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What Causes Her2 Negative Breast Cancer

What Do The Results Mean

Updates on hormone receptor-positive HER2-negative breast cancer

If HER2 protein levels are higher than normal or extra copies of the HER2 gene are found, it probably means you have HER2-positive cancer. If your results show normal amounts of HER2 protein or the normal number HER2 genes, you probably have HER2-negative cancer.

If your results were not clearly positive or negative, you will probably get retested, either using a different tumor sample or using a different testing method. Most often, IHC is done first, followed by FISH . IHC testing is less expensive and provides faster results than FISH. But most breast specialists think FISH testing is more accurate.

Treatments for HER2-positive breast cancer can substantially shrink cancerous tumors, with very few side effects. These treatments are not effective in HER2-negative cancers.

If you are being treated for HER2-positive cancer, normal results may mean you are responding to treatment. Results that show higher than normal amounts may mean your treatment is not working, or that cancer has come back after treatment.

What Are The Stages Of Her2 Breast Cancer

All breast cancers are staged by the size of the tumor and extent of spread. Breast cancers are also graded from one to three, based on how abnormal the cancer cells look and how fast they grow. Grade one is low grade cancer and three is high grade which grows and spreads rapidly.

The four stages of breast cancer are:

  • Stage I: The tumor is relatively small and localized to the original site with possible spread to the sentinel lymph node, which is the first node the cancer is likely to spread to.
  • Stage II: The tumor has grown and spread to a few nearby lymph nodes.
  • Stage III: The tumor has grown into many lymph nodes and other breast tissue.
  • Stage IV: The cancer has spread to distant parts of the body.

Another classification system is the TMN breast cancer classification, based on Tumor size , lymph Node status and distant Metastasis . It has many detailed classifications for breast cancers.

What Do The Test Results Mean

The results of HER2 testing will guide you and your cancer care team in making the best treatment decisions.

It is not clear if one test is more accurate than the other, but FISH is more expensive and takes longer to get the results.;Often the IHC test is done first.

  • If the IHC result is 0 or 1+, the cancer is considered HER2-negative. These cancers do not respond to treatment with drugs that target HER2.
  • If the IHC result is 3+, the cancer is HER2-positive. These cancers are usually treated with drugs that target HER2.
  • If the IHC result is 2+, the HER2 status of the tumor is not clear and is called “equivocal.” This means that the HER2 status needs to be tested with FISH to clarify the result.

Triple-negative breast tumors dont have too much HER2 and also dont have estrogen or progesterone receptors. They are HER2-, ER-, and PR-negative. Hormone therapy and drugs that target HER2 are not helpful in treating these cancers. See Triple-negative Breast Cancer to learn more.

Triple-positive breast tumorsare HER2-, ER-, and PR-positive. These cancers are treated with hormone drugs as well as drugs that target HER2.

Our team is made up of doctors and;oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Revised: September 20, 2019

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Why Receptor Status Matters

Breast cancer is not a single disease, and researchers now have the ability to break down breast cancer into different subtypes based on the receptor status of the tumors. Among the variations between different types of breast cancers are the proteins found on cell surfaces, which are involved tumor growth. These proteins are related to the genetic material of cancer cells.

For example, with estrogen receptor-positive;breast cancer, estrogen binds to specific receptors on breast cancer cells, stimulating proliferation. Similarly, HER2 receptors on the surface of breast cancer cells are stimulated by HER2 protein, promoting the growth and spread of breast cancer.

It’s important to note, however, that all breast cellsboth cancerous and noncanceroushave HER2 receptors other their surfaces. The difference is that;HER2-positive breast cancer cells have 40 to 100 times more receptors than HER2-negative breast cancer cells or normal breast cells. In positive cases, the abundance of receptors fuels the cancer.

Breast Cancer Discussion Guide

Get our printable guide for your next healthcare provider’s appointment to help you ask the right questions.

Options For Luminal Breast Cancer

Breast Cancer Subtypes

with luminal or other types of HR-positive breast cancer receive hormone therapy. Some people call this endocrine therapy.

Because triple-negative breast cancer is HR-negative, it does not respond to hormone therapy.

Anti-estrogen therapy

The four different types of anti-estrogen therapy are:

  • selective estrogen-receptor response modulators, such as Tamoxifen
  • aromatase inhibitors
  • estrogen-receptor downregulators, such as fulvestrant
  • luteinizing hormone releasing agents, including goserelin and leuprolide , prevent the ovaries from producing estrogen

The type of anti-estrogen therapy a person receives depends on various factors, including:

  • the stage of the breast cancer
  • whether the person has any other medical conditions
  • whether the person has been through menopause

A person usually continues hormone therapy for at least 5 years.

Other hormone therapies

In some cases, HR-positive breast cancer may not respond to the above treatments. If this is the case, a doctor may recommend one of the following hormone therapies for more advanced cancer:

  • progestin medications, such as megestrol
  • an anabolic steroid, such as fluoxymesterone

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When Is Her2 Testing Necessary

Anyone with a new diagnosis of invasive breast cancer should have HER2 testing. Its vital to have this information. It tells your doctor how the cancer is likely to behave and can guide treatment decisions. HER2 testing is a standard part of pathology testing for breast tumors.

You should also have HER2 testing if breast cancer spreads to other parts of the body or returns. This is necessary because it is possible for HER2 status to change. HER2-positive tumors can become negative and vice versa. Again, it is very important to know this for your treatment plan. Your doctor will take a new biopsy sample from the site where the cancer has spread or returned.

Are There Any Risks To The Test

You may have a little bruising or bleeding at the biopsy site. Sometimes the site gets infected. If that happens, you will be treated with antibiotics. A surgical biopsy may cause some additional pain and discomfort. Your health care provider may recommend or prescribe medicine to help you feel better.

There is very little risk to having a blood test. You may have slight pain or bruising at the spot where the needle was put in, but most symptoms go away quickly.

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Definitions And Molecular Features

It is important to clarify the relationship between triple-negative breast cancer and the basal-like phenotype. Triple-negative is a term based on clinical assays for ER, PR, and HER2, whereas basal-like is a molecular phenotype initially defined using cDNA microarrays. Although most triple-negative breast tumors do cluster within the basal-like subgroup, these terms are not synonymous; there is up to 30% discordance between the two groups. In this review we will use the term basal-like when microarray or more comprehensive immunohistochemical profiling methodology was used, and triple-negative when the salient studies relied on clinical assays for definition.

What Is Breast Cancer

Herceptin (trastuzumab) for HER2-Positive Breast and Stomach Cancer

Breast cancer is the abnormal growth of cells in the breast. These cells grow and develop into a cancerous growth that can have the potential to spread to other parts of the body.

It usually originates from the cells lining the milk ducts and glands. When it is detected at this non-invasive or in-situ stage, treatment is easier and patients have a higher chance of recovery.

However, when cancer cells invade the surrounding tissue, known as the stroma, it can gain entry into the circulatory and lymphatic system, and hence, to other organs in the body, through the blood and lymphatic vessels found in the stroma. And when these cancer cells reach a new site, they may form a metastatic tumour. The organs most commonly affected by this are the lungs, bones, and liver.

It is the most common cancer among Singaporean women. More than 25% of all cancers diagnosed in women are breast cancers and between 2011 and 2015, about 1927 women were diagnosed with it in Singapore each year.

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If I Have Chemotherapy Will I Need To Take Other Medications Like Trastuzumab

If your breast cancer is HER2-positive, its recommended that you take trastuzumab for one year, Dr. Abraham says. This ensures that the HER2 growth receptor on any remaining cancer cells stays shut off. Trastuzumab is not chemotherapy. The hair you lost during chemotherapy will regrow and your energy level will improve while youre taking trastuzumab.

Should I Enroll In A Clinical Trial

Clinical trials are definitely worth considering, according to the Susan G. Komen organization. They offer the chance to try and possibly benefit from new treatments. The best time to join a trial is before starting treatment or, if your provider is considering changing treatments, before you switch to a new treatment. Ask your doctor if there are any trials that would suit your circumstances. You can also search the clinical trial database at ClinicalTrials.gov or use the Susan G. Komen Metastatic Trial Search, a personalized tool to match you with clinical trials.

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New Guidelines On Treatment Of Her2

The American Society of Clinical Oncology recently released updated guidelines for the treatment of advanced HER2-negative breast cancer. The;Journal of Clinical Oncology;will publish the new guidelines, which include hormone therapy and sequential chemotherapy.

One of the ways breast cancers are classified is according to HER2 status, a measure of the amount of the HER2 protein found on the surface of the cancer cells. . In normal cells, HER2 helps to control cell growth. Cancer is considered HER2 positive when it has an abnormal amount of HER2, which can cause cells to grow more quickly and be more likely to spread to other parts of the body. Cancers that dont overexpress HER2 are considered HER2 negative.

The distinction between HER2-positive and HER2-negative breast cancer is important in treatment planning. There are drugs available for HER2-positive disease that specifically target the HER2 protein; HER2-targeted therapy, however, is not effective in HER2-negative breast cancer.

To describe current treatment options for HER2-negative breast cancer, ASCO recently released updated guidelines. An expert panel worked together to finalize the guidelines, which are based on a review of research from 1993 until now and focus on progression-free survival, response, quality of life, and side effects.


Journal of Clinical Oncology

Hormone Receptor Status And Prognosis


Hormone receptor status is;related to the risk of breast cancer recurrence.

Hormone receptor-positive tumors have a slightly lower risk of breast cancer recurrence than hormone receptor-negative tumors in the first;5 years after diagnosis .

After;5 years, this difference begins to decrease and over time, goes away .

For a summary of research studies on hormone receptor status and survival,;visit the Breast Cancer Research Studies section.;;

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What Happens During A Her2 Breast Cancer Test

Most HER2 testing involves taking a sample of tumor tissue in a procedure called a biopsy. There are three main types of biopsy procedures:

  • Fine needle aspiration biopsy, which uses a very thin needle to remove a sample of breast cells or fluid
  • Core needle biopsy, which uses a larger needle to remove a sample
  • Surgical biopsy, which removes a sample in a minor, outpatient procedure

Fine needle aspiration and core needle biopsies usually include the following steps:

  • You will lay on your side or sit on an exam table.
  • A health care provider will clean the biopsy site and inject it with an anesthetic so you won’t feel any pain during the procedure.
  • Once the area is numb, the provider will insert either a fine aspiration needle or core biopsy needle into the biopsy site and remove a sample of tissue or fluid.
  • You may feel a little pressure when the sample is withdrawn.
  • Pressure will be applied to the biopsy site until the bleeding stops.
  • Your provider will apply a sterile bandage at the biopsy site.

In a surgical biopsy, a surgeon will make a small cut in your skin to remove all or part of a breast lump. A surgical biopsy is sometimes done if the lump can’t be reached with a needle biopsy. Surgical biopsies usually include the following steps.

  • Once the biopsy area is numb or you are unconscious, the surgeon will make a small cut into the breast and remove part or all of a lump. Some tissue around the lump may also be removed.
  • The Overall Prognosis For Her

    Many studies demonstrate that breast cancers with an over-expression of HER-2 ;have a poorer prognosis. It is difficult however to isolate just the HER-2 aspect of the tumor as the specific cause of this poorer outlook.

    In addition, it is difficult, in general, to find practical indications of just what a; negative prognosis actually means.

    The HER-2 status is part of the picture, but so are:-

    • tumor size
    • grade
    • lymph node status
    • Other hormonal indicators
    • the type of cancer

    However, it is clear that a positive HER-2 over-expression does correspond to an increase in the likelihood for lymph node metastasis.

    HER-2 over-expression can also predict a poorer response to Taximophen , though researchers are working on ways to combat this.

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    What Are Breast Cancer Subtypes

    Breast cancer is complex, and not a one-size-fits-all disease. It can be broken down into different types based on an individuals unique diagnosis. Subtype is one factor of a diagnosis that helps explain what may be causing the cancer to grow.

    Currently, there are three main breast cancer subtypes:

    • Hormone receptor-positive is the most common subtype, accounting for 72 percent of all breast cancers. With this diagnosis, the cancer cells contain receptors for the hormones estrogen and/or progesterone. This means the cancer depends on one or both of these hormones to grow.1
    • Human epidermal growth factor receptor 2-positive indicates the cancer cells have an excess of HER2 protein causing the cancer to grow. About 15 percent of breast cancers are HER2-positive.2
    • Triple-negative breast cancer is the absence of hormone receptors and excess HER2 protein, and accounts for about 15 percent of breast cancers.1,2
    • These are example subtypes. A person could also have a combination of subtypes, and/or other factors contributing to cancer growth.

    Want to test what youve just learned? Take our Breast Cancer Quiz.

    What Is My Her2 Status

    Treatment Options for HER2-Negative Breast Cancer

    HER2 is another type of growth signal receptor which may be present on your breast cancer cells. About 25% of breast cancers are HER2-positive. HER2-positive cancers are a mix of good and bad news.;

    The bad news is the tumors tend to grow more aggressively than those without the HER2 receptor. The good news is that like ER/PR-positive cancers, medicines can switch the HER2 growth receptor off.;

    New drugs such as trastuzumab, pertuzumab, T-DM1 and lapatinib are extremely effective at this and have dramatically improved the prognosis for HER2-positive patients, Dr. Abraham says. Treatment outcomes are now as good as those with HER2-negative tumors.;

    But HER2-positive tumors bigger than half a centimeter or that have spread into the lymph nodes may require treatment with chemotherapy and one of the medicines specifically targeting the HER2 receptor, such as trastuzumab.

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    Where Do These Numbers Come From

    The American Cancer Society relies on information from the SEER* database, maintained by the National Cancer Institute , to provide survival statistics for different types of cancer.

    The SEER database tracks 5-year relative survival rates for breast cancer in the United States, based on how far the cancer has spread. The SEER database, however, does not group cancers by AJCC TNM stages; . Instead, it groups cancers into localized, regional, and distant stages:

    • Localized: There is no sign that the cancer has spread outside of the breast.
    • Regional: The cancer has spread outside the breast to nearby structures or lymph nodes.
    • Distant: The cancer has spread to distant parts of the body such as the lungs, liver or bones.

    The Following Statistics Are A Little Old Now They Are Much Better

    There are of course many factors that contribute to the survival of breast cancer.; However, some older studies show that only about 60%of patients with HER-2 positive status invasive breast cancer are disease free after 10 years.;

    In addition, about 65% survive overall .

    And, a greater number of HER-2 positive patients succumb to the illness during the first five years than those who are negative for HER-2 overexpression.

    At the same time, all other factors assumed to be equal, patients with negative HER-2 status tumors tend to be disease free at a rate of 75% over 10 years and have a slightly higher overall survival rate.

    From this, we can informally estimate that women with breast cancer which overexpresses HER-2 are about 10% more likely to have significant difficulties and ultimately succumb to the disease within the first five years, than those who do not. ;

    Because some of the Incidence and Prognosis rates are a little old now check out our brand new Index of Posts on Survival Rates.

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    What Is Triple

    Cell receptors are special proteins found inside and on the surface of cells. These receptor proteins are the eyes and ears of the cells, receiving messages from substances in the bloodstream and then telling the cells what to do.

    Hormone receptors inside and on the surface of healthy breast cells receive messages from the hormones estrogen and progesterone. The hormones attach to the receptors and provide instructions that help the cells continue to grow and function well. Most, but not all, breast cancer cells also have these hormone receptors. Roughly two of three breast cancers test positive for one or both of these hormone receptors.

    A smaller percentage of breast cancers about 20% make too much of the HER2 protein. In normal, healthy breast cells, the HER2 stimulates cell growth. When breast cancer cells have too much of the HER2 protein, however, the cells grow and divide too quickly.

    Hormonal therapies and HER2-targeted therapies disrupt the effects of estrogen, progesterone, and the HER2 protein on breast cancer, which can help slow or even stop the growth of breast cancer cells.

    Three common features of triple-negative breast cancer

    Who gets triple-negative breast cancer?

    Anyone can be diagnosed with triple-negative breast cancer. Still, researchers have found that it is more common in:

    If you are diagnosed with triple-negative breast cancer

    Its also important to remember there are therapies available that can treat triple-negative breast cancer.


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