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What Is Her2 Neu Negative Breast Cancer

Will I Need Radiation

Updates on hormone receptor-positive HER2-negative breast cancer

Most oncologists generally recommend radiation treatment for all breast cancer patients who undergo only removal of the tumor .

For women who undergo whole-breast removal, radiation may be recommended for those who are considered high-risk, especially those with tumors larger than 5 centimeters and with more than four cancerous lymph nodes.

C Future Therapies For Triple Negative Breast Cancer

Targeted agents that have been / are being investigated in the treatment of metastatic TNBC include inhibitors of poly polymerase, angiogenesis, mammalian target of rapamycin, epidermal growth factor receptor, HDAC, and Src. Several of these agents have shown some benefit in pre-clinical trials . EGFR inhibitors in particular have shown promise in clinical trials in a subset of patients with the addition of either carboplatin or cisplatin . Indeed, multiple EGFR antibodies and small molecule inhibitors are currently in phase II trials. Unfortunately, a disappointing 20% of patients have so far been shown to benefit from EGFR inhibition, but this therapy may be beneficial to some patients.

Inhibitors of Src and PARP have generally not shown a distinct survival benefit as single agents for patients with TNBC . Inhibitors for c-MET, androgen receptor, mTOR, PARP and EGFR either as single agents or in combination with other therapies have shown pre-clinical and/or early clinical promise and are currently undergoing clinical trials as either adjuvant or neoadjuvant therapies .

What Do The Results Mean

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.

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B Current Therapies For Erbb2/her2 Overexpressing Breast Cancers

The current therapeutic approach for HER2-positive early-stage and metastatic breast cancer is a combination of HER2-targeted monoclonal antibody treatment concurrent with chemotherapy .

The mechanism of action for Trastuzumab has not been completely established, but is perceived to be through both innate and adaptive immunities . Innate mechanisms lead to cell cycle arrest and adaptive mechanisms involve antibody-dependent cell-mediated cytotoxicity . Alone, Trastuzumab does not seem to promote a significant level of cell death, but the synergistic outcome with chemotherapy results in the inhibition of the cell survival promoting PI3K/Akt signaling pathway . Additionally, the small molecule dual inhibitor of EGFR/ERBB2 receptors, Lapatinib, is also FDA-approved as a combination treatment with Capecitabine for HER2-positive advanced breast cancer that has progressed after previous treatment with other chemotherapeutic agents or combination therapies . Lapatinib exerts anti-proliferative effects via the inhibition of tyrosine kinase phosphorylation, which decreases the signaling capabilities of the PI3K/Akt and MAPK pathways .

How Her2 Status Affects Treatment

Figure 4 from HER2

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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What Is The Risk For Triple

The disease can affect anyone, but is more likely to show up in those who are:

  • Younger than age 50 .
  • Black or Latinx.
  • Living with a genetic condition called BRCA mutation that increases the risk for breast cancer and other forms of cancer. Most cancers diagnosed in people with the BRCA1 mutation are triple negative.

Options For Luminal Breast Cancer

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

Triple-negative breast cancer does not respond to hormone therapy because it is HR-negative.

Anti-estrogen therapy

Anti-estrogen therapy works by preventing estrogen from attaching to the estrogen receptors of breast cancer cells.

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 .

Other hormone therapies

In some cases, HR-positive breast cancer may not respond to the above treatments. Consequently, 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

Targeted therapies

Targeted therapies focus on specific genetic mutations that play a role in a cancers growth and spread. These drugs are usually combined with hormone therapy.

Examples of CDK4/6 inhibitors include:

  • abemaciclib
  • palbociclib
  • ribociclib

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The Overall Hormone Receptor Status Of A Breast Tumor Helps Predict Behaviour And Responsiveness To Treatment

Indeed, specialists consider the hormone-receptor status of a tumor to be more of a predictive factor rather than a prognostic factor. It helps determine what you are up against, and how best to treat it.

However, research shows that the outlook for a particular breast cancer is more likely to be influenced by the histological type and grade of the breast cancer tumor at the time of discovery.

Also, whether or not there is lymphatic involvement is another important factor, and not the hormone receptor status.

It is true, however, that breast cancer tumors with a positive hormone receptor status have a more indolent course than do hormone receptor-negative tumors.

Indolent is kind of a strange term to use, but it means that a tumor is less responsive or lazy in response to treatment than hormone negative receptor status tumors. Some kind of extra intervention or boost is often necessary to really get a positive healing response from cancer.

However, the good news is that certain kinds of hormone-receptor-positive tumors are actually more responsive to endocrine therapy. So, there is a positive aspect to this as well.

In fact, there is often a kind of inverse relationship between the HER-2 hormone receptor status, and the ER and PR status of a tumor.

Many Women With Early

Olaparib Beneficial for BRCA-Mutated HER2-Negative Breast Cancer

It turns out that many women with early stage breast cancer dont need chemotherapy. The recent study called the TAILORx trial found that thousands of women with a certain type of early-stage hormone-positive, HER-2 negative breast cancer did just as well with hormone therapy alone. These results will be practice-changing, said Kristen D. Whitaker, MD, a clinical cancer geneticist specializing in breast cancer at Fox Chase Cancer Center.

About 1 in 8 women in the US get invasive breast cancer. Half of these cancers are due to estrogen-sensitive tumors that test negative for the HER2 protein, a protein that promotes the growth of cancer cells.

Breast cancers that test positive for HER2 tend to be more aggressive than other types of breast cancer and are less responsive to hormone therapy alone, which is why patients with this disease are usually treated with a combination of chemotherapy and hormone therapy.

But, patients with cancers that test negative for HER2, have a lower risk of cancer recurrence, and have estrogen-positive cancer in an early stage that hasnt spread to the lymph nodes, may be able to skip chemotherapy and just take hormone therapy alone.

The TAILORx trial found that chemotherapy can be avoided in about 70 percent of women with estrogen sensitive, HER2-negative, lymph node-negative breast cancer, Whitaker said. This is exciting because we now have data to better tailor treatments.

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Her2 In Gastric Cancer

HER2 overexpression in patients with gastric cancer has been reported from 10 to 30% and correlates with poor outcome and a more aggressive disease. Overexpression of HER2 protein in gastric cancer, using immunohistochemistry , was first described in 1986 . In a study by Yano et al. , HER2 overexpression by IHC was found in 23% and gene amplification by FISH in 27% of 200 resected tumors. Gravalos and Jimeno in their study of 166 gastric cancer patients observed that HER2 overexpression was most commonly found in gastroesophageal junction tumors and tumors having intestinal type histology. Other studies also confirmed a higher rate of HER2 positivity in GEJ tumors and intestinal subtype . HER2 overexpression is directly correlated with poorer outcome in gastric cancer. In a study of 260 gastric cancers, HER2 overexpression was an independent negative prognostic factor and HER2 staining intensity was correlated with tumor size, serosal invasion, and lymph node metastases . Other studies also confirmed the negative impact of HER2 overexpression in gastric cancer .

How Big Is My Tumor

Tumor size is another factor that will determine your course of treatment. Your doctor uses the size of your tumor to stage, or further categorize your cancer .

The tumors dimensions are estimated by a physical exam, a mammogram, an ultrasound or an MRI of the breast. The precise size wont be known until a pathologist studies the tumor after surgical removal.

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There Are Two Ways To Measure The Her

The most common way to measure the HER-2 status of a potential breast cancer tumor is through an immunohistochemistry test. This will likely be part of an overall histological/pathological evaluation of the tumor.

Various tumor markers, including the HER-2 status indicators, give the pathologist a characterization of the tumor. This helps to predict the future behavior and probable responses, of the tumor to different types of treatments.

The immunohistochemistry test of the HER-2 status measures the over-expression of a particular protein and is typically given a score of 0 to +3.

The pathologist actually counts the number of receptors on the surface of the cancer cells. Indeed, the pathologist can see the cells microscopically because they are receptive to certain protein-based dyes and change color.

Scores of 0 and +1 are indicative of a negative status , whilst +2 and +3 are HER-2 positive . There is no in-between state.

How Does Her2 Positive Breast Cancer Develop

Systemic treatment landscape and algorithm for hormone

While we are still learning about the causes of HER2 positive breast cancer, researchers have identified how HER2 positive breast cancer develops. In about 25 percent of breast cancers, the cancer cells have an excess of the HER2 protein. This is caused by a mutation in the HER2 gene. When the HER2 gene mutates, it causes cells in the breast to grow and divide at an uncontrolled rate, leading to tumor growth.

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Hormone Receptor Status And Early Breast Cancer 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 about 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.

The 2013 Asco/cap Her2 Testing Guidelines

  • Always test HER2 status on newly diagnosed, invasive breast cancers .
  • Ensure that at least one tumor sample is tested for either HER2 protein expression or for HER2 gene amplification.
  • Discuss the role of HER2-targeted therapy if the HER2 test result is positive and if there is no apparent histopathologic discordance with HER2 testing.Delay the decision to recommend HER2-targeted therapy if the HER2 test result is equivocal.
  • Mandatory re-testing should be done on the same specimen, using the alternative test if the initial HER2 test result is equivocal, or on an alternative specimen.
  • Do not administer HER2-targeted therapy if the HER2 test result is negative. If there is apparent histopathologic discordance with the HER2 test result, additional HER2 testing should be considered.
  • Report a HER2 test result as indeterminate if technical issues prevent one or both tests from being done in a tumor specimen, or prevent the test from being reported as positive, negative, or equivocal.
  • Confirm that the testing laboratory conforms to standards set for accreditation by CAP or an equivalent accreditation authority.
  • In rare cases, it may be difficult to know for sure if the result is positive or negative. If additional testing on other tissue specimens is not possible, pathologists and oncologists should consider all available clinical data on the patient prior to recommending HER2-targeted therapy.

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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.

The Switch Of Breast Tumours To Her2

Treatments for HR , HER2-Negative Metastatic Breast Cancer

LUGANO, Switzerland – The finding that breast tumours can evolve to express low HER2 potentially widens the number of patients who can benefit from new investigational agents, typically novel antibody-drug conjugate therapies, that are currently in clinical trials for HER2-low tumours.

The first study of its kind exploring how breast cancers change from the primary to the recurrent tumour has revealed that nearly 30% of breast cancer patients convert from, or to, human epidermal growth factor receptor 2-low status. Specifically, the study found that 14% of triple-negative breast cancers with HER2-negative expression in the primary tumour converted to HER2-low expression in the recurrent tumour possibly offering an option to such hard-to-treat tumours.

Traditionally, breast cancers are categorised as: hormone receptor positive /HER 2-negative, , HER2-positive, or triple negative . HER2-low refers to HER2-negative tumours with low HER2 biomarker expression. About half of breast cancers classified as HER2-negative show low HER2 expression.

In total, 29% of recurrent breast cancer biopsies showed conversion either from, or to, HER2-low expression. In primary tumours and relapse tumours, HER2-low expression was seen in 34% and 38% of tumours, respectively. A total of 15% HER2-negative tumours switched to HER2-low tumours, and 14% HER2-low switched to HER2-negative.

Notes to Editors

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References

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Risk Of Recurrence: Early And Late

Research has shown the HER2-positive early breast cancers are two to five times more likely to recur than HER2-negative tumors. Even very small HER2-positive tumors with negative lymph nodes have a much higher risk of recurrence relative to tumors that are HER2-negative. Treatment with Herceptin can cut this risk by half.

The pattern of breast cancer recurrence may also differ. Small tumors are also more likely to have a metastatic recurrence if they are HER2-positive.

Despite the fact that HER2-positive and estrogen receptor-negative tuors are more likely to recur early on than estrogen receptor-positive and HER2-negative cancers, late recurrences are much less common.

With estrogen receptor positive breast cancers, the cancer is more likely to recur after five years than in the first five years, and the risk of recurrence remains steady each year for at least 20 years following the diagnosis. In contrast, those who have HER2 positive tumors and reach their five-year mark are much more likely to be “in the clear” and remain recurrence free.

B Current Standard Of Care For Triple Negative Breast Cancer

Triple negative breast cancers are unique in the sense that many of the most effective second-line therapies target the estrogen or the HER2 receptors, which are not present in this disease. Treatment options are limited and recurrent tumors often develop resistance to current standard therapies such as anthracyclines or taxanes. Although the mitotic inhibitor Eribulin has shown some survival benefit in metastatic TNBC patients , median increase in survival was only 1.5 months, which is far from ideal. The anti-microtubule agent Ibexapilone has also recently been approved for the treatment of metastatic breast cancer and has induced a significantly longer progression-free survival time when combined with capecitabine than capecitabine alone . Despite these advances, cytotoxic chemotherapy and DNA damaging agents continue to be the most frequently used for treatment of TNBC .

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