Study Population And Inclusion Criteria
A total of 331 female patients who underwent breast surgery at Zhongnan Hospital of Wuhan University between June 2012 and December 2015 were included into this study. A retrospective analysis of the clinicopathological data collected from 151 breast cancer patients was conducted. Inclusion criteria for these patients were: being pathologically confirmed as invasive breast cancer patients with no history of cancer and with complete clinicopathological data, including age, tumor size, clinical stage, axillary lymph node status, expression of ER, PR and Ki-67. Meanwhile, 180 age-matched control subjects were also selected. These control subjects were pathologically confirmed as breast benign diseases, including mammary hyperplasia and fibroadenoma. This study was approved by the ethics committee of Zhongnan Hospital of Wuhan University, in accordance with the Declaration of Helsinki. Written informed consents were obtained from all patients.
Tumor Markers In Breast Cancer Systematic Review
Cancer today. http://gco.iarc.fr/today/home.
Redig A, McAllister S. Breast cancer as a systemic disease: a view of metastasis. J. Intern. Med. 2013 274:113-26. doi: 10.1111/joim.12084.
Sundquist M, et al. Improved survival in metastatic breast cancer 1985-2016, Breast. 2016 31:46-50. doi: 10.1016/j. breast.2016.10.005.
Taplin S, et al. Mammography facility characteristics associated with interpretive accuracy of screening mammography. J Natl Cancer Inst. 2008 100 : 876-87. doi. 10.1093/jnci/djn172.
Mandelblatt JS, et al. Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms. Ann Intern Med. 2009 151 : 738-47. doi. 10.7326/0003-4819-151-10-200911170- 00010.
Duffy M. Serum tumor markers in breast cancer: are they of clinical value? Clin. Chem. 2006 52: 345-51. doi. 10.1373/ clinchem.2005.059832.
Molina R, et al. Tumor markers in breast cancer -European Group on Tumor Markers recommendations. Tumour Biol. 2005 26: 281-93. doi. 10.1159/000089260.
Cheung K, et al. Tumour marker measurements in the diagnosis and monitoring of breast cancer. Cancer Treat. Rev. 2000 26: 91-102. doi. 10.1053/ctrv.1999.0151.
Harris L, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J. Clin. Oncol. 2007 25: 5287-312. doi. 10.1200/JCO.2010.33.7311.
How To Get Brca Genetic Testing
Genetic counseling is recommended for those who are interested in being tested for breast cancer gene mutations. You can talk to a doctor about getting a referral to a genetic counselor, who can help determine whether genetic testing would make sense based on family history and risk factors. Since many genetic tests only look for one specific gene mutation, the counselor can often help determine which mutations to test for.
The genetic test itself simply involves taking a small sample of blood or saliva, which is sent to a lab for analysis. Results can take several weeks or months.
Genetic testing results are not always clear-cut:
- A test result can be positive, meaning that the patient does carry the gene mutation.
- A negative test result indicates that they do not have that particular known gene mutation. It does not, however, rule out the possibility of having mutations in other genes. It also does not rule out the possibility of developing breast cancer. Most breast cancer cases are not hereditary, so everyone should still have an early detection plan.
- Genetic test results can also be uncertain or ambiguous. An ambiguous test result means that a mutation has been found on the gene, but it is not yet known whether that particular mutation has any effect on the chances of developing breast cancer.
- Someone is either negative or positive. Over time, a person cannot go from being negative to being positive or vice versa for the specific gene mutations they were tested for.
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Implications For Genetic Testing
The results presented above on the morphological and immunohistochemical characteristics of hereditary breast cancer illustrate major differences between genotypes. The most important were those between tumors in BRCA1 carriers and all other categories. These histopathological features, in conjunction with clinical data, can be used to predict BRCA1 status and, to a lesser extent, BRCA2 and non-BRCA1/2 status and this could have implications for the process of mutation screening.
In families with a high incidence of breast and ovarian cancer there is a high probability of finding a BRCA1 or BRCA2 germline mutation. In the absence of other clinical features suggesting the alteration of a specific gene, such as prostate cancer and BRCA2 mutations, histopathological features can be used to indicate which gene should be screened first. Grade 3, estrogen receptor- and progesterone receptor-negative infiltrating ductal carcinomas are more common among BRCA1 patients, specially if they show medullary features. These cases should be also tested for CK5/6 and EGFR expression, since the positive staining of any of these makers further increase the probability of being a BRCA1 mutation carrier. Estrogen receptor- and/or progesterone receptor-positive tumors without evidence of basal differentiation should first be tested for BRCA2 mutations.
Whats An Example Of How Tumor Marker Testing Can Guide Cancer Care
Understanding how tumor markers can affect your treatment choices can be complicated, but asking for examples can help. For instance, early-stage breast cancer has specific tumor markers that can help doctors tailor an individuals treatment. If a person is diagnosed with this disease, the doctor may test for tumor markers known as estrogen receptor and progesterone receptor . If the tests are positive for them, her doctor knows that the patient is more likely to be treated successfully with hormone therapy.
If your doctor suggests tumor marker testing, ask which tumor markers youll be tested for and how often. Also, ask what the doctor hopes to learn from the testing.
What Do Your Results Mean
Your circulating tumor marker blood test results will include a numerical value that will either be in a normal range or considered high. Below are the ranges for the tumor markers above, according to the National Institute of Cancer.
CA 15-3: Normal, less than 30U/mL. High, 30 U/mL or higher.
CA 27-29: Normal, less than 38 U/mL. High, 38 U/mL or higher.
CEA: Normal, less than 2.5 ng/mL. Extensive disease, greater than 10 ng/mL. Metastatic disease, greater than 20 ng/mL.
CA 125: Normal, less than 35 U/mL. High, greater than 35 U/mL.
CTCs: Normal, n/a. High, greater than 5 CTCs per 7.5 mL of blood.
As mentioned, when the markers are in that high threshold, that could indicate more active disease. However, its not a perfect science. You may experience fluctuations even when your cancer hasnt spread. What we really look at are the trends over timeif the tumor marker is consistently going up month after month, says Dr. Cohen. When that happens, it means your cancer is possibly resistant to the treatment and your doctor will likely order more tests, including another set of scans to confirm. We seldom make decisions based on the tumor markers alone, he says.
Why Are Tumor Marker Tests Used For Breast Cancer
There are two main types of tumor markers: circulating tumor markers and tumor tissue markers .
Circulating tumor markers are proteins or other substances pumped out by cancer cells that wind up in your bloodstream, stool, and urine when you have certain cancers. The levels in your blood can give your doctor an idea about how active your cancer is, your prognosis, if your cancer has returned, and how its responding to treatment. Elevated tumor markers are typically associated with a higher burden of disease, says Dr. Cohen. Your doctor may check them regularly during your course of treatment to see how the markers are changing over time, as well as after treatment to monitor for recurrence.
Then there are tumor tissue or cell markerssometimes referred to as biomarkerswhich are found in the tissue of the tumor itself. Theyre used more when determining the type of breast cancer you have: human epidermal growth factor receptor 2 , estrogen or progesterone receptor positive . These tumor markers tell us about the specific biology of the cancer, says Amber Guth, M.D., professor of surgery and director of breast cancer interdisciplinary fellowship at NYU Langone Health in New York City. They can also help determine your prognosis as we know some cancers are more aggressive than others, and they can help doctors put together individualized treatment. For example, for HER2+ breast cancer, there are targeted treatments that address this specific genetic mutation.
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How Do I Interpret The Genetic Test Results
A negative genetic test means that a breast cancer gene mutation was not identified. If other genetic testing has identified a mutation in your family, a negative test means you do not have the specific mutation. Therefore, your risk of cancer is the same as someone in the general population who has a family history of breast cancer.
If a BRCA1 or BRCA2 mutation has not been previously found in your family, a negative result should be interpreted cautiously. There is still a chance that you may be at higher risk for breast cancer because of changes in genes other than those that doctors can test for.
A positive test result means that a mutation known to raise the risk of breast and ovarian cancer was identified.
If I Have A Brca Gene Mutation Will I Get Cancer
A BRCA mutation increases the risk of getting certain types of cancers, Clayback says. However, not all people with BRCA mutations will get cancer.
For example, approximately 12% of women in the general population will develop breast cancer at sometime in their lives. But, for women with a BRCA1 or BRCA2 mutation, the risk of developing breast cancer increases to as much as 72%. Likewise, about 1 to 2% of women in the general population will develop ovarian cancer sometime during their lives, but up to 44% of women who inherit a harmful BRCA1 mutation and about 17% of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by the age of 80.
How Do You Test For Cancer Markers
- Flow cytometry. This test is used to diagnose and classify certain cancers, such as leukemia and lymphoma, and to evaluate the risk of recurrence.
- Mammaprint + Blueprint ® test. The Mammaprint ® 70-Gene Breast Cancer Recurrence Assay may be used to determine the risk that a patients cancer will return.
- Oncotype DX ® test.
- MammaPrint + BluePrint ® vs.
Literature Mining Confirms The Genes Screened
Next, we take the intersection of the obtained differentially expressed genes and the Hub genes obtained in the previous step to obtain a narrow and reliable biomarker list for breast cancer diagnosis.
To test whether the biomarkers screened in our study are indeed associated with breast cancer, we use PubMed to conduct a literature review, and analyze whether the genes are indeed related to breast cancer in previous reports, so as to prove that the screening of tumor-related genes using our methods is effective. PubMed is a widely used search engine, built and maintained by the National Biotechnology Information Center of the National Library of Medicine , which can provide more than 28 million academic biomedical publications.
This method is simple and feasible. The selected genes and breast cancer will be searched as the keywords in the literature database, and then consult the literature to see if there is a strong or weak relationship between the screened genes and the occurrence and development of breast cancer.
What Is A Tumor Marker
A tumor marker is anything present in or produced by cancer cells or other cells of the body in response to cancer or certain benign conditions that provides information about a cancer , such as how aggressive it is, what kind of treatment it may respond to, or whether it is responding to treatment.
Breast Cancer Tumor Markers Can Help Detect Cancer
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 , 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 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.
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Pathways And Biological Functions Differentially Expressed Genes Involved
DAVID bioinformatics tool was employed to complete the Gene Ontology and KEGG pathway enrichment analysis. From the result of enrichment, we can see that the differentially expressed genes are involved in a number of cancer-related biological functions, such as cellular protein metabolic process, negative regulation of gene expression, epigenetic, response to drug, cell development, transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding et al. . Through the bubble diagram, it can be seen intuitively that the GO function and KEGG pathway enriched by the 1060 differentially expressed genes. It is significant that these genes annotate the transcriptional misregulation in cancer pathway, suggesting that these genes may be closely related to cancer development and may serve as potential biomarkers for breast cancer.
Gene enrichment analysis. Gene enrichment analysis of Gene Ontology. Gene enrichment analysis of KEGG.
In addition, a total of 28 significantly enriched pathways were identified , including Neuroactive ligand-receptor interaction, Systemic lupus erythematosus, Chemical carcinogenesis, Metabolism of xenobiotics by cytochrome, Drug metabolismcytochrome P450, Transcriptional misregulation in cancer, cAMP signaling pathway et al. This suggests that the occurrence and development of breast cancer is a complex physiological process, with abnormal functions in a variety of pathways.
What Are The Tumor Markers For Breast Cancer
Not all cancers have known tumor markers, but breast cancer does have a few specific markers that doctors will check for. These include:
Cancer-antigen 15-3: This tumor marker is specific to breast cancer.
CA 27.29: This marker is interchangeable with CA 15-3, so doctors will generally check one or the other.
Carcinoembryonic antigen : This tumor marker is elevated in breast cancer patients, as well as colon, stomach, and lung cancer patients.
CA-125: This one is associated with ovarian cancer and ascites, which is when fluid made up of malignant cells collects in the stomach. In some cases, CA-125 is elevated with metastatic breast cancer.
Circulating tumor cells : These are cells that break off from the cancer and find their way into your bloodstream. If your CTCs level is elevated, its an indication that your cancer may be growing.
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Why Are Tumor Marker Tests Used
Along with other tests, tumor marker tests can help doctors diagnose cancer and recommend a treatment plan for an individual. Why, when, and how often these tests are done varies greatly from person to person. Rarely, they are used to help screen for a particular type of cancer in people with a high risk of the disease before they have signs and symptoms. But doctors mainly use tumor marker tests to:
Figure out how well a treatment is working
Predict a persons chance of recovery
Predict how likely it is a cancer will come back after treatment and find it if it does
What Are Tumor Marker Tests For Breast Cancer
Tumor markers are typically proteins that are produced by cancer cells, many of which can be found in the blood. Some examples of such tumor markers in breast cancer are:
- CA 15-3 and CA 27.29: CA 15-3 and CA 27.29 are two related markers that are made in higher amounts by breast cancer cells. As such, when theyre found in the blood, they can signal the presence of breast cancer.
- Carcinoembryonic antigen :CEA is a marker thats often used for colorectal cancer. However, it can also be applied to other types of cancer as well, including breast cancer.
- CA 125: CA 125 is a marker thats most often associated with ovarian cancer, but can also be a sign of breast cancer.
Additionally, sometimes parts of a tumor can break off and circulate in the blood. These circulating tumor cells can also be used as a tumor marker. High amounts of CTCs in the blood can mean that cancer is growing and spreading.
Tumor marker tests can be used by doctors to gauge the level of cancer activity in your body. This information may be useful to:
- evaluate how your cancer is responding to your current treatment
- see if your cancer has spread to other areas
- determine if a cancer thats been in remission has come back
Tumor marker tests can help to inform treatment decisions. For example, if a tumor marker is elevated, it may indicate that your current treatment isnt working. Your doctor may use this information to switch or adjust your treatment.
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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.