Table of ContentsView AllTable of ContentsHER2-Low MeaningSymptomsDiagnosisTargeted TreatmentIs HER2 Low Good or Bad?
Table of ContentsView All
View All
Table of Contents
HER2-Low Meaning
Symptoms
Diagnosis
Targeted Treatment
Is HER2 Low Good or Bad?
HER2 (human epidermal growth factor receptor 2) is a protein that controls the growth and survival of normal, healthy cells. Some cancers, including breast, can make HER2 in higher-than-normal amounts.
Breast cancersthat make higher-than-normal amounts of HER2 are consideredHER2-positive, whereas breast cancers that make a tiny amount or no HER2 protein areHER2-negative.
HER2-lowdescribes a novel subtype of breast cancer that makes some HER2 protein but not enough to be classified as HER2-positive.
This article highlights the symptoms, diagnosis, and targeted treatment of HER2-low breast cancer, which accounts for around 50% of all breast cancer cases.
Human Epidermal Growth Factor Receptor 2 (HER2)
What Does HER2-Low Mean?
When diagnosed with invasive ormetastatic breast cancer, the HER2 status of thetumor(mass of rapidly dividing cells) will be determined, ultimately guiding treatment decisions.
Invasive breast cancer means the cancer cells have spread to surrounding tissue, whereas metastatic breast cancer has spread to distant parts of the body (e.g., the bones or brain).
HER2-low describes a breast cancer subtype “in between” HER2-positive and HER2-negative. The cancer cells have some HER2 protein on their surfaces but not enough to be considered HER2-positive.
In the past, HER2-low breast cancers were classified and treated as HER2-negative breast cancers because there was insufficient HER2 protein for HER2-targeting drugs to be effective.
However, a HER2-targeted therapy approved in 2022 is effective against HER2-low breast cancer.This offers hope and perhaps more time for people who have exhausted other treatment options.
Besides HER2 status, several other factors are considered when devising a personalized breast cancer treatment plan. Some of these factors include:
Symptoms of HER2-Low Breast Cancer
The symptoms of HER2-low breast cancer are the same as those of HER-2-positive and HER2-negative breast cancer.
The main distinction among the HER2 subtypes is that HER2-positive breast cancers tend to be the most aggressive. The excess HER2 protein on the cancer cells' surfaces makes the tumor rapidly grow and spread (metastasize). HER2-positive breast cancers are also more likely to recur.
HER2-low breast cancer symptoms include:
When to Worry About a Breast Lump
At the time of diagnosis, between 5% and 8% of all people with breast cancer see a healthcare provider for symptoms of metastasis.The most common sites of breast cancer metastasis and their associated symptoms include:
How Breast Cancer Spreads and Recurs
How Is HER2-Low Status Determined?
After a breast cancer tumor is detected, a tissue sample from the tumor is sent for special testing to determine if the cancer cells have high, low, or normal levels of HER2 protein.
The levels of HER2 protein classify a person’s breast cancer subtype and, from there, inform a tailored treatment plan.
What Is Immunohistochemistry?Immunohistochemistry involves apathologist(a doctor specializing in analyzing body tissues) looking at a tissue sample under a microscope and measuring various proteins.
What Is Immunohistochemistry?
Immunohistochemistry involves apathologist(a doctor specializing in analyzing body tissues) looking at a tissue sample under a microscope and measuring various proteins.
Immunohistochemistry(IHC)is the first laboratory test performed to identify HER2 status.
In detecting a person’s HER2 status, immunohistochemistory entails measuring the number of HER2 protein receptors (docking sites) on the surface of breast cancer cells:
FISH detects the gene that codes for the HER2 protein and sees how many copies are present. If FISH is positive (two copies of the gene are present), the cancer isHER2-positive; if negative, the tumor isHER2-low.
HER2 Testing for Breast Cancer and What the Results Mean
HER2-Low Classification: Targeted Treatment
Breast cancer treatment, including the subtype HER2-low, aims to curb the growth and spread of breast cancer cells and prevent the disease from returning.
There are multiple treatment methods for breast cancer, includingsurgery,radiation,chemotherapy,hormone therapy,immunotherapy, andtargeted therapy.
How Breast Cancer Is Treated
Targeted therapies are drugs that “target” specific proteins on breast cancer cells to kill or slow their growth. They differ from chemotherapies because they are directed toward particular cells and not all healthy, fast-growing cells in the body.
HER2-low breast cancer was previously classified and treated as HER2-negative breast cancer. No targeted therapies were available until 2022.
In August 2022, the U.S. Food and Drug Administration approved the first targeted drug for HER2-low breast cancers,Enhertu(fam-trastuzumab deruxtecan).
Enhertu, also known as T-DXd, can be used in adults with unresectable (which refers to something that cannot be surgically removed) or metastatic HER2-low breast cancer who have:
Enhertu is an intravenous (given through the vein) medication consisting of amonoclonal antibody(an artificial protein that binds to a specific target on cell surfaces) chemically connected to a chemo drug. In this case, the monoclonal antibody istrastuzumab, and the chemo drug is deruxtecan.
How Enhertu WorksThe trastuzumb part of Enhertu attaches to HER2 on the surface of breast cancer cells and enters those cells. When inside the cell, the deruxtecan part of Enhertu is released, causingDNAdamage and cell death.
How Enhertu Works
The trastuzumb part of Enhertu attaches to HER2 on the surface of breast cancer cells and enters those cells. When inside the cell, the deruxtecan part of Enhertu is released, causingDNAdamage and cell death.
HER2-Low Breast Cancer Treatment
Breast cancer treatment is complex and requires a personalized approach. HER status, whether negative, positive, or low, is one considered factor, so it cannot be considered wholly “good” or “bad.”
All said, HER2 is certainly a vitalprognostic(measure of outcome) marker in breast cancer. Though HER2-positive cancer was historically associated with poor outcomes, the discovery of HER2-targeted therapies changed its outlook, resulting in better outcomes, including overall survival.
Regarding HER2-low breast cancer, experts are still learning more about this subtype. However, the fact that cancer responds to HER2-targeted therapies, like Enhertu, is promising.
In one trial, nearly 500 participants with previously treated HER2-low metastatic breast cancer were randomized to treatment with Enhertu or chemotherapy.The participants who received Enhertu had around a 50% lower risk of disease progression (worsening) and a 36% lower risk of death than those treated with chemotherapy.
Summary
Though there is still much to learn about HER2-low breast cancer, the discovery of a HER2-targeted therapy called Enhertu (trastuzumab deruxtecan), which is effective against unresectable or metastatic HER2-low breast cancer, offers much hope for current and future breast cancer care.
Understanding Your Breast Cancer Pathology Report
12 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.National Cancer Institute.Definition of HER2 negative.Zhang H, Peng Y.Current biological, pathological and clinical landscape of HER2-low breast cancer.Cancers (Basel).2022;15(1):126. doi:10.3390/cancers15010126Schlam I, Tolaney SM, Tarantino P.How I treat HER2-low advanced breast cancer.Breast. 2023;67:116-123. doi:10.1016/j.breast.2023.01.005National Cancer Institute.Enhertu improves survival for metastatic “HER2-low” breast cancer.Asif HM, Sultana S, Ahmed S, et al.HER-2 positive breast cancer — a mini-review.Asian Pac J Cancer Prev. 2016;17(4):1609-15. doi:10.7314/apjcp.2016.17.4.1609American Cancer Society.Breast cancer signs and symptoms.DeSantis CE, Ma J, Gaudet MM, et al.Breast cancer statistics, 2019.CA Cancer J Clin. 2019;69(6):438-451. doi10.3322/caac.21583Wu Q, Li J, Zhu S, et al.Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study.Oncotarget. 2017;8(17):27990-27996. doi:10.18632/oncotarget.15856Wolff AC, Hammond MEH, Allison KH, et al.Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update.J Clin Oncol. 2018;36(20):2105-2122. doi:10.1200/JCO.2018.77.8738U.S. Food and Drug Administration.FDA approves first targeted therapy for HER2-low breast cancer.Patel A, Unni N, Peng Y.The changing paradigm for the treatment of HER2-positive breast cancer.Cancers (Basel). 2020;12(8):2081. doi:10.3390/cancers12082081Modi S, Jacot W, Yamashita T, et al.Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer.N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.National Cancer Institute.Definition of HER2 negative.Zhang H, Peng Y.Current biological, pathological and clinical landscape of HER2-low breast cancer.Cancers (Basel).2022;15(1):126. doi:10.3390/cancers15010126Schlam I, Tolaney SM, Tarantino P.How I treat HER2-low advanced breast cancer.Breast. 2023;67:116-123. doi:10.1016/j.breast.2023.01.005National Cancer Institute.Enhertu improves survival for metastatic “HER2-low” breast cancer.Asif HM, Sultana S, Ahmed S, et al.HER-2 positive breast cancer — a mini-review.Asian Pac J Cancer Prev. 2016;17(4):1609-15. doi:10.7314/apjcp.2016.17.4.1609American Cancer Society.Breast cancer signs and symptoms.DeSantis CE, Ma J, Gaudet MM, et al.Breast cancer statistics, 2019.CA Cancer J Clin. 2019;69(6):438-451. doi10.3322/caac.21583Wu Q, Li J, Zhu S, et al.Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study.Oncotarget. 2017;8(17):27990-27996. doi:10.18632/oncotarget.15856Wolff AC, Hammond MEH, Allison KH, et al.Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update.J Clin Oncol. 2018;36(20):2105-2122. doi:10.1200/JCO.2018.77.8738U.S. Food and Drug Administration.FDA approves first targeted therapy for HER2-low breast cancer.Patel A, Unni N, Peng Y.The changing paradigm for the treatment of HER2-positive breast cancer.Cancers (Basel). 2020;12(8):2081. doi:10.3390/cancers12082081Modi S, Jacot W, Yamashita T, et al.Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer.N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
National Cancer Institute.Definition of HER2 negative.Zhang H, Peng Y.Current biological, pathological and clinical landscape of HER2-low breast cancer.Cancers (Basel).2022;15(1):126. doi:10.3390/cancers15010126Schlam I, Tolaney SM, Tarantino P.How I treat HER2-low advanced breast cancer.Breast. 2023;67:116-123. doi:10.1016/j.breast.2023.01.005National Cancer Institute.Enhertu improves survival for metastatic “HER2-low” breast cancer.Asif HM, Sultana S, Ahmed S, et al.HER-2 positive breast cancer — a mini-review.Asian Pac J Cancer Prev. 2016;17(4):1609-15. doi:10.7314/apjcp.2016.17.4.1609American Cancer Society.Breast cancer signs and symptoms.DeSantis CE, Ma J, Gaudet MM, et al.Breast cancer statistics, 2019.CA Cancer J Clin. 2019;69(6):438-451. doi10.3322/caac.21583Wu Q, Li J, Zhu S, et al.Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study.Oncotarget. 2017;8(17):27990-27996. doi:10.18632/oncotarget.15856Wolff AC, Hammond MEH, Allison KH, et al.Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update.J Clin Oncol. 2018;36(20):2105-2122. doi:10.1200/JCO.2018.77.8738U.S. Food and Drug Administration.FDA approves first targeted therapy for HER2-low breast cancer.Patel A, Unni N, Peng Y.The changing paradigm for the treatment of HER2-positive breast cancer.Cancers (Basel). 2020;12(8):2081. doi:10.3390/cancers12082081Modi S, Jacot W, Yamashita T, et al.Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer.N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
National Cancer Institute.Definition of HER2 negative.
Zhang H, Peng Y.Current biological, pathological and clinical landscape of HER2-low breast cancer.Cancers (Basel).2022;15(1):126. doi:10.3390/cancers15010126
Schlam I, Tolaney SM, Tarantino P.How I treat HER2-low advanced breast cancer.Breast. 2023;67:116-123. doi:10.1016/j.breast.2023.01.005
National Cancer Institute.Enhertu improves survival for metastatic “HER2-low” breast cancer.
Asif HM, Sultana S, Ahmed S, et al.HER-2 positive breast cancer — a mini-review.Asian Pac J Cancer Prev. 2016;17(4):1609-15. doi:10.7314/apjcp.2016.17.4.1609
American Cancer Society.Breast cancer signs and symptoms.
DeSantis CE, Ma J, Gaudet MM, et al.Breast cancer statistics, 2019.CA Cancer J Clin. 2019;69(6):438-451. doi10.3322/caac.21583
Wu Q, Li J, Zhu S, et al.Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study.Oncotarget. 2017;8(17):27990-27996. doi:10.18632/oncotarget.15856
Wolff AC, Hammond MEH, Allison KH, et al.Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update.J Clin Oncol. 2018;36(20):2105-2122. doi:10.1200/JCO.2018.77.8738
U.S. Food and Drug Administration.FDA approves first targeted therapy for HER2-low breast cancer.
Patel A, Unni N, Peng Y.The changing paradigm for the treatment of HER2-positive breast cancer.Cancers (Basel). 2020;12(8):2081. doi:10.3390/cancers12082081
Modi S, Jacot W, Yamashita T, et al.Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer.N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
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