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What Is The Fish Test For Breast Cancer

When It’s Done Types Of Tests And What Results Mean For You

Case 1: When to Use FISH Testing in Breast Cancer

Among the many things that will be done when you are being diagnosed with breast cancer is HER2 testing of your tumor. Human epidermal growth factor is a protein that, if present in high amounts, prompts a cancer to grow and metastasize more rapidly. It’s especially important to be aware if you are HER2-positive or HER-2 negative, as your status will dictate which treatments may be most effective for you.

What If A Carcinoma Is Infiltrating Or Invasive

These words are used to mean that the cancer is not a pre-cancer , but is a true cancer.

The normal breast is made of tiny tubes that end in a group of sacs . Cancer starts in the cells lining the ducts or lobules, when a normal cell becomes a carcinoma cell. As long as the carcinoma cells are still confined to the breast ducts or lobules, without breaking out and growing into surrounding tissue, it is considered in-situ carcinoma .

Once the carcinoma cells have grown and broken out of the ducts or lobules, it is called invasive or infiltrating carcinoma. In an invasive carcinoma, the tumor cells can spread to other parts of your body.

The Pathologist’s Assessment Of Biomarkers

Many factors influence the accuracy of detection of ER, PR, and HER-2 in the laboratory. These include pre-analytical factors , analytic factors , and post-analytic factors . Importantly, the results of these tests alone are the key determinants of what treatment is selected. The goal is to provide the right treatment to the right patient. The role of the pathologist is to accurately assess these biomarkers, which as indicated above is quite challenging and involved. The role of the oncologist is to treat the patient with one of several standardized therapies, such as endocrine therapy for ER/PR positive carcinomas, or trastuzumab for HER-2 positive carcinomas.

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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 5 years than in the first 5 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 5 year mark are much more likely to be “in the clear” and remain recurrence free.

Is Her2 Testing Safe

PhenoPath Adopts 2013 Updated ASCO

Both IHC and ISH testing are safe. In most cases, the testing will be done on tissue from your original biopsy and wont require that you have any additional procedures. Most biopsies can be completed in a doctors office or radiology room using local anesthetic.

Although a biopsy may be uncomfortable, its a very safe procedure with little risk. You may develop scar tissue around the biopsy site. You may also experience mild pain immediately following the biopsy. Talk with your doctor about the possible risks of a biopsy.

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Changes In Her2 Status

People often think of cancer cells as clones of one errant cell, but this is simply not the case. Cancer cells continue to develop new mutations and change. Different parts of a single tumor mass can have cancer cells with different characteristics , and these changes can become even more apparent when a tumor progresses, such as with a recurrence or metastatic disease.

It is not only HER2 status that can change. Estrogen receptor and progesterone receptor status may also change when a tumor recurs or metastasizes, and this change in receptor status is referred to as discordance. A tumor may change from being positive to negative for one of these receptors, or conversely, from being negative to positive.

The chance of discordance between the original tumor and a first or second metastasis is as follows:

PR 40.7 percent

In one 2016 study, almost 20 percent of tumors changed status from HER2-positive to HER2-negative, or vice versa. Knowing whether a tumor has changed is very important in selecting the best treatment options.

As long as the change is detected so that the best treatments can be recommended, it does not seem that a change in receptor status plays a large role in prognosis. In this study tumors which were discordant for HER2 had a similar prognosis to those tumors which did not change HER2 receptor status.

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 Does The Test Work

The testing lab typically uses a specialized staining process on the breast tissue sample to see if hormone receptors are present. The technical name for this procedure is an immunohistochemical staining assay or an ImmunoHistoChemistry . Findings will be included in a pathology report given to your doctor. ;If the cancer is deemed estrogen-receptor-positive , its cells have receptors for the estrogen hormone. That means that the cancer cells likely receive signals from estrogen to promote growth. About two out of every three breast cancers contain hormone receptors.

If the cancer is progesterone-receptor-positive , its cells have receptors for progesterone. This hormone could then promote the growth of the cancer.;

The cancer cells being estrogen and/or progesterone receptor-positive is a good prognostic factor to have, usually leading to a better prognosis.

What Do The Results Mean

HER2-positive breast cancer explanation video

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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Her2 Amplification Associated With Breast Cancer Fish Tissue

A predictive marker for patients with both node-positive or node-negative primary and metastatic breast cancer

Patients with HER2 amplification that may be candidates for therapies targeting the human epidermal growth factor receptor 2 protein

Confirming the presence of HER2 amplification in cases with 2+ or 3+ HER2 overexpression by immunohistochemistry, and for certain histologic subtypes with aberrant patterns of HER2 expression seen by immunohistochemistry

Fish For Breast Cancer


Figure 4: Representative view of potential breast carcinoma cells. HER2 signal is represented in red; centromere 17 probe can be used to enumerate chromosome number. HER2-non-amplified breast carcinoma: two centromeres 17 and two copy of the HER2 gene as expected. HER2-amplified breast carcinoma multiple detection for HER2.

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A Pathologist Makes A Diagnosis Of Cancer

The tissue from the biopsy is processed in the pathology lab, and the tissue is cut into thin sections and transferred to glass slides. Special dyes are applied to the glass slides that stain the tissues pink and blue so that the cells are visible under the microscope. Pathologists then look at the slides under a microscope to make a diagnosis of whether the tissue sample is benign or malignant .

What Is Vascular Lymphovascular Or Angiolymphatic Invasion What If My Report Mentions D2

Breast Cancer Tissue FISH Test

If cancer cells are seen in small blood vessels or lymph vessels under the microscope, it is called vascular, angiolymphatic, or lymphovascular invasion. When cancer is growing in these vessels, there is an increased risk that it has spread outside the breast. If your report does not mention this type of invasion, it means it is not there. Even if it is there, it does not always mean that your cancer has spread. How this finding affects your treatment is best discussed with your doctor.

D2-40 and CD34 are special tests that the pathologist may use to help identify these types of vascular invasion. These tests are not needed in every case.

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Case : When To Use Fish Testing In Breast Cancer

Ian Krop, MD, PhD: There was a time not long ago when there seemed to be discussion regarding the potential for false-negative IHC tests and the push to try to do the FISH test as the initial test to avoid false-negatives. My institution does the same thing that yours does. We do an IHC test on all patients and then do a FISH assessment only for equivocal cases. Did that point about doing upfront FISH testing kind of die out? Are there data about that? What do you think?

Evita Sadimin, MD: We actually did that at our institution for a certain period of time. We did FISH first, upfront, for everything, whatever the case. This was before the updated 2018 guidelines. So we were doing FISH first, and a significant number of cases fell into equivocal criteria. Now, with the most current 2018 guidelines, there is no equivocal criteria anymore, so it becomes more difficult if you start FISH first, at least for practical purposes in our institution.

Adam Brufsky, MD, PhD: It sounds like its a resource issue. Is it harder to do FISH than IHC, for your staff and everybody else?

Evita Sadimin, MD: We did that for about 3 years. We were OK resource-wise doing FISH first, but it just became impractical to do with the 2018 criteria.

Adam Brufsky, MD, PhD: Youd have to recount everything, and there were different nuclei and stuff. Is that why, with the new guideline?

Testing Algorithm Delineates Situations When Tests Are Added To The Initial Order This Includes Reflex And Additional Tests

Reflex testing will be performed using immunohistochemistry when the FISH result falls within certain ranges as defined by the 2018 focused update to the American Society of Clinical Oncology /College of American Pathologists guidelines. For FISH results in ASCO/CAP categories Group 2, 3, and 4 , the IHC testing will be added, charged, and reported separately. An integrated interpretation of the IHC and FISH results will be provided .

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Would This Testing Also Be Performed On A Man

Yes. Men do not get;breast cancer;as frequently as women, but it does occur and their cancer may also be;HER2-positive. Guidelines also recommend HER2 testing for clinical decision-making in patients of any gender with advanced stomach and esophagus cancers who are potential candidates for HER2-targeted therapy.

What Does It Mean If My Carcinoma Has Tubular Mucinous Cribriform Or Micropapillary Features

HER2 Testing in Metastatic Breast Cancer

These are different types of invasive ductal carcinoma;that can be identified under the microscope.

  • Tubular, mucinous, and cribriform carcinomas are “special types” of well-differentiated cancers that often have a better prognosis than the more common type of invasive ductal carcinoma .
  • Micropapillary carcinoma is a type of invasive breast carcinoma that often has a worse prognosis.

If your doctor knows that your tumor is made up of one of these special types of breast cancer, he or she may recommend different treatment.

Since some tumors are made up of more than one type, the entire tumor must be removed in order to know what types your tumor contains. A needle biopsy doesnt give enough information to guide treatment.

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Guidelines For Interpretation Of Her2 Immunohistochemistry

20012004: The FDA approved DAKO guidelines were used for scoring as follows: 0 , 1+ , 2+ or 3+ . During this period, HER2 IHC was assessed by all board certified staff members .

20112012: The ASCO-CAP guidelines were used for the interpretation of staining and HER2 protein expression was scored as 0 , 1+ , 2+ or 3+ .

During this period, the vast majority of HER2 IHC was assessed by three breast pathologists.

After Treatment Maintain A Healthy Weight

Obese women have higher levels of estrogen circulating in their bodies than women who are in their ideal body weight range.

Many studies including a study conducted by researchers from the Iranian Institute for Health Sciences Research in Tehran, Iran, have demonstrated an association between body mass size and breast cancer in post-menopausal women.

If youre overweight, Taylor recommends losing weight through a healthy diet and regular exercise once youve finished treatment. Weight loss during treatment isnt typically encouraged, as this is often associated with undesired muscle loss, leading to fatigue, a suppressed immune system and a slower healing process.

Allow your body the nutrients it needs to fight cancer, she says. Once your treatment is done, consider meeting with a dietitian for individualized recommendations to decrease recurrence risk and support a healthy weight.

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Guidelines For Interpretation Of In Situ Hybridization

20012007: The FISH signals were interpreted in accordance with the FDA guidelines as follows: the number of signal copies and the ratios were calculated for each probe. Gene copies or cluster formations were defined as amplified. Ratios were defined as follows: ratio>2.0 was set as amplified status; a ratio2.0 was negative .

20082012: The ASCO-CAP guidelines were used for interpreting the signals in the FISH tests. Similarly to the previous period, the number of signal copies and the ratios were calculated for each probe Gene copies or cluster formations were defined as amplified. Similarly, a ratio>2.2 was set as amplified status; a ratio<1.8 was negative, and a ratio of 1.8 – 2.2 was referred to as equivocal .

During the whole analyzed period , FISH HER2 diagnostic service was covered by two board certified pathologists at the same time , who acquired thorough expertise in HER2 FISH assay interpretation.

The presence of aneusomy of chromosome 17 was documented in the histology reports during the whole analyzed period .

What If My Report Mentions Micrometastases In A Lymph Node

Webcast: HER2 ASCO/CAP Update â Clinically

This means that there are cancer cells in the lymph nodes that are bigger than isolated tumor cells but smaller than regular cancer deposits. If micrometastases are present, the N category is described as pN1mi. This can affect the stage of your cancer, so it might change what treatments you may need. Talk to your doctor about what this finding may mean to you.

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What If My Report Mentions Her2/neu Or Her2

Some breast cancers have too much of a growth-promoting protein called HER2/neu . The HER2/neu gene instructs the cells to make this protein. Tumors with increased levels of HER2/neu are referred to as HER2-positive.

The cells in HER2-positive breast cancers have too many copies of the HER2/neu gene, resulting in greater than normal amounts of the HER2 protein. These cancers tend to grow and spread more quickly than other breast cancers.

All newly diagnosed breast cancers should be tested for HER2, because women with HER2-positive cancers are much more likely to benefit from treatment with drugs that target the HER2 protein, such as trastuzumab , lapatinib , pertuzumab , and T-DM1 .

Testing of the biopsy or surgery sample is usually done in 1 of 2 ways:

  • Immunohistochemistry : In this test, special antibodies that will stick to the HER2 protein are applied to the sample, which cause cells to change color if many copies are present. This color change can be seen under a microscope. The test results are reported as 0, 1+, 2+, or 3+.
  • Fluorescent in situ hybridization : This test uses fluorescent pieces of DNA that specifically stick to copies of the HER2/neu gene in cells, which can then be counted under a special microscope.

Many breast cancer specialists think that the FISH test is more accurate than IHC. However, it is more expensive and takes longer to get the results. Often the IHC test is used first:


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