What Is the Cancer Antigen 15-3 Blood Test?

A tumor marker test used to monitor metastatic breast cancer

female scientist, role of lab test CA 15-3 in breast cancer
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The cancer antigen 15-3 (CA 15-3) biomarker test is used to monitor breast cancer. The CA 15-3 antigen is a protein released into the bloodstream by certain types of cancer. Although breast cancer is closely linked to the CA 15-3 antigen, it is associated with other cancerous and non-cancerous conditions as well.

CA 15-3 is one of several substances classified as tumor markers, which increase as a malignancy progresses and decrease as a tumor responds to cancer therapy. The CA 15-3 is one of several tumor markers used to monitor people with stage 4 breast cancer (also known as metastatic breast cancer). While some oncologists will use the test to detect breast cancer recurrence, it is not endorsed for this use.

Purpose

CA 15-3 is an antigen found normally in breast tissue. Antigens are Y-shaped proteins that identify a cell to the body, acting as its unique "signature."

While the CA 15-3 antigen does not cause cancer, it can increase in number as cancer cells rapidly divide. Because cancer cells are "immortal" and do not undergo apoptosis (programmed cell death), the number of CA 15-3 antigens will increase in tandem with a tumor's growth.

With that said, not all breast cancers shed CA 15-3 antigens. This is especially true with early-stage breast cancer in which only 20% to 30% of women will show elevations in CA 15-3 values. By contrast, 50% to 60% of women with metastatic breast cancer will have increased CA 15-3 levels.

These dynamics make the CA 15-3 useful for monitoring stage 4 breast cancer in which a primary breast tumor has spread (metastasized), establishing secondary tumors in other parts of the body. If your oncologist orders a CA 15-3 test, it may be for one of two reasons:

  • By regularly tracking your CA 15-3 values, the oncologist can assess how effectively a cancer treatment is working.
  • If CA 15-3 antigens rise over a certain level, it may indicate a worsening of the disease and warrant the investigation of metastasis in other parts of the body (most often the bone or liver).

Limitations

Although the CA 15-3 test is valuable for monitoring breast cancer, it is less reliable when used for cancer screening. This is partly due to the fact that the CA 15-3 is specific to breast cancer but not exclusive to it. Other benign and malignant conditions can also cause increases, such as:

Even pregnancy and breastfeeding can increase CA 15-3 levels, giving the false impression of disease progression or recurrence.

Even beyond its non-specificity, the CA 15-3 test has low sensitivity (the percentage of time it gets a diagnosis correct). In fact, according to 2015 study from Germany, the CA 15-3 test has a sensitivity of only 55.6% when used to diagnose metastatic breast cancer.

Due to its potential for false-positive results, the American Society of Clinical Oncologists (ASCO) advises against the use of tumor marker tests to screen for new or recurring breast cancer.

Routine mammograms are still considered the frontline tool for breast cancer screening in most countries.

Risks and Contraindications

There are few risks associated with the CA-153 test. The test requires a blood draw, the procedure of which may cause mild pain, redness, or bruising. Lightheadedness and fainting may also occur. Infection is rare following a blood draw if standard health precautions are taken.

Less commonly, the blood draw may cause the leakage of blood beneath the skin, leading to the formation of a hematoma. Most hematomas go away on their own; larger ones may obstruct blood flow and require treatment.

Before the Test

The CA 15-3 is a blood test typically performed alongside a complete blood count (CBC), liver functions tests, and kidney function tests. There are no preparations needed for any of these tests.

Timing

The blood draw takes only a few minutes to perform. Factoring in registration and the waiting time, your appointment can take anywhere from 30 to 90 minutes to complete.

Location

The CA 15-3 test can often be performed at the oncologist's office during your visit. Alternately, you may be referred to a nearby lab.

What to Wear

You should choose a top that is either short-sleeved or has sleeves that can be easily rolled up. If you plan to return to work after the test, you may want to wear long sleeves to cover the bandage or puncture mark on your arm.

Food and Drink

There are no food or drink restrictions for the CA 15-3 test.

If you have small veins, it often helps to drink a couple of glasses of water before the test. Doing so won't affect the results but may plump your veins and make the blood draw easier.

Medication Use

Certain medications and supplements can interfere with the CA 15-3 test. Among them is biotin (also known as vitamin B7, vitamin B8, vitamin H, or coenzyme R). The CA 15-3 test relies on biotin to bind to the CA-153 antigen and may be affected if too much biotin is consumed.

While the recommended daily intake of biotin is unlikely to cause any harm, high-dose biotin supplements may trigger false-negative readings. Stop taking any supplement containing more than 0.03 milligrams of biotin 72 hours before the test.

In addition, the targeted cancer drug Afinitor (everolimus) may cause paradoxical effects. Because Afinitor can block the pathway by which CA-153 is expressed, the drug may cause CA 15-3 levels to rise when treatment is working (resulting in a false-positive result) or drop when treatment is failing (resulting in a false-negative result).

You should also advise the phlebotomist if you are on Afinitor so a notation can be made for the reviewing pathologist.

Cost and Health Insurance

The cost of a CA 15-3 test can vary by location but generally runs anywhere from $50 to $80 and sometimes more. If you have to pay out of pocket or have high copayment costs, it helps to shop around for the best price. Even if you do have insurance, check that the lab is an in-network provider; otherwise, your claim may be denied.

The test doesn't usually require preauthorization, but you may be limited as to how many you can take each year. Check your policy or call your health insurer for details.

If you are uninsured or struggling with treatment costs, ask your oncologist if there are any financial assistance programs you qualify for. You should also contact the Cancer Financial Assistance Coalition (CFAC), a group of national organizations that provide financial help to people with cancer.

What to Bring

You will need to bring a form of ID, your health insurance card, and either a credit card or check to cover any out-of-pocket expenses. Check which form of payment the office accepts in advance of your appointment.

During the Test

When you arrive at the lab, you will be asked to sign in and complete a registration form. Many labs will ask you to pay your coinsurance or copay costs in advance; others will bill you later. A consent form may also be provided, although consent is generally implied if you request a diagnostic procedure like a blood test.

The blood draw, also known venipuncture, is performed by a phlebotomist.

Throughout the Test

The phlebotomist begins by gently pressing his or her fingers against your skin to locate the best vein.

Once the vein is selected, they put on a pair of disposable gloves, place a tourniquet around your upper arm, and ask that you make a fist. You may be asked to pump your fist several times if your veins are small or "shy." The venipuncture site is then swabbed with an alcohol pad

You will feel a small prick as the needle is inserted. For the CA 15-3 test, the phlebotomist will need to obtain a minimum of 0.3 milliliters of blood, although more will be taken to allow for repeat tests. The vacuum-sealed test tube will usually have a red top or a gel barrier.

Once the needle is withdrawn, a cotton ball or gauze is placed on your arm until the bleeding stops. The phlebotomist then applies an adhesive bandage over the puncture wound.

Post-Test

You should be able to leave shortly after your test as long as you are not bleeding or feeling woozy. You can then continue your day as usual.

After the Test

You may feel sore or develop redness or bruising at the puncture site. These concerns will usually resolve on their own without treatment. If needed, you can take Tylenol (acetaminophen) to help alleviate the pain.

If you develop a small hematoma, you can apply a cold compress on your arm for 20 minutes several times a day to relieve the swelling. (Do not apply ice directly to the skin or leave it on for longer, as this may cause frostbite.) Larger hematomas or those that hardened may require splinting and compression.

Call your doctor if you develop any signs of infection after a blood draw, including a high fever and persistent or worsening pain, swelling, or tenderness at the puncture site.

Interpreting Results

The results of your test should be sent to your oncologist within three to five working days. The report will include a reference range outlining when the levels of CA 15-3 are normal or abnormal. The reference range is based on the expected values within a population and can vary slightly from one lab to the next.

Generally speaking, a CA 15-3 value of 30 units per millimeter (U/mL) or less is considered normal. With that being said, a single value is generally of less consequence that serial values (in which your results are routinely measured during the course of treatment).

For a CA 15-3 test to be truly qualitative, it must be evaluated in conjunction with a physical examination, diagnostic imaging, and other blood tests.

Higher CA 15-3 levels typically correspond with more advanced stages of breast cancer. The highest levels tend to be seen in metastatic breast cancer, particularly when the liver or bone is involved. However, CA 15-3 levels can be low or normal even in advanced disease since not all breast cancers produce CA 15-3.

On the flip side, CA 15-3 levels can be abnormally elevated during the first four to six weeks of a new cancer therapy. In the end, any treatment that disrupts a tumor can cause a transient rise in tumor markers. To avoid misinterpretation, the CA 15-3 test should be performed no less than two to three months after the start of a new treatment.

It is important to note that CA-153 levels may be elevated in people with benign conditions or no conditions at all. As opposed to cancer, these levels tend to remain stable. It is only when levels rise that further investigation may be warranted.

Follow-Up

If your CA 15-3 results are elevated, your oncologist will likely order additional tests. If the elevation is minimal, the doctor may take a watch-and-wait approach and simply order a repeat test several weeks later. Generally speaking, any increase of 25% or more warrants active investigation. This may include:

A Word From Verywell

The blood tests used to monitor metastatic breast disease can cause stress and anxiety, particularly if faced with a sudden rise in a tumor marker. However, it is important to remember that the CA 15-3 only provides only a small glimpse of what is truly going on—and it is only of value when examined in context to your health and other diagnostic evaluations. Having a transient rise does not inherently mean that cancer is spreading or invading other organs. Neither does a transient decrease mean that cancer is disappearing given that stage 4 cancer is not curable.

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