What is a Tumor Marker?
Original post July 17, 2008
The following is extracted from the American Cancer Society’s web site: http://www.cancer.org/docroot/PED/content/PED_2_3X_Tumor_Markers.asp?sitearea=PED:
Tumor markers are substances that can be found in the body when cancer is present. They are usually found in the blood or urine. They can be products of the cancer cells themselves or of the body in response to cancer or other conditions. Most tumor markers are proteins.
There are many different tumor markers. Some are seen only in a single type of cancer, while others can be found in many types of cancer.
To test for a tumor marker, the doctor sends a sample of the patient's blood or urine to a lab. The marker is usually found by combining the blood or urine with manmade antibodies designed to react with that specific protein.
For many reasons, tumor markers by themselves are usually not enough to diagnose or rule out cancer. Most tumor markers can be made by normal cells as well as by cancer cells. Sometimes, non-cancerous diseases can also cause levels of certain tumor markers to be higher than normal. And not every person with cancer may have higher levels of a tumor marker.
For these reasons, only a handful of tumor markers are commonly used by most doctors. When a doctor looks at the level of a certain tumor marker, he or she will consider it along with the results of the patient's history & physical exam and other lab tests or imaging tests.
How Are Tumor Markers Used?
Screening & Early Detection of Cancer: Screening refers to looking for cancer in people who have no symptoms of the disease. Early detection is finding cancer at an early stage, when it is less likely to have spread & is more likely to respond well to treatment. Although tumor markers were first developed to test for cancer in people without symptoms, very few markers have been shown to be helpful in this way.
The most widely accepted tumor marker is the prostate-specific antigen (PSA) blood test, which is used (along with the digital rectal exam) to screen for prostate cancer. But because it's not always clear what the test results mean, not all doctors agree that PSA screening is appropriate for all men. Newer versions of the PSA test may prove to be more accurate.
Most other tumor markers have not been shown to detect cancer much earlier than they would have been found otherwise...
Determining the Effectiveness of Cancer Treatment: One of the most important uses for tumor markers is to monitor patients being treated for cancer, especially advanced cancer. If a tumor marker is available for a specific type of cancer, it is much easier to measure it to see if the treatment is working rather than repeating chest x-rays, CT scans, bone scans, or other tests. It also tends to be less expensive.
If the tumor marker level in the blood goes down, it is almost always a sign that the treatment is having an effect. On the other hand, if the marker level goes up, then the treatment probably should be changed. (One exception is if the cancer is very sensitive to a certain chemotherapy treatment. In this case, the chemotherapy can cause many cancer cells to die & release large amounts of the marker into the blood, which will cause the level of the tumor marker to rise for a short time.)
Detecting Recurrent Cancer: Markers are also used to look for cancer that may come back (recur) after initial treatment. Some tumor markers may be useful once treatment is complete and there is no evidence of cancer remaining…
Some women who have been treated for breast cancer have yearly blood tests for levels of the tumor marker CA 15-3. This can sometimes detect cancer recurrence before the woman has symptoms or evidence of cancer on imaging tests. Many doctors question the test's value, though, because no one has shown a long-term advantage in finding recurrent breast cancer early. And usually the cancer causes symptoms or can be found by the doctor around the same time that the CA 15-3 level rises…
Because of this, some doctors & medical groups do not recommend using these tumor markers after treatment aimed at curing these cancers. They are more likely to be used to monitor more advanced cancer, especially when treatment may not be expected to result in a cure, as mentioned above…
Specific [Breast Cancer] Tumor Markers:
CA 15-3: It is used mainly to monitor patients with breast cancer. Elevated blood levels are found in less than 10% of patients with early disease and in about 70% of patients with advanced disease. Levels usually drop following effective treatment, although they may spike in the first few weeks after treatment is started, a result of dying cancer cells spilling their contents into the bloodstream.
The normal level is usually less than 25 U/mL (units/milliliter), depending on the lab. But levels as high as 100 U/mL can sometimes be seen in women who do not have cancer. Levels of this marker can also be higher in other cancers and in some non-cancerous conditions such as benign breast conditions and hepatitis.
CA 27.29: CA 27.29 is another marker used to follow patients with breast cancer during or after treatment. This test measures the same marker as the CA 15-3 test, but in a different way. Although it is a newer test than CA 15-3, it does not appear to be any better in detecting either early or advanced disease. It may be less likely to be positive in people without cancer. The normal level is usually less than 38 to 40 U/mL (units/milliliter), depending on the testing lab. This marker can also be elevated in other cancers and in some non-cancerous conditions, and it may not be elevated in some women with breast cancer… (This is the tumor marker I have measured & report)
Estrogen receptors/progesterone receptors: Breast tumor samples--not blood samples--from women and men with breast cancer are commonly tested for these markers. Breast cancers that contain estrogen receptors are often referred to as "ER-positive," while those with progesterone receptors are "PR-positive." About 7 out of 10 breast cancers test positive for at least one of these markers. These cancers tend to have a better prognosis than cancers without these receptors and are much more likely to respond to hormonal therapy such as tamoxifen or aromatase inhibitors… (As I mentioned in chapter 5 of my story, my cancer is “ER positive;” it is also “PR positive.” In my chapter 11 blog, I discuss the fact that we chose hormone therapy with an aromatase inhibitor.)
. . . No tumor marker has been found to be useful for screening or for the diagnosis of early stage breast cancer.
At the time of diagnosis, breast cancer tissue is often tested for estrogen and progesterone receptors, as well as the HER2/neu antigen. These markers provide some information on how aggressive the cancer may be & how likely it is to respond to certain treatments.
The markers most commonly used to follow patients with advanced cancer or to detect recurrence are CA 15-3 & CEA. The CA 27.29 test is also used by some doctors. The CA 15-3 & CA 27.29 are probably equally sensitive, while the CEA is less sensitive.
These markers are most useful in measuring the results of treatment for patients with advanced disease. Generally speaking, blood levels go down if the cancer responds to treatment & rise if the cancer progresses.
Some doctors use these tests to look for signs of recurrence in women who have no symptoms of cancer after their first treatment. But most professional groups do not recommend using these markers to follow women already treated for early stage disease…
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I hope this helps you to have a better understanding of tumor markers.
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What is a PET Scan?
Original post May 20, 2009
I am describing the PET scan first to help you understand what it is &, second, to inform you of its significance.
What is it?
PET (or positron emission tomography) is a medical imaging tool. It is used to detect and to monitor cancer. The device used looks like a CT scanner, and, in fact, the scans I have simultaneously perform both a CT & a PET scan.
A PET scan is very different from an ultrasound, X-ray, MRI, or CT. Unlike these imaging technologies which merely confirm the presence of a mass; they cannot determine whether a tumor is still active once it is determined that it is malignant. A PET scan can distinguish between benign and malignant disorders.
PET can help physicians effectively pinpoint the source of cancer. It can detect abnormalities in cellular activity, generally before there is any physical change. It can visualize a tumor in size from 7mm to 1cm depending on the location. This is smaller than the other technologies, which typically detect tumors that are 1cm or larger.
Cancer cells have a much higher metabolic rate than other cells. One characteristic is that cancer cells need higher levels of glucose for energy. This is the biological process PET measures.
As part of the procedure, a form of slightly radioactive glucose (sugar) is injected into the patient about 45 minutes prior to the scan. The cells of the body absorb this sugar, which releases atomic particles called positrons. These positrons combine with electrons in the body to produce gamma rays. As gamma rays leave the body, they are detected by a special camera. The recorded emissions provide a three-dimensional map of how glucose is used throughout the body. The images from the scanner contain varying colors or levels of brightness that help physicians identify abnormalities, such as the presence of cancer. For example, cancerous tissues use more energy and absorb more sugar than healthy tissues. For this reason, these malignant areas appear brighter than normal tissues on PET scan images.
You may wonder why radioactive glucose is used. Cancer cells demonstrate a 3 to 5 fold increase in glucose uptake compared to healthy cells. That is what it means when the sentence above says, “they have a much higher metabolic rate than other cells.” Another way to say it is to say, cancer is a sugar-feeder. Scientists call it an “obligate glucose metabolizer.” Cancer cells primarily use glucose for fuel.
You can slow cancer growth by lowering the amount of fuel available to the tumor cells. This is the reason my diet eliminates all sugar. It also eliminates or restricts foods with a high glycemic index. I eat fruits but not bananas because they are too quickly converted to glucose. I do not eat refined grains for the same reason. When I have whole or multi-grains I must have them with a source of protein to keep my blood sugar level from rising significantly. I do not eat vegetables that grow below the ground, except garlic & onions, for the same reason. Raw carrots are permissible, as they are not quickly converted to glucose.
As you can imagine, it makes my decisions easier when I know that to eat the right foods I am feeding my body, but to eat the wrong foods I am feeding the cancer. I certainly don’t want to feed the cancer cells!!
What is its significance?
My first PET scan was done December 18, 2007. At that time, I had a malignant lymph node that was just over 2 cm, in my left armpit, removed. I had a 2 cm biopsy of 2 calcifications in my left breast, which did not appear suspicious on the digital mammogram or ultrasound, that was malignant, & the surgeon did not get clean margins. A CT scan in September indicated that there were some nodules on each lung, but I was advised to have them rechecked in 6 months. Dr. Patel, my oncologist, decided to order a PET scan to make a final diagnosis with respect to the stage of my cancer. From the above description, you can see that a PET scan is the only technology that can pinpoint all sites where cancer is present. This PET scan revealed that my cancer has metastasized (spread) from my left breast to 4 lymph nodes under my left arm, multiple lymph nodes along the mediastinum (behind the breast bone), & several small nodules on both lungs. The fact that the cancer has spread to a major organ causes it to be classified as stage IV.
By May 2008, I had 3 PET scans & my tumor marker had dropped in response to the medication I started taking December 27, 2007. Here is the progression of my numbers:
12/10/07 --- 211
PET scan 12/18/07 (staged cancer -- stage IV, metastatic breast cancer)
12/27/07 --- 291.3
Started aromatese inhibitor (AI) 12/27/07 It takes 1 month to take full effect. Dr. Patel expected the tumor marker to eventually drop into the 200 - 300 range.
1/30/08 --- 580.8 same day, apt. with Dr. Powers & changed my diet drastically
PET scan 2/19/08 (scan showed slight improvement, although we were told to expect no improvement or possibly worsening of the PET scan because it was too soon for the AI to have made enough of a difference)
2/27/08 --- 389.7
PET scan 5/6/08 (additional improvement)
5/14/08 --- 126.7
Dr. Patel explained that the tumor marker number showed a definite correlation with the PET scan results – the tumor marker increased until the medication was started & took full effect, then it dropped & the PET scan results showed improvement -- so that it was not necessary to undergo the additional radiation of the PET scan every 6 or 8 weeks, if the tumor marker results are valid. The tumor marker is determined from a blood sample.
Clinical normal for the CA 27.29 tumor marker is 38.8 or below. Since my blood work indicates that it has been in this range since December 2008, Dr. Patel decided he really does not know what the cancer is doing. The only way to know is to do another PET scan. This PET scan will show us what is going on & also reveal whether or not the tumor marker is, as we have assumed for this past year, reporting a valid picture of the state of my cancer.
My PET scan 5/12/09 shows the tumor marker numbers are, indeed, valid! At this time, it shows activity in only ONE lymph node under my left arm, and that activity is described as “barely visible & is probably not likely clinically significant at this time.” That’s as close as I can imagine to remission!! Praise God! Thank you for your prayers! There is NO activity in any of the other lymph nodes or nodules! Praise God!!!!
My ulcerative colitis (UC) previously showed up as a false positive. Guess what? It didn’t show up on this scan! In fact, I have been able to eliminate one of the medications I take for my UC. I was taking 2 pills a day of one medication & 12 a day of another. I have completely eliminated the medication that I was taking 12 pills a day. It’s incredible! I am healthier today than I was the day I was diagnosed with stage IV metastatic breast cancer! God is AWESOME!
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CTC -- New Diagnostic Test
Original post October 31, 2009
September 1, 2009. I meet with Dr. Gallagher, who treats my ulcerative colitis (UC). I report to him that I was able to taper off of the Asocol since I saw him in January, with no problems. He is pleased with this. My summarization of his explanation for my marked improvement: some patients have periods of time when their UC just spontaneously improves. I know why my UC has improved, & I’m extremely thankful for what I have learned about UC & the role that diet & nutritional supplements play in both controlling & improving this condition! I remind myself again of his lack of coursework in this area.
I ask Dr. Gallagher if he thinks I can decrease the other medication I take, from 2 pills a day to one each day.
He does a math calculation, using my weight & the number of milligrams I take per day, & says, “Yes, you can try it if you want to. If it is going to cause a flare-up, it will take 1-3 months.”
I am hopeful that this will not cause a flare-up. I trust it is God who has prompted me to make this request rather than just my eager desire to eliminate more prescription medicine that has caused me to charge ahead. Time will tell.
September 9, 2009. I have blood drawn for my tumor marker test. I assume it is much too early to know if the cottage cheese & flaxseed oil has made any difference yet. My life has been too crazy, in the past month, so that I have not had time to do the research to find out how long I can expect to wait until I see noticeable results in my diagnostic tests. I am just hopeful that the number will be lower than the 30.9 on July 8. That will make me happy.
Side note: Research done later states that it takes 3-6 months for diagnostic tests to show a noticeable difference. September 16, 2009. We meet with Dr. Patel for a routine check-up & to get my tumor marker results.
I jotted down a few questions before the appointment, so I wouldn’t forget to ask what I’d been thinking about between appointments.
Of course, my first question is, “What is my tumor marker number?” It is 29.2! It finally dropped below 30! This is a 5.5% decrease! As far as Dr. Patel is concerned, it is still in the normal range. This is a good thing! Period.
I ask if he has decided on November or December for the PET scan. He says it has already been set; the receptionist will give me the date when I leave today. (It happens to be October 30.)
He asks me the usual list of questions & does the usual exam. Then he asks what other questions I have. Yes, he knows me well enough to know I have more questions than the 2 above.
I say, “You once explained the tumor marker blood test as a microscopic test for the cancer as opposed to the gross look at the disease of the PET/CT scan. Can you give me more insight on this?”
Dr. Patel likes my question. He says it actually is an excellent lead-in to what he wants to discuss with us today.
I will try to keep this simple, but I am adding some background details & side notes as I relate portions of the discussion. I certainly don’t expect you to recall what I can recall from the past 2 years, about my journey with cancer, or to know what I have researched on the Internet.
Dr. Patel says, “First, why do we do all of these diagnostic tests? We want to know, when will the tumor become resistant to Femara?” .
Background info: I started taking Femara December 28, 2007. A short time after that, I learned that 12-14 months is the average span of time it takes before a patient’s cancer becomes resistant to the medication. I have been taking it for 21 & a half months, as of 9/16/09! I’m way past the average; I’m praising God!! When the cancer becomes resistant to the medication, in medical terms, it progresses. Likewise, in medical terms, I have been “progression-free” for 21 & a half months! A rising tumor marker number or a PET/CT scan that detects an area or areas of increased activity indicates disease progression &, in my case, these would be the indicators of resistance to the medication.
Dr. Patel’s point is: the constant testing is done to watch for the earliest sign of recurrence of my cancer, due to resistance to the Femara. I understand this point.
Side note: Although I know Dr. Patel is pleased that my tumor marker number has remained in the normal range since December of ’08, I get the sense that he is always hopeful that it will remain in that range, but expecting it, due to his experience with his other patients, to begin to increase at the next blood draw. I know that, initially, Dr. Patel told us to expect Femara to bring my tumor marker down from 580.8 to the 300 range & stabilize. In 2 months it dropped to 389.7. By 5 & a half months it dropped to 126.7! It declined into the normal range over the course of 12 months & continues to decline by small amounts.
I have had conversations with Dr. Powers on this topic, too. He has stated that Femara is not capable of bringing my tumor marker down this far, in this short period of time; so, he does not expect the tumor marker number to go back up. He believes it is the combination of things I am doing that is killing the cancer. Femara is only one part of my arsenal in this battle!! In fact, Dr. Powers thinks I could stop taking Femara, at this point, & the tumor marker number would not rise. I told him that I’m not ready to go that far! He says that it won’t hurt me to continue to take the drug. I feel at peace with the decision to continue taking it as part of my overall treatment plan. If it is making a difference, I don’t want to eliminate it. I am absolutely certain it has played a part in the results I have experienced to this point. Dr. Patel then reveals the exciting news he wants to tell us today about a new test called a CTC – circulating tumor cells test. I listen to his explanation once & take some notes, & then pause to read the notes before asking him to explain it again, as I ask some specific questions, to understand the CTC & to get my original question answered.
I will summarize this & try not to lose you in a bunch of medical mumbo jumbo.
Dr. Patel explains by comparing the diagnostic tests he uses to monitor my response to my current treatment with a new test he is adding – CTC – Circulating Tumor Cells test.
CA 27.29 tumor marker blood test – He explains that this test is not very sensitive or specific. It is actually a protein in the blood that is produced by the cancer cells; however, these proteins can be produced by other conditions. Some breast cancer patients do not experience an elevation in this tumor marker. Thus, a woman with breast cancer may or may not have an elevated CA 27.29 tumor marker.
Side note: If you read “What is a Tumor Marker,” above, it describes the process through which it was determined that my tumor marker number is reliable.
PET scans are more sensitive. What does this mean? They can detect tumors .7 cm & larger. [This is just a little larger than a ¼ of an inch, which is] large enough to be seen by the human eye. Dr. Patel’s terminology is: “it can see gross disease in the body.” PET helps physicians effectively pinpoint the source of cancer. It can detect abnormalities in cellular activity, generally before there is any noticeable physical change. The abnormalities in cellular activity are detected on a gross level rather than a microscopic level.
Side notes: “What is a PET scan,” above describes a PET/CT scan & its significance. Unlike ultrasound, X-ray, MRI, or CT, which merely confirm the presence of a mass, a PET scan can distinguish between benign and malignant disorders. Greater activity in a malignant tumor shows on the scan as brighter spots of color than low levels of activity in a malignant tumor. It is not capable of seeing individual cells.
In contrast, CTC is highly sensitive & highly specific in looking for cancer cells themselves floating in the blood. It is more reliable than the CA 27.29 tumor marker because it is counting actual cancer cells in the blood rather than measuring a protein that may or may not be produced by cancer cells. Results are numerical, which will rise in response to the progression of cancer before it is detectable or visually evident by other blood tests or by imaging technology. This means it can detect disease progression much sooner than any of the imaging technologies. (If it has been determined that a patient’s tumor marker is reliable, will the CTC still detect recurrence sooner than the CA 27.29? This is good question for my next appointment. It’s VERY difficult to think of every question I might want to have answered in the middle of a discussion of something so foreign to my everyday realm of knowledge.) If the number is less than 5 cancer is not progressing. If it is greater than 5, it is progressing. Because the blood test is done each month, it is easy to see how fast change is occurring. The most important purpose of this test is for detection of recurrence, & the rate of change is used to make prognosis, as well as treatment decisions.
It is my understanding, from our discussion, that the cut-off number of 5 is to allow for a margin of error in the test. I will go home & research CTC on the Internet & hope to gain a better understanding.
I ask if I will still have the CA 27.29 tumor marker blood test done, if we are going to do the CTC test.
Dr. Patel says that he sees no reason to stop it. It cannot hurt to have more data.
We feel comfortable with this choice, especially when we are familiar with watching this number, know its significance & know that mine has been proven to be reliable.
I have blood drawn to have my first CTC test today. Dr. Patel expects the number to be 0. I think this would be wonderful! That’s my expectation.
September 23, 2009. I call Dr. Patel’s office to see if my CTC test number is available. The receptionist puts the P.A. on the phone, & she excitedly tells me that the number is 3, which she says is really good! Well, it is, but I was expecting 0. I flatly tell her, “Yes, it is” & thank her. I was disappointed.
Ed tells me that I’d be upset if Dr. Patel wouldn’t commit to a prediction, & when he gives me one that’s wrong & disappointing, I’m upset. The poor man can’t win! I know; I just had my hopes too high.
I am happy with the decision to continue the tumor marker blood test, since I am used to watching this number & because Dr. Powers made the statement about 10 to 15 as the range where he will consider me to be cancer-free. I want to see how this corresponds with the CTC test number. Will it decrease to 0 over that same period of time? Only time will tell.
Side notes: I researched the CTC test online to learn more about it. I think I understand it a little better now.
The CTC is a relatively new test. It was approved for use in 2007, but only for breast, colorectal, & prostate cancer. http://www.easttnmedicalnews.com/news.php?viewStory=1183
Used in combination with imaging & all the other important parts of your therapy, the CTC test can help your doctor make more informed decisions regarding your care… CTCs are cancer cells that have detached from a solid tumor and entered into the bloodstream. These cells play an important role in the metastatic process, and their presence can provide valuable insight into disease progression. http://www.carolinabiooncology.org/cell_search.html
Interpretation of my CTC of 3: In the sample of blood drawn there was an average of 3 cancer cells found per 750 ml (about 1.5 tsp.) of blood. Because these circulating tumor cells are not taking up residence & beginning new tumors in other parts of my body, my cancer is not progressing. Instead, my immune system is strong enough that it is killing them & escorting them out of my body! Praise God! I also realize the fact I have circulating tumor cells is confirmation that, although my PET/CT scan shows there is only slight activity in one lymph node, I do still have living cancer cells in the tumors that do not show any detectable cancer, on the May 12th PET/CT scan. It also indicates the need for me to keep my immune system strong so that it will continue to function as God designed it to function.
In the blog about “The Growth Rate of Cancer Cells” I describe how a healthy immune system recognizes & destroys mutant cells, & I describe some of the major factors that cause our natural defense system to fail. Knowing that I have even a small number of live cancer cells circulating in my blood stream makes me mindful of the need to remain vigilant in the war against this disease & with my strategies to keep my immune system strong. (Philippians 4:13 “I can do everything through him who gives me strength.” Psalm 28:7 “The Lord is my strength & my shield; my heart trusts in him, & I am helped. My heart leaps for joy & I will give thanks to him in song.”)
After researching the CTC test online, I have several questions I want to ask Dr. Patel at my next appointment.
