HER2-negative breast cancer is a type of breast cancer that accounts for about 78% of all breast cancer cases. Its name describes the status of the human epidermal growth factor receptor 2, known as HER2, in the disease.

Not all breast cancer cases are the same. Testing for the HER2 protein helps define key aspects of your illness that affect the type of treatment you receive.

HER2 is a protein that exists on the surface of all breast cells. It supports normal cell growth and repair. Very high levels of HER2 can lead to HER2-positive breast cancer. Breast cells in HER2-negative breast cancer have little HER2 protein.

Some treatments target the HER2 receptors. While these treatments can fight HER2-positive cancer, they would be useless against HER2-negative cancer.

This article describes the symptoms, causes, diagnosis, and treatments related to HER2-negative cancer.

Types of HER2-Negative Breast Cancer

There are two subtypes of HER2-negative breast cancer. They are defined by the status of biomarkers for hormone receptors (HR) for estrogen and progesterone.

HER2 Receptors Status

HER2 receptors exist on both cancerous (malignant) and noncancerous (benign) breast cells. HER2-positive breast cancer cells can have up to 100 times more receptors than HER2-negative or normal breast cells. HER2-positive breast cancer accounts for between 15% and 30% of breast cancer diagnoses.

HER2-negative, HR-positive breast cancer: This is the most common subtype of breast cancer. It accounts for about 68% of female breast cancer cases. It includes tumors that have estrogen, progesterone, or both receptors. When estrogen and progesterone bind to these receptors, these tumors grow.

HER2-negative, HR-negative breast cancer: This is a less common subtype of HR2-negative breast cancer. It represents about 10% of female breast cancer cases. This type of breast cancer is negative for HER2, estrogen, and progesterone receptors. It is also called triple-negative breast cancer.

HER2-Negative Breast Cancer Symptoms

Symptoms of HER2-negative breast cancer don’t differ greatly from symptoms of other types of breast cancer.

HER2-Negative to HR2-Positive Breast Cancer

Over time, some HER2-positive breast cancers can become HER2-negative, and some HER2-negative breast cancers can become HER2-positive. This can happen when cancer recurs, so a biopsy is often advised to retest HER2 status when cancer returns after treatment.

Common physical signs and symptoms linked to all types of breast cancer include:

  • A lump, swelling, or thickening of part or all of the breast
  • Red, dry, flaking, or thickened skin on the nipple or breast
  • Skin dimpling on the breast that makes it resemble an orange peel
  • An inward-turned nipple
  • Nipple discharge (other than breast milk)
  • Scaly, red, or swollen skin in the nipple area or the breast
  • Breast or nipple pain
  • Swollen lymph nodes under the arm or near the collarbone
  • Any change in the normal shape or size of the breast

While these symptoms can occur with all types of breast cancer, they can also be related to noncancerous breast conditions. Contact your healthcare provider if you experience symptoms of breast cancer so you can get an accurate diagnosis as early as possible.

Once diagnosed, HER2-negative breast cancer tends to grow slower, spread less easily, and recur less often than HER2-positive breast cancer.

Causes

The exact causes of breast cancer are unknown. Genetics, lifestyle habits, and environmental factors can contribute to your risk of developing breast cancer.

Up to 10% of breast cancers are caused by hereditary gene defects passed from parent to child. Defects in BRCA1 (breast cancer gene one) or BRCA2 (breast cancer gene two) are responsible for most types of inherited breast cancer.

Having a close relative with a certain type of HER2 breast cancer increases your risk of developing breast cancer, but doesn’t affect your risk of having the same type of HER2 breast cancer. HER2-negative breast cancer occurs when breast cells have little to no HER2 protein.

The HER2 gene is not among the abnormal genes associated with inherited types of breast cancer.

Diagnosis

A diagnosis of HER2-negative breast cancer is usually made secondary to a diagnosis of breast cancer.

The type of test used to confirm a breast cancer diagnosis depends on your symptoms. The most common techniques for diagnosing breast cancer include:

  • Breast ultrasound: A breast ultrasound uses inaudible sound waves to provide high-contrast images of the inside of your breasts without radiation.
  • Diagnostic mammogram: A diagnostic mammogram uses low-dose X-rays to identify abnormal areas of tissue within the breast.
  • Breast magnetic resonance imaging (MRI): A breast MRI uses powerful magnets and the injection of contrast dye to deliver a picture of your breasts without radiation or uncomfortable breast compression.
  • Breast biopsy: A breast biopsy involves the surgical removal of a sample of breast tissue so it can be examined under a microscope. It may be used as a follow-up to abnormal findings in a mammogram, breast ultrasound, or breast MRI.

When breast cancer is confirmed, your healthcare provider will use one of the following tests on a sample of breast tissue removed during a biopsy to identify the HER2 status of your disease:

  • Immunohistochemistry (IHC) test: An IHC test is the most commonly used test to determine whether cancer cells have HER2 receptors and/or hormone receptors on their surface.
  • Fluorescence in situ hybridization (FISH) test: A FISH test examines breast cancer tissue to identify the presence of extra copies of the HER2 gene to determine whether the cancer is HER2 negative or HER2 positive.

Treatment

Identifying the HER2 status of your breast cancer diagnosis is a key factor in determining the most appropriate treatment for your disease. Some treatments target the HER2 protein. While they are useful in treating HER2-positive breast cancer, they are not effective in treating HER2-negative breast cancer.

The treatment most appropriate for HER2-negative breast cancer often depends on HR status. Other considerations include factors such as your disease stage, whether your cancer has spread (metastasized), and your menopause status.

Treatment for HER2-negative breast cancer often starts with surgical removal of the tumor. This can involve one of the following techniques:

  • Lumpectomy
  • Mastectomy
  • Ancillary lymph node biopsy
  • Ancillary lymph node dissection

In HER2-negative, HR-positive cancer, hormonal therapy is often used to block hormones from fueling cancer growth. These treatments include:

  • Nolvadex (tamoxifen)
  • Aromatase inhibitors
  • Ovarian suppression drugs

Treatment for HER2-negative breast cancer may also include targeted therapies, which targets the specific genes, proteins, or tissue environments that contribute to cancer growth. Options include one or more of the following treatments:

  • Ibrance (palbociclib)
  • Afinitor (everolimus)
  • Kisqali (ribociclib)
  • Verzenio (abemaciclib)
  • Piqray (alpelisib)
  • Lynparza (olaparib)
  • Talzenna (talazoparib)
  • Antibody therapy

Depending on individual factors, treatment may also include:

  • Immunotherapy including Tecentriq (atezolizumab) or Keytruda (pembrolizumab) for triple-negative (HER2 negative, HR negative) breast cancer
  • Chemotherapy to destroy cancer cells after surgery
  • Radiation therapy to kill cancer cells

Prognosis

The prognosis for HER2-negative breast cancer varies according to factors specific to your disease and overall condition.

The best survival rates are reported among women with HR-positive, HER2-negative breast cancer. The lowest survival rates are reported among those with HR negative/HER2-negative (triple-negative) subtypes of breast cancer.

According to the National Cancer Institute, the most important factor in determining survival outcomes may be the stage at diagnosis. The stage at diagnosis is defined as one of the following categories:

  • Localized (cancer that is confined to the place it started)Regional (cancer that has spread to nearby lymph nodes, tissues, or organs)Distant (cancer that has spread to distant parts of the body)

If you have HER2-negative, HR-positive breast cancer, the relative survival rate for five years, based on the stage of cancer at diagnosis, is estimated at:

  • 100% for localized cancer90% for regional cancer31% for distant cancer

For HER2-negative, HR-negative breast cancer, the five-year relative survival rate is:

  • 91% for localized cancer65% for regional cancer12% for distant cancer

Coping

Coping with any type of breast cancer involves caring for your physical and emotional needs. It’s essential to recognize that you must address both aspects of care to heal.

Physical changes caused by the disease and treatment may mean that you must accept that you may need temporary help. This can include assistance with tasks ranging from daily household chores to financial assistance with medical expenses.

Emotional changes may make you feel lonely, depressed, and overwhelmed by your condition. Reach out for support from family and friends who are willing to help. Consider joining a breast cancer support group to connect with people dealing with similar challenges. If you can’t find a local, in-person support group, consider joining an online support group.

Generally, take time to care for yourself. This can involve actions like meditation, prayer, or other types of relaxation techniques. Change your diet to include eating healthy, and take time out to exercise. These strategies can help you position your body and mind for optimal treatment outcomes.

Summary

Knowing the HER2 status of your breast cancer is key because some treatments target HER2 receptors. HER2-positive breast cancer has high levels of the HER2 protein, but HER2-negative breast cancer has low to no HER2 protein. Treatments that target HER2 receptors do not affect HER2-negative breast cancers.

The outcome with this type of breast cancer is best when the disease is found early and local to the main cancer site. As the cancer spreads without being treated, average survival rates fall.

A Word From Verywell

The outcomes of all types of breast cancer diagnoses have improved in recent years. Factors such as early detection, consistent screening, and treatments individualized to specific breast cancer types have contributed to this progress.

You can take steps to reduce your risk of developing breast cancer and improve your outcomes if you get it. Making lifestyle changes that include a balanced diet and regular exercise can give your body a healthy foundation and promote better outcomes.

If you qualify, you may benefit from joining a clinical trial. Doing so can give you early access to promising drugs, treatments, or procedures as safely as possible.

Frequently Asked Questions

  • Is having HER2-negative breast cancer better than HER2-positive breast cancer?
  • Every breast cancer is different, with the prognosis most dependent on the size of the breast tumor and stage of disease when diagnosed. HER2-positive breast cancer grows faster, is more likely to extend to lymph nodes, and spreads more easily than HER2-negative breast cancer. However, there are more drugs that specifically target the HER2 receptors found in HER2-positive breast cancer, which has improved the survival rates of this type of breast cancer.
  • Learn More:
  • HER2-Positive vs HER2-Negative Breast Cancer
  • When is hormonal therapy most effective for HR2-negative breast cancer?
  • Hormonal therapy treats tumors that test positive for hormone receptors that fuel their growth. This includes tumors classified as HER2-negative, HR-positive, the most common type of breast cancer. Hormone therapy is usually advised after surgery to lower the risk of cancer recurring.
  • Learn More:
  • Hormone Therapy for Breast Cancer
  • Can HER2 status change over time?
  • Yes. Breast cancers may switch HER2 status, affecting the type of treatment that is most appropriate. Whenever cancer recurs, it’s important to have a breast biopsy to examine the tissue for HER2-negative or positive status before treatment begins.
  • Learn More:
  • HER2 Testing in Breast Cancer

Every breast cancer is different, with the prognosis most dependent on the size of the breast tumor and stage of disease when diagnosed. HER2-positive breast cancer grows faster, is more likely to extend to lymph nodes, and spreads more easily than HER2-negative breast cancer. However, there are more drugs that specifically target the HER2 receptors found in HER2-positive breast cancer, which has improved the survival rates of this type of breast cancer.

Hormonal therapy treats tumors that test positive for hormone receptors that fuel their growth. This includes tumors classified as HER2-negative, HR-positive, the most common type of breast cancer. Hormone therapy is usually advised after surgery to lower the risk of cancer recurring.

Yes. Breast cancers may switch HER2 status, affecting the type of treatment that is most appropriate. Whenever cancer recurs, it’s important to have a breast biopsy to examine the tissue for HER2-negative or positive status before treatment begins.