Precision Therapy for a Hard-to-Treat Cancer
By Maxine Lipner
Published on June 26, 2023
Medically reviewed by Benjamin Leach, MD
For those with breast cancer, human epidermal growth factor receptor 2 (HER2) status is an important classification that allows for targeted treatment. HER2 is a protein associated with normal cell growth found in some breast tumors.
If a tumor has a lot of HER2 on the surface, it is considered HER2-positive, and if it has none, it is HER2-negative. But, there is also a gray area. If it only has some, this is labeled as HER2-low. Treatment can be targeted to this hormone receptor status.
Until 2022, if someone had HER2-low breast cancer, treatment was limited since approaches that targeted HER2 weren't successful in these tumors.1
A targeted treatment for HER2-low breast cancer was approved in 2022.2 Enhertu (trastuzumab deruxtecan T-DXd) delays disease progression longer and has improved survival rates. This is a big step forward from the days when people with breast cancer with low amounts of HER2 received standard treatment options such as chemotherapy3 or endocrine (hormone) therapy.4
Daniel Llao Calvet / Getty Images
As part of this article, you will learn what targeted therapy for HER2-low breast cancer has to offer, what you need to know about how precision treatment works and how this impacts outcomes, the risks and side effects of HER2-low specific treatment, and other breast cancer treatment options.
Targeted Therapy for HER2-Low Breast Cancer
In combatting breast cancer, oncologists (cancer specialists) got a new tool in the arsenal with the approval of Enhertu for HER2-low breast cancer on Aug. 5, 2022, by the Food and Drug Administration (FDA).2
This approval was based on study results that showed that those with previously-treated metastatic HER2-low breast cancer were progression-free of cancer for significantly longer, with a more extended period of overall survival than those who underwent chemotherapy.5
But this approach will only be used after other approaches are tried. Your oncologist may recommend the use of Enhertu in these circumstances:2
You have breast cancer that has metastasized (spread), and you have undergone chemotherapy for it.
You have undergone chemotherapy to keep your cancer from returning, but despite this, it has come back either during the treatment or within six months of completing chemotherapy.
How Precision Treatment Works
Enhertu is a form of targeted therapy known as an antibody-drug conjugate. The drug has two parts that work together to target cancer cells.
One part of Enhertu is an antibody (immune protein) called trastuzumab that attaches to HER2 on the surface of the tumor cells. HER2 can be found in healthy cells but tends to be found in large amounts on the surface of some cancer cells. By targeting HER2, the treatment mainly affects cancer cells.
Akin to attaching an explosive to a missile, Enhertu also has a chemotherapy component known as deruxtecan (DXd) that is used to kill the tumor cells. Once the antibody attaches to HER2, it can enter the cell and release the potent DXd, killing the cell by damaging its DNA (genetic material).
With this approach, the chemotherapy is, in effect, targeted mainly at cancer cells, mostly sparing the healthy ones.6
Other Breast Cancer Treatments
While the targeted approach can play an important role in treating HER2-low breast cancer, it is by no means the only treatment for those dealing with this condition. Before an oncologist recommends Enhertu, the person with breast cancer will likely undergo other treatments, such as the following.
Chemotherapy
This approach relies on the use of cancer-killing agents. These are injected or infused into the bloodstream and, from there, travel throughout the body. These drugs interrupt cancer cell growth and affect other fast-growing cells in healthy tissues.
Chemotherapy may be given before surgery to shrink tumors and help to keep cancer from returning. Or, it may be administered after tumor removal to proactively mop up any cells that may have traveled elsewhere.7
Is Enhertu Chemotherapy?
Enhertu is a drug with a component that can target HER2 receptors associated with some types of cancer, as well as an attached chemotherapy agent to kill these cancer cells.6 The chemotherapy agent is primarily delivered to cancer cells rather than affecting healthy cells, which differs from traditional chemotherapy agents.
Radiation
With radiation treatment, high-energy particles disrupt breast cancer tumors. The idea is to use these particles to destroy cancer cells. Typically, radiation treatment is used after tumor removal, such as a lumpectomy, to ensure cancer doesn't return. It may also be used after mastectomy (breast removal) if the tumor is particularly large or has spread elsewhere.
Different types of radiation treatment may be tried, including:8
External beam radiation therapy is the most common type. It involves using an external machine that directs the radiation at the tumor.
Brachytherapy is a form of internal radiation that involves putting radioactive seeds into the breast tissue near a tumor. With intracavitary brachytherapy, a device is put temporarily into the breast, and radioactive pellets are placed daily for short periods. With interstitial brachytherapy, hollow tubes are placed near the tumor, and radioactive pellets are inserted into these for a short time each day.
Hormone Therapy
Since some breast tumors can grow as a result of exposure to hormones, it can help to reduce the amount of estrogen and progesterone that are circulating in the system. For example, in around 7 out of 10 cases, exposure to estrogen can cause breast cancer tumors to grow.9 By blocking these effects, hormone treatments can help in a variety of ways.
Hormone therapy can be used to:9
Shrink large tumors so these can be removed surgically more easily
Control and reduce tumors if surgery isn't an option
Help keep cancer from returning after surgery and other treatments such as chemotherapy or radiotherapy.
Help treat tumors that have spread from the breast to elsewhere in the body (secondary breast cancer)
Risks and Side Effects of HER2-Low-Specific Treatment
While Enhertu treatment offers a lot of upsides, it's also important to be aware that it does bring some risks. Enhertu can have the following side effects:10
Nausea
Vomiting
Diarrhea
Constipation
Tiredness
Hair loss
Bone or muscle pain
Risk of harm to a fetus or miscarriage
Risk of developing heart problems
Lung issues such as pneumonia
Risk of infection due to low white blood cell counts
If adverse reactions are mild and resolve in a matter of weeks, such as asymptomatic pneumonia, it may be possible to resume treatment with the same dosage or to reduce this somewhat. But if the adverse reaction is severe, such as developing a case of congestive heart failure, the medication may have to be discontinued.11
How Does Precision Treatment Impact Outcomes?
For some, the use of Enhertu can make a big difference. While this treatment cannot cure cancer, it can buy time and extend survival.
Those in the clinical study group who received this targeted medication were able to avoid disease progression for about 10 months, with an overall survival rate of 23.4 months.5 Meanwhile, those who were given chemotherapy only remained cancer free for around five months, with a survival rate of 16.8 months.12
Summary
Targeted HER2-low breast cancer medication has provided new treatment options for those with this condition. The medication, known as Enhertu, targets cancer cells and delivers medication to these to kill the tumors.
While this therapy can be effective, it is tried after other treatments, such as chemotherapy, hormone treatments, or radiation. When the targeted treatment is given, it can extend survival for many.
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