metastatic HER 2 positive breast cancers benefit from HER2 directed therapy. Even very small cancers appear to benefit. A U.S. study evaluated the records of 965 women with small cancers that had not been treated with HER2-targeted therapy or chemotherapy. By the end of five years, 6% of women with HER2-negative breast cancer had a recurrence compared with 23% of women with HER2-positive breast cancer.
What is the role of HER 2 in DCIS?
Compared with invasive breast cancer, DCIS more often expresses HER2, however current research does not support the use of human HER2 - directed therapy in DCIS.
- Roses RE, Paulson EC, Sharma A et al. HER-2/neu overexpression as a predictor for the transition from in situ to invasive breast cancer. Cancer Epidemiology, Biomarkers & Prevention. 2009 18: 1386-1389.
- Gonzalez AM, Litton JK, Broglio KR et al. High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller. Journal of Clinical Oncology[early online publication]. November 2, 2009.
- Curigliano G, Viale G, Bagnardi V et al. Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer. Journal of Clinical Oncology [early online publication]. November 2, 2009.
- Burstein HJ, Winer EP. Refining therapy for human epidermal growth factor receptor 2-positive breast cancer: T stands for trastuzumab, tumor size, and treatment strategy. Journal of Clinical Oncology [early online publication]. November 2, 2009.
- NCCN Guidelines Version 3.2013 Ductal Carcinoma in Situ (Accessed on August 07, 2013).
- Allred DC, Clark GM, Molina R, et al. Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol 1992; 23:974.