Monitoring Response to Metastatic Cancer Treatment

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As you go through metastatic breast cancer treatment, your doctor will order many tests to see if your cancer has progressed or if it is responding to treatment. What tests are usually done, and how can you cope with the anxiety testing brings?

Some of these imaging studies and lab tests are used both when someone is diagnosed with early-stage or metastatic breast cancer, whereas others may be new to you as they are primarily used to monitor the treatment of metastatic breast cancer.

How Tumors Can Change

We often think of cancers as unchanging, like the normal cells in our breasts which do not change significantly over time. Yet cancers are always changing. It is this change in tumors, in fact, which accounts for the resistance we see to treatments such as hormonal therapies, targeted therapies, and chemotherapy over time.

The molecular characteristics of a tumor can change, as well as the receptor status of tumor cells. Cancers are continually adapting to their surroundings, often producing new proteins to evade our immune systems and altering their appearance to aid their survival.

A tumor may have been estrogen sensitive when you were first diagnosed, but it may be estrogen receptor negative when it reappears in your lung. A tumor may be HER 2 positive when first diagnosed, but HER 2 negative later. These changes are common, with up to five percent of HER 2 positive tumors becoming HER 2 negative later on.

In addition to changes in tumors is the concept of tumor heterogenicity. Rather than being a mass of all identical cells, different parts of a tumor may have different characteristics than others, depending on these changes. Sometimes one portion of a tumor over-expresses HER 2, while another section of a tumor, or a metastasis in a different location, does not.

This is a simplistic description of what happens, but may help explain how every breast cancer is unique.

Biopsies

One of the most important first tests is a biopsy of your cancer. One reason your doctor wants to biopsy your tumor is to make sure that it is metastatic breast cancer rather than an unrelated tumor. Yet the most important reason for a biopsy, or a “re-biopsy,” is to determine how your cancer may have changed since the time you were first diagnosed.

Imaging Studies

The imaging scans your doctor recommends will depend on many things from the location of your tumors to the treatments used. Common tests (as discussed earlier) include:

  • X-rays of areas in which you’re suspected of having bone metastases
  • Bone scans: A bone scan involves injecting a radioactive tracer, which is then evaluated with imaging. Bone scans can be helpful in evaluating bone metastases.
  • PET scans:  A PET scan is an important test for determining the extent and locations of metastases in your body. Unlike CT scans and MRI scans which look primarily at structural features, a PET scan looks at the function of cells in your body. Radioactive sugar is injected into your bloodstream and is taken up by actively growing tissues such as cancer cells. Imaging studies can then allow radiologists to visualize and locate these areas in the body. In addition to helping to evaluate the extent of your cancer, PET scans are helpful in distinguishing areas such as scar tissue and fibrosis from actively growing malignant tumors.
  • CT scans: A CT scan may be done to look at your abdomen, your pelvis, your chest, or your head
  • MRIs: MRIs may be done to get a more accurate look at any metastases in your brain or other regions of your body.

It’s helpful to share a few things about imaging tests and their limitations in following cancer which have confused others with metastatic breast cancer:

  • Changes on a scan can be delayed – If you just finished a treatment such as chemotherapy, you may feel discouraged if a scan of your cancer hasn’t changed in size. It’s helpful to understand that changes on an imaging test can take time to show up. For example, a decrease in tumor size due to treatment may not show on a scan until a few weeks or even months after your treatment is completed.
  • Scans aren’t perfect – No matter what type of scan you have, there is a chance it will “find” something that would otherwise not be a problem. The more tests you have, the more likely this is to occur. An example includes the many benign liver nodules found on abdominal CT scans that can be hard to distinguish from cancer.
  • Scans other than PET scans can’t tell you if a “spot” is “growing” – It may be difficult on a test such as a CT scan to determine if a “spot” represents a cancer which is growing, or simply scar tissue left over after an area of cancer has been treated. PET scans can help distinguish actively growing cancers from benign processes, but can also have “false positives” – areas of concern which turn out to be nothing.
  • A small change in the size of a tumor may be meaningless – Some people become discouraged if a tumor appears to be a centimeter larger on a scan than it had been on a previous scan. If you are faced with something like this, ask your radiologist about the limitations of the particular scan you had. In some cases, a tumor which may “appear” to be larger or smaller, may actually be unchanged in size if you were able to measure the cancer directly.

Tumor Markers (Biomarkers)

Tumor markers or biomarkers are proteins which are either secreted by a tumor or by the body in response to a tumor. Blood tests to check for these proteins may be done to follow your progress with metastatic breast cancer.

As with imaging tests, these tests are not perfect. Not all breast cancers cause elevations in these biomarkers, and when they are elevated, it may be due to a condition other than cancer. A change in the levels of these markers, just as with scans, can be delayed by several weeks after a tumor increases or decreases in size.

These tests are rarely used alone to monitor the progress of a breast cancer and are most helpful when the levels are followed over time. Tumor markers your doctor may measure include:

  • Cancer antigen 15-3 (CA 15-3) - CA 15-3 is a protein made by breast cancer cells. It can be found in 50 to 90 percent of people with metastatic breast cancer, but only 30 percent of people with early-stage breast cancer. Levels of this biomarker tend to be particularly high in those who have bone or liver metastases. CA 15-3 may be measured to assess the response of your cancer to treatment, but a change in the level may not occur for several weeks (often four to six) after a tumor either responds to treatments or progresses.
  • Cancer antigen 27.29 (CA 27.29) - CA 27.29 is a protein (a monoclonal antibody) that is produced by a gene known as MUC-1. This protein is found on the surface of some breast cancer cells. In contrast to the other markers, CA 27.29 is the only protein which specifically indicates the presence of breast cancer cells. Though this test is not currently used to monitor women with early-stage breast cancers for a recurrence, it’s thought that an elevation may occur around five months before a person is otherwise aware that their cancer has recurred. As with CA 15-3, there are conditions other than breast cancer which can cause elevations in this protein, and elevations may remain for a significant amount of time (two to three months) even after a cancer has been effectively treated. Your doctor may order either a CA 15-3 or CA 27.29, but not usually both.
  • Carcinoembryonic antigen (CEA)CEA is a nonspecific protein which may be elevated in people with cancer, but may be elevated in response to several other conditions as well, including smoking.
  • Circulating tumor cells – Monitoring blood for circulating tumor cells (tumor cells or parts of tumor cells which have broken off from a tumor and entered the bloodstream) is a newer approach for evaluating and following metastatic cancer. Though still mostly investigative, one test has now been approved for use in women with metastatic breast cancer.

Coping With Scanxiety

Most people will feel some level of anxious while waiting for the results of a scans or laboratory test, regardless of at what point in the treatment it was performed. With metastatic breast cancer, in particular, there are many test results to await.

You’re not alone if your mind develops and mulls over frightening scenarios of what the results can be—and more importantly, what they mean.

You can do several things to cope with the "scanxiety."

  • Ask about the timing of your results and how you'll be receiving them.
  • Be picky about the timing of your scan. If it's earlier in the day it might get read by the end of the day, saving you stress overnight. Earlier in the week might mean saving stress over the weekend.
  • Ask somebody to join you when you go to the exam, as a distraction.
  • Laugh. Watch a favorite funny movie, go to a comedy show, or try anything that will make you smile.

Sources:

Graham, L., Shupe, M., Schneble, E. et al. Current Approaches and Challenges in Monitoring Treatment Responses in Breast Cancer. Journal of Cancer. 2014. 5(1):58-68.

 

DeVita, Vincent., et al. Cancer: Principles & Practice of Oncology. Cancer of the Breast. Wolters Kluwer, 2016.

Liedtke, C., and H. Kolberg. Systemic Therapy of Advanced/Metastatic Breast Cancer—Current Evidence and Future ConceptsBreast Care. 2016. 11(4):275-281.

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