HER2-positive cancer cells produce HER2 protein that stimulates cell growth. Stage 4 HER2-positive esophageal cancer has a poor outlook, but some targeted therapy drugs may help people live longer.

According to estimates from the American Cancer Society (ACS), about 17,030 men and 4,530 women in the United States will receive a diagnosis of esophageal cancer in 2023. Roughly half of these people will have cancer spread to distant body parts when they’ve received a diagnosis.

Human epidermal growth factor receptor 2 (HER2) is a protein produced by some cancer cells. Cancer that tests positive for this protein is called HER2-positive esophageal cancer.

Stage 4 HER2-positive esophageal cancer means that cancer has spread extensively into the tissue around your food pipe (esophagus) or to distant body parts.

Stage 4 esophageal cancer is difficult to treat and has a poor outlook. It’s often treated with a combination of chemotherapy and targeted therapy drugs such as trastuzumab (Herceptin).

Keep reading to learn more about the treatment and outlook for people with HER2-positive stage 4 esophageal cancer.

Language matters

We use “women” and “men” in this article to reflect the terms that have been historically used to gender people. But your gender identity may not align with how your body responds to this disease. Your doctor can better help you understand how your specific circumstances will translate into diagnosis, symptoms, and treatment.

Was this helpful?

HER2 is a protein that promotes the growth and division of cells. HER2-positive cancer cells produce too much of this protein, which can cause them to grow quickly.

Knowing whether your cancer is HER2-positive helps doctors determine whether you may respond to some targeted therapy drugs. Targeted therapy drugs are like chemotherapy drugs, but they largely destroy cancer cells without damaging healthy cells.

Other types of HER2-positive cancers, such as breast and stomach cancers, may have a poorer outlook than HER2-negative cancers. But research suggests that HER2-positive esophageal cancer isn’t linked with poorer survival rates.

How common is HER2-positive esophageal cancer?

According to the National Cancer Institute, esophageal cancer makes up about 1% of cancers in the United States. About 4 out of 100,000 people develop esophageal cancer each year. Esophageal adenocarcinoma, a type of esophageal cancer, makes up about 80% of these cancers.

Roughly 17% of esophageal adenocarcinomas are HER2-positive.

The next most common type of esophageal cancer in the United States is esophageal squamous cell carcinoma.

In a 2021 study, researchers estimated that 8.6–10% of esophageal squamous cell carcinomas were HER2-positive among 1,505 people.

Was this helpful?

Doctors divide esophageal cancer into stages depending on how far it’s spread. The most common staging system doctors use is the American Joint Committee on Cancer (AJCC)’s TNM system.

Learn more about esophageal cancer stages.

Stage 4 is the highest stage of esophageal cancer. It can be further broken into stage 4A and stage 4B:

4ACancer has not spread to distant tissues but has grown into:

• the covering of your lungs, covering of your heart, or your diaphragm.


• your windpipe, aorta, spine, or other major structures in the area around your esophagus and no more than 6 nearby lymph nodes.


• any layer of your esophagus and 7 or more nearby lymph nodes.
4BCancer has spread to distant lymph nodes or organs.

Researchers have found that some targeted therapy drugs improve the survival of people with HER2-positive adenocarcinoma. These drugs include:

NameDrug classUsual administration
trastuzumab (Herceptin)monoclonal antibodyonce every 3 weeks with chemotherapy through intravenous (IV) infusion
fam-trastuzumab deruxtecan (Enhertu)antibody-drug conjugateonce every 3 weeks through IV infusion

Trastuzumab (Herceptin) with chemotherapy is the standard first-line treatment for people with HER2-positive cancer spread to distant tissues.

In 2021, the FDA granted accelerated approval of another targeted therapy drug called pembrolizumab (Keytruda). This drug, in combination with trastuzumab and chemotherapy, is now approved to treat HER2-positive cancer that’s not surgically treatable.

Fam-trastuzumab deruxtecan (Enhertu) is the second-line therapy. If you have HER2-positive cancer and your condition worsens while taking trastuzumab (Herceptin), your doctor may recommend fam-trastuzumab deruxtecan.

Healthcare professionals currently do not use targeted therapy to treat squamous cell esophageal cancer.

New targeted therapy and immunotherapy drugs are in various points of development for treating HER2 cancer.

Is HER2-positive esophageal cancer curable?

HER2-positive esophageal cancer may be curable if it’s contained in your esophagus or surrounding tissues. Stage 4 esophageal cancer usually isn’t considered curable. Treatment usually aims to help people live longer and lower their symptoms.

Learn more about the effectiveness of nonsurgical treatments for esophageal cancer.

Was this helpful?

People with esophageal cancer that has spread to distant tissues tend to have a poor outlook. ACS says that people with distant spread have a 5-year relative survival rate of about 6%. This means they live at least 5 years, but only about 6% as often as people without esophageal cancer.

Cancer contained in the esophagus or surrounding tissue is easier to treat and has a better outlook.

The American Cancer Society and National Cancer Institute don’t use the AJCC’s TNM staging system for reporting survival statistics. Instead, they divide the cancer into three categories depending on how far it has spread.

Here’s a look at the relative survival rates of esophageal cancer in the United States for 2012–2018, as per ACS:

Stage5-year relative survival rate
all stages21%

In a 2018 study, researchers found no significant difference in survival between people with HER2-positive or HER2-negative esophageal cancer.

Learn more about esophageal cancer survival rates.

Who’s at risk of developing esophageal cancer?

Risk factors for esophageal cancer include:

Was this helpful?

HER2 is a protein produced by healthy cells and some cancer cells that stimulate cell growth. Knowing whether your cancer is HER2-positive helps doctors determine whether you may respond to certain targeted therapy drugs.

Stage 4 esophageal cancer tends to be very difficult to treat. Treatment often focuses on helping improve your overall survival time and lowering symptoms.