If you have been told you have a HER2-positive (HER2+) breast cancer, you may be wondering what that means, exactly. What is HER2? Why is it important? How does a doctor test for HER2? How will this impact treatment decisions and even long-term survival?
HER2 stands for “human epidermal growth factor receptor 2.” It is a growth-promoting protein that is found on the outside of all breast cells—even healthy ones. Breast cancer cells with higher than normal levels of the HER2 protein are called HER2+. This and the hormone receptors estrogen and progesterone are referred to as “prognostic factors” and are very important features of breast cancer cells that determine what treatments may work best.
HER2+ breast cancers are more aggressive and grow faster than HER2-negative breast cancers. Until the mid-1990s, having a HER2+ breast cancer was very stressful because no disease-specific treatment was available. However, since then researchers have developed specific treatments that target these proteins and have been shown to be effective against HER2+ breast cancer.
If you have a HER2+ breast cancer, you are not alone. HER2 is a crucial factor involved in approximately 25% of breast cancer cases. It is also one of the most reliable tumor markers to determine prognosis and treatment options.1 Let’s take a closer look at HER2, how it is detected, and what it could mean for you.
Testing for HER2
Pathologists conduct a test on a tumor tissue sample (taken through biopsy or during surgery) to determine if abnormal levels of HER2 are present. Two of the most common tests are the FISH (fluorescence in situ hybridization) test, a laboratory test used to find out if there are high levels of the HER2 gene in breast cancer cells, and the IHC (immunohistochemistry) test, a laboratory test that determines if there is too much HER2 protein in breast cancer cells.
When reading the results on a pathology report, the information may be confusing because usually the IHC test is performed first, and if it shows that there may be an overproduction of the HER2 protein, then the FISH test is performed to confirm this. If, however, the IHC test gives a negative result (meaning, there is not an overproduction of the HER2 protein), then the FISH test is not performed.
HER2-targeted therapies have radically improved the treatment options and, most importantly, the outcomes for patients with HER2+ breast cancer. There are several reliable drugs (called monoclonal antibodies) available to treat a person with HER2+ breast cancer. These drugs are given by an intravenous infusion. The medicines most often prescribed are Herceptin (trastuzumab) and Perjeta (pertuzumab). Herceptin is often given with chemotherapy, but it may also be used alone (especially if chemotherapy was tried alone first). Herceptin is given for 1 year, so it continues to be administered after chemotherapy treatments are completed. Perjeta, when administered with Herceptin, is often used for 6 to 12 months, and is often used before and continued after surgery along with chemotherapy.
Other Medications for HER2+ Breast Cancer
Nerlynx (neratinib) is a kinase inhibitor approved by the FDA in 2017. Nerlynx is the first extended adjuvant therapy for HER2+ breast cancer (“adjuvant” means a treatment that is given after the initial treatment). Nerlynx is often used in people who have been previously treated with a regimen that includes the drug Herceptin.2
This type of treatment can be effective in slowing the course of the disease and is generally used when the breast cancer has spread beyond the breast (stage IV metastatic breast cancer).3 Kadcyla (ado-trastuzumab emtansine) is an antibody-drug conjugate, a medicine that combines a targeted therapy, in this case trastuzumab, with chemotherapy. This medicine assists in sending the chemotherapy medicine straight to the cancer cells. Kadcyla is approved by the FDA for people with metastatic disease.
The Benefit of Knowing
I know that being diagnosed with HER2+ breast cancer is stressful. Yes, HER2+ breast cancer tends to be a more aggressive cancer. However, you have the advantage of 3 decades of research and clinical trials that have made it possible for people today to receive targeted drugs that are highly effective in treating this type of breast cancer. I hope this knowledge helps to empower you, strengthen you, and give you hope for your future.
- Tolaney SM. Standard-of-care treatment for HER2+ MBC after progression on taxane-trastuzumab T-DM1. Medscape. https://decisionpoint.medscape.com/oncology/viewarticle/917013. December 6, 2019.
- US Food and Drug Administration. FDA approves new treatment to reduce the risk of breast cancer returning. www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-reduce-risk-breast-cancer-returning. July 17, 2017.
- Barfield RM, Kim YC, Chuprakov S, et al. A novel HER2-targeted antibody–drug conjugate offers the possibility of clinical dosing at trastuzumab-equivalent exposure levels. Mol Cancer Ther. 2020;19:1866-1874.
Commonly Asked Questions
Are you sure my cancer is HER2+?
The test performed by a pathologist determines the HER2 status of the breast cancer. In some cases, there may be a “borderline” reading of HER2. With IHC testing, a score of 0 or 1+ is negative, 2+ is borderline, and 3+ is positive. In borderline cases, the FISH test will be performed. Your doctor will order this additional test if needed and will use these results to determine the best treatment path moving forward.
Is HER2+ breast cancer aggressive?
The overexpression of the HER2 protein makes this a more aggressive cancer because HER2 encourages cell growth. Keep in mind, however, that the targeted therapies available are designed specifically to combat HER2+ breast cancer.
Is there a clinical trial I should consider?
There are several clinical trials that aim to develop new and better treatments for HER2+ breast cancer. The HER2CLIMB trial is for people with HER2+ metastatic breast cancer and people with HER2+ breast cancer with stable and active brain metastases. Two trials, called KAITLIN and ATEMPT, are for people with early-stage HER2+ breast cancer. If you are interested in participating, you should speak with your oncologist.
Will I be able to work?
This is dependent on many factors, including the type of work and length of treatment, as well as financial considerations. Chemotherapy often has side effects of varying severity, but it is possible to manage the side effects with medication and other interventions. Some women may be able to work from home on a part-time basis, whereas others may need to take advantage of disability coverage during treatment. It is best to explore options with a human resources representative and your nurse navigator.
How effective is the treatment?
The good news is that treatments such as chemotherapy plus Herceptin have increased early-stage HER2+ breast cancer survival rates. For example, 93% of patients are disease-free 7 years later; 70% to 75% are disease-free at 10 years; and overall survival at 10 years is 80% to 85%.1 So does that mean that people only live 10 years at best? No! It means that the research studies have only measured up to 10 years. There are many women living normal, healthy lives beyond their 10-year survivorship anniversary.
- Oncology Learning Network. Insights from the San Antonio Breast Cancer Symposium. Sara Hurvitz, MD, Discusses Trials on Tucatinib Therapy for HER2+ Metastatic Breast Cancer. www.oncnet.com/videos/sara-hurvitz-md-discusses-trials-tucatinib-therapy-her2-metastatic-breast-cancer. February 15, 2021.