What Is Her2 Negative Breast Cancer

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.

How Is Tnbc Diagnosed

Imaging tests are usually the first tests done:

• Mammography, the most common screening tool for breast cancer, uses X-rays to take images of the breast and can uncover tumors that may be too small to feel.
• MRI uses a magnet, radio waves and a computer to make detailed images of the breast with a much greater resolution than a mammogram offers.

The next step is a biopsy to remove a sample of suspicious cells from the breast to analyze them. Techniques include:

• Surgical biopsy

The appropriate type of biopsy for you depends on factors such as the size and location of the tumor. You may also have a biopsy of your underarm lymph nodes at the same time to see if any cancer is there.

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.

Its 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

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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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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 .

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Generation And Characterization Of Trastuzumab

First, we generated trastuzumab-resistant clones by chronically exposing the HER2 amplified breast cancer cell line BT474 to increasing concentrations of trastuzumab for over 18 mo in vitro. BT474 cell clones resistant to the antiproliferative effects of trastuzumab were identified. As shown in , the proliferation of a representative BT474 trastuzumab-resistant cell line is undisturbed in the presence of increasing concentrations of trastuzumab. An emerging body of evidence suggests that cells cultured in monolayer may respond differently to trastuzumab than cells grown in 3D cultures . Thus, we tested the capacity of our resistant cells to form tumors in the presence of trastuzumab. To do this testing, we orthotopically injected in vitro resistant clones in immunodeficient mice and treated the animals twice weekly with trastuzumab . Where appropriate, we show results from one representative in vitro and in vivo trastuzumab-resistant cell line, referred to from here on as BT474R and BT474R2, respectively .

Life Expectancy And Outlook

In the United States, its estimated that more than 42,000 women will die from breast cancer in 2020.

However, its important to know that aspects like life expectancy and your outlook can vary greatly based off many individual factors.

In the past, a diagnosis with HER2-positive breast cancer was associated with a poor outlook. Advances in drug therapies in recent years have improved the treatment options for HER2-positive breast cancer as well as the outlook for people with the disease.

According to the American Cancer Society, HER2-positive breast cancers are much more likely to respond to drugs that target the HER2 protein, despite the fact that they can grow and spread quickly.

This type of treatment is called targeted therapy. Well discuss it in more detail in a bit.

When considering your outlook, your doctor must analyze many other factors as well. Among them are:

Hormone treatments may be an option for cancer thats also HR positive.

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Testing For Her2 Status

There are several tests used to find out if breast cancer is HER2-positive. How your results appear in the report will depend on the test you have. Two of the most common tests are:

• IHC test : The IHC test uses a chemical dye to stain the HER2 proteins. The IHC gives a score of 0 to 3+ that measures the amount of HER2 proteins on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+, its considered HER2-negative. If the score is 2+, it’s considered borderline. A score of 3+ is considered HER2-positive. If the IHC test results are borderline, its likely that a FISH test will be done on a sample of the cancer tissue to determine if the cancer is HER2-positive.
• FISH test : The FISH test uses special labels that attach to the HER2 proteins. The special labels have chemicals added to them so they change color and glow in the dark when they attach to the HER2 proteins. This test is the most accurate, but it is more expensive and takes longer to return results. This is why an IHC test is usually the first test done to see if a cancer is HER2-positive. With the FISH test, you get a score of either positive or negative .

It’s important to know which HER2 test you had. Generally, only cancers that test IHC 3+ or FISH positive respond to the medicines that target HER2-positive breast cancers. An IHC 2+ test result is called borderline. If you have an IHC 2+ result, ask to have the tissue retested with the FISH test.

Why Is Knowing Hormone Receptor Status Important

Knowing the hormone receptor status of your cancer helps doctors decide how to treat it. If your cancer has one or both of these hormone receptors, hormone therapy drugs can be used to either lower estrogen levels or stop estrogen from acting on breast cancer cells. This kind of treatment is helpful for hormone receptor-positive breast cancers, but it doesnt work on tumors that are hormone receptor-negative .

All invasive breast cancers should be tested for both of these hormone receptors either on the biopsy sample or when the tumor is removed with surgery. About 2 of 3 breast cancers have at least one of these receptors. This percentage is higher in older women than in younger women. DCIS should be checked for hormone receptors, too.

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What Is My Her2 Status

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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Outcomes According To Hr Status

When HR was positive, the HER2 group and HER2+ + T group had significantly lower LRR , DM and higher DFS at 5 years than that in the HER2+ T group. There were no significant differences in LRR , DM or DFS at 5 years between the HER2 group and HER2+ + T group.

Figure 3 KaplanMeier plots of locoregional recurrence , distant metastasis , disease-free survival , and overall survival of HR-positive patients and HR-negative patients grouped according to HER2 status and trastuzumab treatment. HR, hormonal receptor-negative HR+, hormonal receptor-positive HER2, HER2-negative HER2+ + T, HER2-positive with trastuzumab HER2+ T, HER2-positive without trastuzumab.

When HR was negative, there were no significant differences in LRR, DM, DFS or OS among HER, HER2+ + T, or HER2+ T groups .

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What Do The Hormone Receptor Test Results Mean

A test called an immunohistochemistry is used most often to find out if cancer cells have estrogen and progesterone receptors. The test results will help guide you and your cancer care team in making the best treatment decisions.

Test results will give you your hormone receptor status. It will say a tumor is hormone receptor-positive if at least 1% of the cells tested have estrogen and/or progesterone receptors. Otherwise the test will say the tumor is hormone receptor-negative.

Hormone receptor-positive breast cancer cells have either estrogen or progesterone receptors or both. These breast cancers can be treated with hormone therapy drugs that lower estrogen levels or block estrogen receptors. Hormone receptor-positive cancers tend to grow more slowly than those that are hormone receptor-negative. Women with hormone receptor-positive cancers tend to have a better outlook in the short-term, but these cancers can sometimes come back many years after treatment.

Hormone receptor-negative breast cancers have neither estrogen nor progesterone receptors. Treatment with hormone therapy drugs is not helpful for these cancers. These cancers tend to grow faster than hormone receptor-positive cancers. If they come back after treatment, its often in the first few years. Hormone receptor-negative cancers are more common in women who have not yet gone through menopause.

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.

References:

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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.

How Her2 Status Affects Treatment

For more than 30 years, researchers have been studying HER2-positive breast cancer and ways to treat it.

Targeted therapies have now changed the outlook of stage 1, 2, and 3 breast cancers from poor to good.

While targeted therapies are part of the standard treatment for HER2-positive breast cancer, theyre only used occasionally in HER2-negative breast cancer.

Another difference between HER2-positive treatments and HER2-negative treatments is that HER2-negative treatments are often oral medications. HER2-positive treatments are usually administered intravenously or by injection.

For HER2-positive or HER2-negative breast cancers that are estrogen-positive or progesterone-positive, treatment with hormonal therapy may also be recommended.

Medications that may be used to treat HER2-negative breast cancers that are hormone-negative include:

• sacituzumab govitecan , an IV treatment
• talazoparib

Medications that may be used to treat HER2-negative breast cancers that are hormone-positive include:

• abemaciclib
• palbociclib
• ribociclib

Some of these medications are taken on their own, while others must be administered with other medications. Factors that affect your treatment regimen include whether:

• youve gone through menopause
• youve already received hormone therapy or chemotherapy
• you have certain gene mutations

Trastuzumab is a biologic therapy thats administered intravenously.

Other treatments for HER2-positive breast cancer include:

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How Is This Cancer Treated

Your treatment plan will depend on where the cancer has spread, the extent of the disease, other medical conditions you have, and your age and menopause status. Common therapies include:

• Ovarian suppression For premenopausal women with metastatic breast cancer of this type, hormone therapy almost always begins with ovarian suppression by means of surgery to remove the ovaries or drugs, such as goserelin or leuprolide, that stop the ovaries from producing hormones, says Brufsky. Ovarian suppression lowers hormone levels in the body so the tumor cant get the estrogen it needs to grow.
• Aromatase inhibitors Postmenopausal women and premenopausal women who have undergone removal or suppression of their ovaries are often treated with AIs, such as anastrozole, exemestane, and letrozole. These drugs block the activity of the enzyme aromatase, which the body uses to make estrogen in the adrenal glands and fat tissue. This means less estrogen is available to stimulate the growth of HR-positive breast cancer cells, according to the National Cancer Institute.
• CDK4/6 inhibitors These drugs, which include palbociclib, ribociclib, and abemaciclib, block proteins in the cell known as cyclin-dependent kinases . CDKs regulate cell proliferation and growth and are often elevated in breast cancer, fueling uncontrolled growth of cancer cells. They are typically used in combination with AIs as a first-line treatment for HR-positive/HER-2-negative metastatic breast cancer, Brufsky says.

Monotherapy Vs Combination Therapy

Three trials have been conducted to compare monotherapy and combination therapy. The FACT trial demonstrated that the combination of a selective ER degrader and an AI was not superior to an AI alone. However, the SWOG trial thereafter did show superiority. Moreover, the SoFEA trial substantiated the results of the initial FACT trial, showing no real difference between combination therapy and monotherapy.

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What Are The Symptoms Of Her2 Breast Cancer

The most common symptom of most breast cancers, including HER2 breast cancer is a lump in the breast. A painless, hard mass with irregular edges is most likely cancer, but breast cancers can also have a lump that is soft and tender to the touch. Other possible symptoms in the first three stages of breast cancer include:

• Change in the size and shape of the breast

• Jaundice and stomach swelling

Determining Your Her2 Status

A breast biopsy is used to determine HER2 status. The biopsy can be sent for laboratory testing with an immunohistochemistry test. The fluorescence in situ hybridization test looks for the HER2 gene in breast cancer cells.

The results of an immunohistochemistry test show different levels of HER2 positivity. For example, a tumor may be reported as 0, 1+, 2+, or 3+. Tumors with a higher number may be referred to as having an overexpression of HER2.

According to the American Cancer Society, immunohistochemistry test results should be considered as follows:

The impact of being HER2-positive on breast cancer survival is, of course, a top concern. Unfortunately, statistics can be misleading without considering other aspects of your diagnosis, including cancer stage at diagnosis and whether the tumor is also estrogen and/or progesterone receptor-positive.

With this in mind, you may also be tested for progesterone and estrogen receptors. Triple-negative breast cancers are negative for HER2, estrogen, and progesterone, while triple-positive breast cancers are positive for all three.

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