Breast cancer HER2 The difference between positive and negative and their risks

Breast cancer is one of the most common types of cancer among women, and the presence of the HER2 receptor plays a significant role in determining the severity of the disease and treatment options. Knowing whether the cancer is HER2-positive or HER2-negative helps doctors choose the most appropriate treatment and assess the rate of disease progression. In this article on Dalyli Medical, we will explore the difference between these two types, their respective risks, and the most effective treatments available for each case, in a clear and easy-to-understand manner.

What is HER2 Testing?

HER2 testing is a medical test used to determine if the breast cancer cells have an increased amount of the HER2 protein or if there is an overexpression of the HER2 gene. The presence of this protein plays a crucial role in deciding the most suitable treatment for the patient.

How long do the results take?

Typically, the results are available within 3 to 7 days, depending on the laboratory and the type of test used.

Understanding HER2 Test Results

HER2 Positive (+): This means the tumor has high levels of the HER2 protein, which makes treatments like trastuzumab effective.
HER2 Negative (-): The tumor does not have an excess of the HER2 protein, and treatment will be chosen based on other characteristics of the cancer.
Equivocal Results: Sometimes, the result may be unclear (2+), and additional tests like FISH may be required to confirm the result.

Does a HER2 Positive Tumor Need Special Treatment?

Yes, HER2-positive tumors often require targeted therapy in addition to chemotherapy for the best results.

Can HER2 Results Change Over Time?

In some cases, the HER2 status might differ between the primary tumor and recurrent or metastatic tumors. Therefore, if the cancer recurs or spreads, HER2 testing might be repeated.

Is HER2 Testing Painful?

The test itself is not painful because it is done on a tissue sample. However, the process of obtaining the sample (through biopsy or after surgery) might cause some mild discomfort.

Is HER2 Testing Only for Breast Cancer?

No, HER2 testing can also be used for other cancers, such as stomach, esophageal, or lung cancer, if there is a possibility that the cells may be affected by HER2.

Is HER2 Testing Done Immediately After Diagnosis?

Yes, it's crucial to perform the HER2 test right after cancer diagnosis because it determines the most appropriate targeted treatment and influences the overall treatment plan.

Can an Old Biopsy Sample Be Used for HER2 Testing?

In some cases, an old tissue sample stored in the lab can be used for testing if the HER2 test was not done previously or to confirm the result.

Does HER2 Testing Affect the Choice of Chemotherapy?

Yes, if the tumor is HER2-positive, targeted therapy is often added to chemotherapy for the best outcome.

Can a Tumor Be Partially HER2 Positive?

Yes, sometimes only a portion of the tumor cells may show high HER2 levels. In these cases, additional tests may be needed to determine the exact percentage of HER2-positive cells.

Are There Blood Tests for HER2?

Currently, HER2 testing is primarily done on tissue samples, but there are emerging blood tests being used to monitor the effects of targeted therapies. However, these blood tests are not a substitute for tissue testing.

Does HER2 Status Affect Cancer Prognosis or Severity?

Yes, HER2-positive tumors tend to be more aggressive, but with the right targeted therapy, the chances of successful treatment are much higher.

Can Children or Young Adults Have HER2 Testing?

Typically, HER2 testing is performed on adults with breast cancer. However, in rare cases where a child has a cancer that may be affected by HER2, testing may be done.

Are There Any Side Effects from HER2 Testing?

No, there are no side effects from the HER2 test itself as it is done on a tissue sample or biopsy, and there is no pain or complication after the test. The only potential discomfort is from obtaining the tissue sample.

Can HER2 Status Change with Treatment?

Yes, in some cases, the HER2 status may change with treatment or when the cancer recurs. This is why testing may be repeated during follow-up or relapse to determine the best course of treatment.

How Can You Determine if a Tumor is HER2 Positive or Negative?

HER2 testing is done on tissue samples taken from a biopsy or after surgery using a technique called immunohistochemistry (IHC).

0 or 1+ → Negative Result
3+ → Positive Result
2+ → Indeterminate Result, further testing like FISH may be required.

It’s important to review your pathology report for detailed results.

Is There a Special Treatment for HER2-Positive Breast Cancer?

HER2-positive tumors led to the development of targeted therapies. The most well-known of these is trastuzumab (Herceptin®), which has become the standard treatment in both early and advanced stages.

In recent years, new drugs have been developed to target HER2, improving outcomes and reducing the risk of recurrence.

HER2’s Role in Cancer Growth

HER2 (Human Epidermal Growth Factor Receptor 2) is a protein found on the surface of cells and plays a role in cell growth and division. In cancer cells, HER2 is often overexpressed, which causes rapid tumor growth, but it also makes the tumor more responsive to targeted therapies.

Types of HER2 Tests

IHC (Immunohistochemistry) Test
- Purpose: Measures the amount of HER2 protein on the surface of cells.
- Results:
  - 0 or 1+ → Negative
  - 2+ → Indeterminate (needs further testing)
  - 3+ → Positive
- Advantages: Most commonly used, quick, and inexpensive.
FISH (Fluorescence In Situ Hybridization) Test
- Purpose: Detects the number of HER2 gene copies in the cells.
- When Used: If IHC result is 2+ (indeterminate).
- Advantages: Highly accurate, definitive (positive or negative).
CISH or SISH Test
- Purpose: Similar to FISH, but slides are read using a light microscope instead of fluorescence.
- Advantages: Accurate, allows for preservation of slides for later review.
PCR Genetic Test
- Purpose: Measures genetic activity or HER2 gene expression.
- Advantages: Useful for research, less commonly used in routine diagnostics.

Which Test is Best?

IHC is always the first test performed. If the result is 2+, FISH is used for confirmation as it is more accurate.

Who Should Have HER2 Testing and Why is it Done?

Who Should Be Tested for HER2?
HER2 testing is essential for diagnosing and treating certain cancers because it helps determine if the tumor will respond to targeted therapies like trastuzumab (Herceptin). Those who should undergo HER2 testing typically include:

Breast Cancer Patients
- Invasive Breast Cancer: Whether early or advanced stages.
- Recurrent or Metastatic Breast Cancer: To decide the best treatment plan.
- Male Breast Cancer: Although rare, it follows the same protocol for testing.
Stomach or Gastroesophageal Junction Cancer Patients
- HER2 testing is critical for advanced or metastatic stomach cancer or esophageal junction cancers that may respond to HER2-targeted therapies.
Patients with Indeterminate Results (Equivocal)
- If IHC is 2+, additional tests like FISH are required to clarify the result.
Patients Who Did Not Respond to Traditional Treatments
- If hormonal or chemotherapy treatments fail or if new changes are seen after recurrence, HER2 testing can help determine an appropriate course of treatment.
New Biopsy Samples
- When a new biopsy is taken from a tumor or metastatic site, HER2 testing is recommended because HER2 levels may change between the initial and new tumor.

Why Is HER2 Testing Done?

Accurate Tumor Classification
- High HER2 levels help classify whether the tumor is HER2-positive or negative, which is crucial for selecting the right treatment.
Choosing the Right Treatment
- HER2-positive tumors respond well to targeted treatments such as trastuzumab (Herceptin) and pertuzumab.
Assessing Tumor Aggressiveness
- HER2-positive tumors are typically more aggressive and may grow faster, so early intervention with targeted therapy is essential.
Determining Chemotherapy Response
- Results from HER2 testing help determine if chemotherapy alone is sufficient or if targeted treatment is necessary.
Monitoring Cancer Progression During Treatment
- HER2 status may change during treatment or disease progression, so retesting is sometimes needed during relapse or metastasis to adjust treatment.
Ensure Treatment is Cost-Effective
- Targeted HER2 therapies are costly, so testing ensures that the patient will benefit from them.
Assessing Tumors Not Responding to Traditional Treatment
- If a tumor does not respond to standard treatments or shows unusual growth patterns, HER2 testing helps identify new treatment pathways.

Cancers Associated with HER2 Overexpression

HER2 overexpression or gene amplification is not limited to breast cancer. It can occur in several types of cancers, making the tumors more aggressive when HER2 is high. These cancers include:

Breast Cancer
- The most common cancer associated with HER2 overexpression, found in 15-20% of cases. HER2 testing is crucial for selecting the appropriate targeted treatment.
Stomach Cancer
- HER2 overexpression is found in 10-20% of advanced or metastatic cases, and testing is important for determining if targeted therapy is appropriate.
Gastroesophageal Junction Cancer (GEJ)
- Similar to stomach cancer in terms of HER2 overexpression. HER2 testing is recommended, especially in advanced stages.
Esophageal Cancer
- Some types, especially adenocarcinomas, may show HER2 overexpression.
Other Rare Cancers
- Lung Adenocarcinoma
- Ovarian Cancer
- Cervical Cancer
- Colorectal Cancer
For these cancers, HER2 testing is usually done when suspected by the physician.

Stages of HER2 Testing

HER2 testing involves precise steps to ensure accurate results that will guide the treatment plan:

Sample Collection
- A sample is typically taken from the tumor during a biopsy or surgery and sent to the lab for analysis.
Sample Preparation
- The tissue sample is prepared under a microscope and treated with chemicals to preserve the cells and tissues.
Laboratory Testing
- There are two main methods used for testing:
  - IHC Test: Measures the amount of HER2 protein on cancer cell surfaces.
  - FISH Test: Used if IHC is indeterminate to measure the number of HER2 gene copies in the cancer cells.

Results:

IHC: 0 or 1+ (Negative), 2+ (Indeterminate, further testing needed), 3+ (Positive).
FISH: Positive (Increased copies of the HER2 gene), Negative (Normal copies, no targeted therapy).

4. Review of Results by the Oncologist

Determine if the tumor is HER2 positive or negative.
Develop a treatment plan: This could involve conventional therapy, targeted therapy, or a combination of both.

5. Making the Treatment Decision

HER2 Positive: The patient may benefit from trastuzumab (Herceptin) or pertuzumab (Perjeta).
HER2 Negative: Only conventional treatments like surgery, chemotherapy, or radiation therapy are used.

Conditions for Performing HER2 Testing

To ensure the accuracy of the HER2 test results, several conditions need to be met:

New Cancer Diagnosis:
- The test is conducted when breast cancer, stomach cancer, or any other cancer known to be affected by HER2 is diagnosed.
- Objective: To determine if the tumor is HER2 positive to decide the most suitable treatment.
Availability of a Valid Tissue Sample:
- The tissue is taken from the tumor through biopsy (Biopsy) or partial/full surgical removal of the tumor.
- The sample should be well-preserved and undamaged to ensure accurate results.
Patient's Health Status:
- The patient must be able to undergo the test.
- It's advised to inform the doctor about any medications or health conditions that might affect the biopsy or the testing process.
Patient's Informed Consent:
- Informed consent must be obtained from the patient after explaining the purpose and importance of the results for treatment.
Retesting When Necessary:
- If the results are unclear or the sample is insufficient, the test may need to be repeated with a new tissue sample.

Interpreting HER2 Test Results in Simple Terms

HER2 Positive (Positive):
- Meaning: The cancer cells contain an excess of HER2 receptors or the HER2 gene.
- Impact: The tumor is more aggressive but responds well to targeted treatments like trastuzumab (Herceptin).
- Next Steps: Targeted therapy (e.g., trastuzumab) will be prescribed alongside chemotherapy or surgery.
HER2 Negative (Negative):
- Meaning: The cancer cells do not have an elevated amount of HER2.
- Impact: The tumor is less aggressive and does not benefit from HER2-targeted drugs.
- Next Steps: Treatment will be based on the cancer's subtype and the patient's health.
Indeterminate Results (Equivocal):
- Meaning: The test did not definitively determine whether the tumor is HER2 positive or negative.
- Next Steps: Usually, a second test like FISH is conducted to confirm the results.

Tips After Knowing HER2 Results

Discuss the Results with the Oncologist: To understand the most appropriate treatment plan.
If Positive: Ask about targeted treatments and their benefits.
If Negative: Focus on alternative treatments based on the cancer subtype.

Treatment Options for HER2-Positive Breast Cancer

Targeted Therapy:
- These therapies attack cancer cells that have HER2 receptors directly:
  - Trastuzumab (Herceptin): Inhibits the HER2 receptor and slows down cell growth, usually given intravenously every 3 weeks.
  - Pertuzumab (Perjeta): Used in combination with trastuzumab for advanced cases or before surgery to reduce tumor size.
  - T-DM1 (Ado-Trastuzumab Emtansine): A drug that combines trastuzumab with chemotherapy to deliver the treatment directly to affected cells.
  - Lapatinib: An oral drug used for cases resistant to prior treatments or advanced cases.
Chemotherapy:
- Often given along with targeted therapy to improve results.
- It can be used before surgery (Neoadjuvant) to shrink the tumor.
- Examples: Doxorubicin, Cyclophosphamide, or Taxanes.
Surgery:
- Partial or full breast removal depending on the tumor's size and stage.
- Typically, surgery precedes or follows chemotherapy or targeted therapy to eliminate remaining cancer cells.
Radiation Therapy:
- Used after surgery, especially if the tumor is large or the breast is partially removed.
- Reduces the likelihood of cancer recurrence in the breast or surrounding areas.
Hormonal Therapy:
- Only used if the tumor is hormone receptor-positive (e.g., estrogen or progesterone).
- Examples: Tamoxifen or Aromatase Inhibitors.
Follow-up and Support:
- Regular tests (blood tests, scans, MRIs) to monitor progress.
- Psychological support and proper nutrition to improve quality of life during treatment.

Tips Before HER2 Testing

Check the Sample:
- Ensure the biopsy sample is well-preserved in the lab. If there are multiple biopsies, ask the doctor which one is best suited for the test.
Inform the Doctor About Previous Medications:
- Tell your doctor about any prior chemotherapy or radiation, as it may affect the test results.
Ask About the Test:
- Inquire about the testing method, the type of sample needed, and the time it takes for results.
Avoid Excess Stress:
- The test is done on a tissue sample, so there is no additional pain. Focus on staying calm before the sample is taken.

Tips After HER2 Testing

Be Patient While Waiting for Results:
- Results usually take a few days, so try to remain calm while waiting for the doctor's report.
Follow-up with the Doctor:
- Once the results are out, consult your doctor to understand:
  - The tumor type.
  - HER2 positivity.
  - How the result impacts the treatment plan.
Prepare for Targeted Treatment:
- If the result is HER2 positive, you may be prescribed targeted therapies like trastuzumab or similar drugs.
Don’t Worry About the Test Itself:
- The test uses a previously taken biopsy sample, so there are no additional complications after the test.
Document Information:
- Keep a copy of your test results and discuss them with your doctor during any treatment changes or potential relapse.