S For Measuring Her2/neu
HER2 gene amplification is directly correlated with its mRNA expression and protein levels, and HER2 status can potentially be evaluated at any of these levels. A great number of commercially available testing kits are approved from FDA for the assessment of patients suitable for the treatment whit trastuzumab may be a suitable treatment. Overexpression of the HER2 protein product may be evaluated by Western blotting, ELISA or IHC; overexpression of its mRNA by Northern blotting or RT-PCR, and its gene amplification by fluorescence , chromogenic or silver-enhanced in situ hybridization .
FISH is more accurate, reproducible, and robust than IHC , but IHC has been more widely used as the primary test for HER2 status because it results quicker, is viewed using a conventional bright-field microscope, permits parallel viewing of tumor morphological features, and stained tissues do not degrade over time . Moreover, automated IHC techniques may enable more rapid testing.
The final IHC result is classified as 3+ in the case of a complete circumferential membrane staining in >10% of neoplastic cells, 2+ in the presence of moderate circumferential membrane staining of >10% of neoplastic cells, 1+ or 0 if there is incomplete membrane staining or no staining in >10% of neoplastic cells. A positive result includes the 3+ and the 2+ in the presence of a ISH confirmation .
What Are Breast Cancer Tumor Markers
Breast cancer tumor markers are substances, usually proteins or hormones, that are produced by the body in reaction to a tumor or by the tumor itself. They are found in the blood, urine or tissues or in the tumor tissue. Different markers indicate different stages of tumor progression and tumor growth, and they can be used to guide diagnosis and treatment and to predict prognosis.
The first stage of breast cancer detection is the mammogram, ultrasound or breast magnetic resonance imaging exam, all of which are sensitive enough to detect breast cancer before any symptoms are noticeable. If there are any suspicious signs, then a biopsy is carried out, and only then are tests for breast cancer tumor markers given. The tests are not sufficient by themselves, because the proteins and hormones that they detect are sometimes produced in the body by other conditions.
Do You Need Tests For Later
Imaging tests. If your cancer is stage IIIB or IV, you should get an imaging test to look for cancer in other parts of your body. Treatment can depend on how much and where the cancer has spread.
Tumor marker tests. If you have later-stage breast cancer, your doctor may also use blood tests to look at tumor markers. These tests should be done only when it is known that you have advanced cancer.
This report is for you to use when talking with your healthcare provider. It is not a substitute for medical advice and treatment. Use of this report is at your own risk.
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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.
Biology Of Hormone Receptors
The ER is a ligand-regulated, cytoplasmic receptor that belongs to the steroid nuclear receptor family, which in the ER-positive breast disease, promotes cell proliferation, survival, and invasion. The key components of ER are the DNA-binding domain, which binds with high affinity and specificity to estrogen response elements of DNA to regulate the transcription rates of target genes, and the ligand-binding domain, which binds estrogens . The binding of estrogen to its receptor is essential for its translocation into the nucleus, where it functions as a transcription factor and transduces hormonal signals into a large variety of physiological responses in various target organs.
Two forms of ER,
, Src kinase, Shc adaptor protein, and phosphatidylinositol 3-kinase , and the inhibition of TGF and tyrosine phosphatases . Finally, ER may also use calcium, cyclic adenosine monophosphate , and other second messengers for signal transduction.
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Is There Anything Else I Need To Know About Tumor Marker Tests
The information provided by tumor markers may be limited because:
- Some noncancerous conditions can cause tumor markers.
- Some people with cancer don’t have tumor markers.
- Not all types of cancer have tumor markers.
So, tumor markers are not usually used by themselves to diagnose or monitor cancer. But they can be useful when used along with other tests.
Is There Anything Else I Should Know
Laboratories may use different methods to test for CA 15-3, so results can vary from lab to lab. If you are having a series of CA 15-3 tests done, it is advised that you have the tests done by the same method, typically by the same laboratory, so that the results can be compared and interpreted correctly. You may wish to discuss this issue with your healthcare practitioner.
Levels of CA 15-3 are not usually measured immediately after breast cancer treatment begins. There have been instances of transient increases and decreases in CA 15-3 that do not correlate with the persons progress. Usually, the healthcare practitioner will wait a few weeks after starting treatment to begin monitoring CA 15-3 levels.
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List Of Blood Tests For Cancer Markers Commonly Used
Calcitonin is a hormone secreted by the parafollicular cells of the thyroid gland. Calcitonin can be used to detect thyroid cancer in early stages. S-100 is often raised in metastatic melanoma. S-100 can also monitor growth or regression of melanoma.
As it is quite evident from the above table that parameters to detect cancer markers are often not restricted to just the tumor or cancer, they are also elevated in plenty of non-cancerous conditions.
And that is why, tumor marker tests need to be done along with other blood tests, physical examination, CT/ MRI or PET scans, a detailed medical history and biopsies of suspected part having cancer are essential while making a definite diagnosis.
Medically Reviewed By
Dr. Himanshi is a Homoeopathic consultant and currently working as a lecturer in Post-graduate faculty of Homeopathy, Parul University, Vadodara. Completed BHMS and MD in Homeopathy in January 2018 and also has a clinical experience of about 6 years. Personal interests include reading, spending time with family and traveling.
What Are Estrogen And Progesterone Receptors
Receptors are proteins in or on cells that can attach to certain substances in the blood. Normal breast cells and some breast cancer cells have receptors that attach to the hormones estrogen and progesterone, and depend on these hormones to grow.
Breast cancer cells may have one, both, or none of these receptors.
- ER-positive: Breast cancers that have estrogen receptors are called ER-positive cancers.
- PR-positive: Breast cancers with progesterone receptors are called PR-positive cancers.
- Hormone receptor-positive: If the cancer cell has one or both of the receptors above, the term hormone-receptive positive breast cancer may be used.
- Hormone receptor-negative: If the cancer cell has neither the estrogen nor the progesterone receptor, it’s called hormone-receptor negative .
Keeping the hormones estrogen and progesterone from attaching to the receptors can help keep the cancer from growing and spreading. There are drugs that can be used to do this.
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Predicting Response To Therapy
As with prognostic factors, the available therapy-predictive markers in breast cancer, such as estrogen receptor, progesterone receptor, and HER-2 , all require tumor tissue for analysis. Preliminary findings, however, suggest that high serum HER-2 concentrations are associated with both poor response to endocrine therapy and cyclophosphamide-methotrexate-5-fluorouracilbased chemotherapy but can predict an improved response to a combination of trastuzumab and chemotherapy . These preliminary findings should now be confirmed in a large prospective trial.
CA 15-3 and other MUC-1related markers may also have a role in predicting response to therapy. Ren et al. recently reported that overexpression of MUC-1 in a mouse model system conferred resistance to cis-platinum. This resistance appeared to result from the ability of MUC-1 to inhibit apoptosis. Clearly, studies should now be carried out to determine whether either tumor tissue or serum concentrations of MUC-1related markers predict response/resistance in patients undergoing treatment with platinum-based therapies.
Can A Tumor Marker Be Used To Screen For Cancer
Ideally, markers could be used as a screening test for the general public. The goal of a screening test is to find cancer early, when it is the most treatable and before it has had a chance to grow and spread. So far, the only tumor marker to gain some approval as a screening tool is the Prostate Specific Antigen for prostate cancer, though this has concerns as well.
The main worry with tumor markers is that they are not specific enough they have too many false-positives. This means that the level is high when cancer is not present. This leads to costly tests that are not needed and causes the patient to be worried. The other concern is that the marker level is not high in early enough stages of the cancer, so the cancer cannot be found any earlier than when symptoms start to appear. Keep in mind that some substances used as tumor markers are normally made in the body, and a “normal” level is not always zero.
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Genomic Markers Prognosis And Personalized Treatment
In the past, breast cancers were simply treated based on some clinicopathological features, such as tumor size, lymph node status, patients age and menopausal status, and tumor biomarkers such as ER, PR, and HER2/neu. Then, systemic chemotherapy was applied nearly universally to locally advanced breast cancers regardless of their biomolecular profile, and to about 60% of early breast cancers, but often without any significant effect on women prognosis . As a consequence, a great debate has emerged about quality-of-life issues, acute and long-term side effects of systemic therapies, and the cost of unnecessary treatments . Therefore, in the last decades, quantitative approaches for prognosis prediction and treatment individualization have been developed, and genomic and molecular technologies are routinely applied to prevent overtreatments.
Recently, thanks to the increased level of knowledge regarding the molecular pathways and underlying genetic changes in breast cancer, the molecular signatures of gene expression have been correlated with breast cancer recurrence risk . Anyway, their current clinical application is still limited due to reproducibility questions and the need for fresh or frozen tissue.
Clinical Relevance Of Her2/neu
Having a look at the currrent literature, HER2 results amplified in approximately 1530% of breast cancers . HER2 overexpression, in the absence of adjuvant treatment, correlates with a poor prognosis in terms of both overall and disease-free survival, independent of tumor size, grade and hormone receptor status . However, HER2 is also an important predictive marker for responsiveness to HER2-targeted therapies, in both metastatic and adjuvant settings .
Trastuzumab, the most famous humanized monoclonal antibody against HER2, significantly improves response rates, time to progression and survival when used alone or added to chemotherapy in both early stage and metastatic breast cancer . Other HER2-targeted drugs, including the tyrosine kinase inhibitor lapatinib, the antibody pertuzumab, and the antibody drug conjugate adotrastuzumab emtansine , improve outcomes in HER2-positive metastatic breast cancer .
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How Is It Used
The cancer antigen 15-3 test and the related CA 27.29 test are mainly used to monitor response to breast cancer treatment and to help watch for breast cancer recurrence. They are used along with other clinical evaluations and tests, such as estrogen and progesterone receptors, Her2/neu, and gene expression tests for breast cancer , to evaluate a persons breast cancer.
CA 15-3 is sometimes ordered to provide a general sense of how much cancer may be present . CA 15-3 can only be used as a marker if the cancer is producing elevated amounts of it, so this test is not useful for all people with breast cancer.
The CA 15-3 and CA 27.29 tests are not sensitive or specific enough to use as a screening test for cancer because non-cancerous conditions can cause elevated levels.
Surveillance After Primary Treatment
Follow-up of patients after primary treatment for breast cancer with clinical examination, radiology, and biochemical testing is now standard practice in many centers. This practice is based on the assumption that the early detection of recurrent or metastatic disease enhances the chances of cure or survival. The evidence currently available, however, does not support this widely held assumption.
Two large multicenter randomized prospective trials compared outcome in patients followed up with clinical visits and mammography vs those who were followed up with an intensive regime that included radiology and traditional laboratory testing . Both studies concluded that use of an intensive follow-up program failed to improve outcome. Similarly, after pooling of the data from the above 2 studies, no significant difference in either disease-free interval or overall survival emerged between patients with intensive vs nonintensive surveillance .
Clearly, the available data do not support the use of an intensive follow-up program using standard biochemical testing and radiology after primary treatment for breast cancer. However, as pointed out by Emens and Davidson , the value of surveillance depends on both the sensitivity and specificity of the available diagnostic tests as well as the efficacy of therapy available for recurrent/metastatic disease.
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Does Every Cancer Type Have A Tumor Marker
There is not a known tumor marker for all types of cancer. Also, tumor markers are not raised in all cases of the cancers they are used for, so they are not helpful for all patients. For example, carcinoembryonic antigen is a tumor marker used in colon cancer, yet only 70-80% of colon cancers make CEA. This means 20-30% of people with colon cancer will not have a raised CEA level. Only 25% of early stage colon cancers have a raised CEA. Because of this, CEA cannot always help find colon cancer in its early stages, when cure rates are best.
The bottom line is, tumor markers can be very helpful in watching a person’s response to treatment and, in some cases, watching for the cancer to return. However, they need to be used along with your healthcare providers exam, any symptoms you are having, and radiology studies .
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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What Is Breast Cancer Staging
To determine the stage of your cancer, doctors look at how large your tumor is, where it is, and if it has spread. They also look at your medical history, physical exams, diagnostic tests, and tests of your tumor and lymph nodes.
- Early-stage breast cancer includes stages 0, I, II and IIIA .
- In stage 0, there are abnormal cells in the ducts or lobes of the breast. They have not broken through the wall of the duct or spread.
- In stages I, II, and IIIA, there is a tumor. It may have spread to lymph nodes under the arm, but it has not spread anywhere else.