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Breast Cancer Tumor Markers Prognosis

Does Every Cancer Type Have A Tumor Marker

CA 15-3 test | Breast cancer diagnosis | tumor marker (Everything you need to know)

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 high CEA level. Only 25% of early stage colon cancers have a higher than normal CEA. Because of this, CEA cannot always help find colon cancer in its early stages, when cure rates are best.

Tumor markers can be very helpful in watching your 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 .

Possible Side Effects Of External Beam Radiation

The main short-term side effects of external beam radiation therapy to the breast are:

  • Swelling in the breast
  • Skin changes in the treated area similar to a sunburn

Your health care team may advise you to avoid exposing the treated skin to the sun because it could make the skin changes worse. Most skin changes get better within a few months. Changes to the breast tissue usually go away in 6 to 12 months, but it can take longer.

External beam radiation therapy can also cause side effects later on:

Peptide Extraction For Lc

To extract tissues for LC-MALDI peptide analysis, slides were subjected to antigen retrieval and vacuum dried for 1 h, then the tissue was removed from the slide, placed in a 1.5 mL tube in 500 l of 0.2% RapiGest SF surfactant in 50 mM ABC, vortexed, sonicated 10 min, then trisphosphine was added to a final concentration of 5 mM. Samples were heated for 30 min at 60°C, cooled to room temperature, and alkylated with 15 mM iodoacetamide for 30 min in the dark. BCA assays were performed to determine protein concentrations. Trypsin was added at 1 g per 50 g protein, and incubated overnight at 37°C. TFA was added to the digested protein samples to a concentration of 0.5% and incubated at 37°C for 40 min. Samples were centrifuged at 13,200 rpm for 10 min, and supernatants were collected and freeze-dried. Samples were reconstituted with 2% ACN/0.1% TFA, centrifuged at 13,200 rpm , and supernatants were passed through a 0.2 m filter into HPLC vials.

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When You Need Themand When You Dont

When you learn that you have breast cancer, its normal to want to do everything you can to treat it and be sure it doesnt come back. But its not always a good idea to get all the tests that are available. You may not need them. And the risks may be greater than the benefits.

The information below explains when cancer experts recommend imaging tests and tumor marker testsand when they dont.

Imaging tests, such as CT, PET, and bone scans, take pictures to help find out if the cancer has spread in your body. Another test, called a tumor marker test, is a kind of blood test. Tumor markers are also called biomarkers or serum markers. They are higher than normal in some cancer patients. The tests you need depends on the stage of your breast cancer.

What Are Tumor Markers Used For

Prognostic markers on Breast Cancer

Tumor markers are most often used to track how your cancer is responding to treatment. If the level is going down, the treatment is working. If it goes up, the cancer may be growing. There are health issues other than cancer that can cause markers to be higher. Because of this, you must think about the tumor marker levels along with the results of radiology scans , your symptoms, and your healthcare providers exam.

In some cancers, markers are used to watch for recurrence . This is not useful in all cancer types. In breast cancer, research has found that watching tumor markers after treatment does not help people live longer. For that reason, they are not recommended.

Tumor markers can also be used along with other tests to help find cancer if you have symptoms that could be caused by cancer. Some markers can help predict how you will do and guide your treatment plan.

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Prognostic Multigene Classifiers In Clinical Practice

These types of assays are mostly based on quantitative analysis of messenger RNAs extracted from archival paraffin sections. The protocol includes reference genes that enable normalization of the data and result in significant improvement in the stability. The assays typically categorize patients into groups primarily based on prognosis, although they may also have utility in predicting likelihood of response to chemo or endocrine therapies. Thus patients who are going to get maximal benefit from hormonal therapy can be spared from taking toxic chemotherapies for little or no gain. The assays can be integrated with pathological and clinical information to increase their performance.

A number of multigene prognostic classifiers have now been described. These include the 21-gene assay , Mammaprint and Blueprint gene tests28 , the Breast Cancer Index ,29 and the PAM50-based Prosigna assay.2,30,31

The Oncotype Dx assay assesses 21 genes and provides a continuous score that predicts the risk of recurrence. This test is recommended in a number of national guidelines for guiding treatment of women with newly diagnosed stage I or II, ER-positive breast cancer. This assay also routinely provides quantitative mRNA levels for ER, PR, and HER2.

The 80-gene BluePrint assay identifies the molecular subtype and predicts tumor response to targeted therapies before and after surgery.

Serologic Markers Used In Breast Cancer

Serial measurement of tumor markers after primary treatment for breast cancer can detect preclinical recurrent disease with lead times of about 2 to 9 months. But the clinical significance of this finding is unknown. In 1996, an American Society of Clinical Oncology expert panel recommended that a five- to tenfold increase of CA 15-3 above the normal limit be considered an alert for the presence of metastatic disease. However, the assay lacks sensitivity and specificity, and increased levels of this antigen can be seen in individuals with no breast cancer.

The following serologic markers are frequently used in current practice to monitor disease status of patients with breast cancer.

CA 15-3 Carcinoembryonic antigen HER2 extracellular domain

ASCO recently updated its guidelines for the use of tumor markers in breast cancer. The ASCO panel recognized CA 15-3, CA 27.29, and CEA to be of clinical utility in breast cancer management. A literature review of the utility of serum tumor markers in breast cancer has been published elsewhere.

Both CA 15-3 and CA 27.29 received US Food and Drug Administration approval in 1996 to be used in surveillance for disease recurrence or metastasis in patients with stage II/III breast cancer.

MUC1 Markers

Carcinoembryonic Antigen

HER2 Extracellular Domain

Circulating Tumor Cell Test

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Stage The Stage Is The Main Prognostic Factor For Breast Cancer There Is Less Risk That Early Stage Breast Cancer Will Come Back So It Has A More Favourable Prognosis Breast Cancer Diagnosed At A Later Stage Has A Greater Risk Of Recurrence So It Has A Less Favourable Prognosis Doctors Will Consider If Cancer Has Spread To Lymph Nodes And The Size Of The Tumour When They Predict A Prognosis

If cancer has spread to lymph nodes

Whether or not cancer has spread to lymph nodes is the most important prognostic factor for breast cancer. Breast cancer that has spread to lymph nodes has a higher risk of coming back and a less favourable prognosis than breast cancer that has not spread to the lymph nodes.

The number of lymph nodes that contain cancer is also important. The more positive lymph nodes there are, the higher the risk that breast cancer will come back. Breast cancer that has spread to 4 or more lymph nodes has the highest risk for recurrence.

The size of the tumour

The size of the tumour is the 2nd most important prognostic factor for breast cancer. The tumour size will affect prognosis no matter how many lymph nodes have cancer in them.

Breast tumours that are 5 cm or larger are more likely to come back after treatment than smaller tumours. Breast tumours that are smaller than 1 cm and have not spread to the lymph nodes have a very favourable prognosis.

What Do The Results Mean

ASCO 2010: Prognostic and predictive markers in breast cancer

Depending in what type of test you had and how it was used, your results may:

  • Help diagnose the type or stage of your cancer.
  • Show whether your cancer treatment is working.
  • Help plan future treatment.
  • Show if your cancer has returned after you’ve finished treatment.

If you have questions about your results, talk to your health care provider.

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Prospective Studies Of Tumor Markers

To further define the role of tumor markers in the monitoring of metastatic disease, several prospective studies were performed. Clinical utility of individual tumor markers was prospectively evaluated using CEA, CA 15-3 and TPS . One hundred twenty-nine women with metastatic breast cancer were followed for 6 months. The sensitivity for CA 15-3 was 73% vs. 69% for TPS. In another small, multi-center prospective trial, 83 women with metastatic breast cancer were assessable for following an established biochemical index, which included measurement of CA 15-3, CEA and ESR . Treatment response was measured by standardized criteria at baseline and at 3 month intervals. Eighty four percent of women had an elevation of at least one biochemical marker upon initial assessment. In this study, changes in tumor markers corresponded to standard criteria for disease progression at first assessment in 34/37 patients. In the 3 women whose markers were falling at 3 months, they were found to have progressive disease by standardized criteria. In women with late progression 13/17 had tumor marker elevation between 3-9 months prior to progression as measured by standard criteria. Three women that never had an elevated index remained in remission for the duration of this study.

Monitoring Treatment Response In The Adjuvant Setting

After completion of adjuvant therapy, follow up care focuses on detecting recurrent disease with the intention of improving long term survival. Surgical aspects focus on complete pathologic assessment of disease that will guide decisions on adjuvant therapy. Radiographic studies then provide non-invasive means to detect recurrent or new disease while regular follow up with a medical oncologist to discuss any new or concerning symptoms also aims to detect recurrent disease as early as possible in an attempt to improve survival by early treatment of recurrence or metastases.

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Are There Drawbacks To Tumor Marker Tests For Breast Cancer

While the results of a tumor marker test can be informative, theyre not conclusive. A low result doesnt mean you dont have cancer or are in remission.

For example, CA 15-3 is elevated in less than 50 percent of people with early breast cancer and in 80 percent of people with metastatic breast cancer. This means that theres a significant number of people who receive a normal tumor marker result while still having cancer.

Similarly, a high result doesnt always mean cancer is growing and spreading or that your treatment isnt working. Thats because its possible for various noncancerous conditions to cause elevated levels of some tumor markers.

As such, the American Society of Clinical Oncology doesnt currently recommend the use of tumor markers for screening, diagnosis, or detecting cancer recurrence.

They do note that some tumor marker tests, such as those for CA 15-3/CA 27.29 and CEA, may be used along with other tests to guide treatment decisions in metastatic breast cancer.

Testing for tumor markers can also be expensive. A 2015 study of 39,650 people with early-stage breast cancer found that medical costs for those who had at least one tumor marker test were about 29 percent higher.

Lastly, receiving a high result can be distressing. The additional follow-up testing to determine the cause of the elevated markers can also lead to anxiety.

Can A Tumor Marker Be Used To Screen For Cancer

Prognostic markers on Breast 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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Detection Rates At Baseline

CTC and serum marker values at inclusion repartition in percentile, mean, median range are given in Table and Figure . Values for serum markers are expressed in ULNV: upper limit of normal value. Table shows elevated serum marker and CTC incidence rates at baseline: CA 15-3 and CYFRA 21-1 were the two most commonly elevated serum markers. Serum markers and CTC were highly correlated to performance status, number of metastatic sites and to each other. Table shows the percentage of patients who had at least one marker elevated at baseline according to different marker combinations. As expected, this percentage globally increases with the number of markers assessed. However, the combination of CA 15-3 and CYFRA 21-1 retrieved almost the same positivity rate than all four markers .

Table 1 CTC and serum marker values repartition at inclusion

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.
  • Later-stage breast cancer is stages IIIB and IV . The cancer has spread beyond the breast and lymph nodes under the arm.
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    Expert Review And References

    • American Cancer Society. Breast Cancer. 2015: .
    • de Boer M, van Dijck JA, Bult P, Borm GF, Tjan-Heijnen VC. Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases. Journal of the National Cancer Institute. Oxford University Press 2010.
    • Lonning PE. Breast cancer prognostication and prediction: are we making progress?. Annals of Oncology. Oxford: Oxford University Press 2007.
    • Morrow M, Burstein HJ, and Harris JR. Malignant tumors of the breast. DeVita VT Jr, Lawrence TS, & Rosenberg SA. Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins 2015: 79: 1117-1156.
    • Tripathy D, Eskenazi LB, Goodson, WH, et al. Breast. Ko, A. H., Dollinger, M., & Rosenbaum, E. Everyone’s Guide to Cancer Therapy: How Cancer is Diagnosed, Treated and Managed Day to Day. 5th ed. Kansas City: Andrews McMeel Publishing 2008: pp. 473-514.

    Breast Cancer Tumor Markers Can Help Detect Cancer

    Tumor Marker Tests During Breast Cancer Follow Up

    Tumor markers are proteins and other substances found in blood, urine, or body tissues that can help detect cancer in someone with no other signs or symptoms. They can also sometimes indicate how aggressive a cancer is and whether it is responding to treatment. In breast cancer, however, tumor markers are less reliable indicators than in some other malignancies.

    Tumor markers generally are not as significant in breast cancer as they are in other cancers, said Erika Hamilton, MD, Director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute at Tennessee Oncology in Nashville.

    The American Society of Clinical Oncology guidelines do not recommend routine use of tumor markers to look for recurrence, she said. Similarly, they are not recommended by the National Comprehensive Cancer Network to follow metastatic disease routinely, but can be helpful in certain situations such as bone-only disease where radiographic modalities such as CT and bone scan may be less reliable.

    What Tumor Markers Are Used for Breast Cancer?

    There is no point a breast tumor marker is definitely recommended for breast cancer. Ovarian cancer, for example, has objective criteria that are based on the tumor marker CA-125, said Dr. Hamilton. Sometimes we use tumor markers in other clinically difficult settings, CA 15-3 being the most common.

    My Tumor Marker Numbers Are High. Does That Mean I Have Breast Cancer?

    Suzanne Mooney

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    Are There Any Risks To The Test

    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.

    There is no risk to a urine test.

    If you have had a biopsy, you may have a little bruising or bleeding at biopsy site. You may also have a little discomfort at the site for a day or two.

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