February 2018 Ask the Expert: Recurrence

February 2, 2018

At our November 2017 Breast Cancer 360, Keeping Cancer at Bay: What Researchers Are Learning About Recurrence; and our December 2017 webinar, Living With the Unknown: Coping With Fear of Recurrence, people who attended the programs had more questions than our experts had time to answer.

For February's Ask the Expert, Living Beyond Breast Cancer expert Angela DeMichele, MD, MSCE, who spoke at the Breast Cancer 360, answered questions we missed during those two programs, such as what role tumorinfo-icon cells play in recurrenceinfo-icon and what lifestyle changes can lower risk of recurrence.

We captured two short videos from our November 360 that offer the basics on two issues Dr. DeMichele discussed that night and about which she answered questions below. In the first video, Dr. DeMichele explains circulating tumor cells, or CTCs, and disseminated tumor cells, or DTCs. These are very tiny cells that can break off a breast cancer tumor and enter the bloodstream or find safe haven in the bone to fall asleep for a long time, sometimes forever. In the second video, Dr. DeMichele explains the steps to take part in SURMOUNT and CLEVER, clinicalinfo-icon trials that study how early-stage breast cancerinfo-icon recurs and treatments that may prevent metastasisinfo-icon. She reviews the medicines used in the CLEVER trial: hydroxychloroquine (Plaquenil) and everolimusinfo-icon (Afinitor).   

Remember: we cannot provide diagnoses, medical consultations or specific treatment recommendations. This service is designed for educational and informational purposes only. The information is general in nature. For specific healthcare questions or concerns, consult your healthcare providerinfo-icon because treatment varies with individual circumstances. The content is not intended in any way to substitute for professional counselinginfo-icon or medical advice.

You talked about disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) during the 360 on recurrence. For those who weren’t at the event, could you explain what they are?

Both are a type of cell that may put a patient at increased risk of recurrence. “Disseminated” refers to those in the bone marrow, “circulating” refers to those in the blood stream. It is thought that these cells arise from the original tumor in the breast, but are “dormant” or sleeping. They may or may not lead to a recurrence. This last point is critically important: DTCs and CTCs are NOT metastasis, and patients who have them are NOT considered stage IV or metastatic. These cells are linked to an increase in risk, like having positive lymph nodes or a high Oncotype DX score. But they do not guarantee a recurrence or metastasis. Patients may have these cells, but for some, the cells will never hurt them.

Are the disseminated tumor cells (DTCs) found during bone marrow aspiration, when a small amount of liquid tissue is removed to be examined, the same type as the patient’s original active cancer type?

We don’t yet know very much about these cells biologically in patients. But in animals, these cells appear to be quite different from the cells in the original tumor. They use different types of processes and mechanisms to work.

When do you anticipate that disseminated tumor cell (DTC) tests will become more readily available?

The tests for DTCs and CTCs  have been around for a long time. But until recently, we did not have the knowledge about how to potentially intervene, so their use has not been recommended. These tests are still most appropriately used in a research setting in which patients are closely monitored and offered the opportunity to participate in trials to treat them.

What are the side effects of the trial drugs?

All drugs have side effects, but the drugs we are using in our trials have relatively mild ones. The primary side effects are mild nausea, stomach upset, mild rash and occasionally mouth sores.

What are the risks of taking part in this trial?

There are numerous risks that patients must be aware of to participate. These range from the risk of side effects of the bone marrow procedure, to risks of side effects of the treatment, to the potential risk of emotional upset or distress upon learning that the cells are present and that the risk of recurrence may be higher than one thought.

Can you participate in the trial if you are currently taking an aromatase inhibitor?

Yes, patients who are taking an aromatase inhibitor, who meet the other eligibility requirements, may participate.

Can someone go on the trial if they are not near the University of Pennsylvania? What locations will be taking part in the more national trials in the spring?

The nationwide trial, called “GLACIER” will be conducted within the Translational Breast Cancer Research Consortium. The sites that will participate are in the process of signing on. It will be possible to see that list on the CancerTrials.gov site soon.

Are the tests and drugs for people in this trial only for hormone receptor-positive breast cancer, or for triple-negative breast cancers, too?

The trial allows for patients with all subtypes of breast cancer to participate. We believe that there are common mechanisms that these cells use to survive and thrive that are not dependent on the subtype.

Is there a screening for metastatic disease required before you can enroll in the trial?


What percentage of patients who get tested have dormant tumor cells?

The frequency of positive cells in our trial is approximately 20 percent. But it is important to remember that this number will vary depending on the type of patients that we are screening. We are still learning about the rate of positivity within different groups.

How many years past treatment are you eligible to take part in the trial?

Within the first 5 years after diagnosis.

How accurate are disseminated tumor cell (DTC) and circulating tumor cell (CTC) tests? What’s the chance you would miss existing DTC and CTCs with these tests?

This is an excellent question, and one that we are trying to answer in our studies. The false positive/false negative rate is not known. There have not been any studies done to date to assess this. But we do suspect that the test is not as accurate as we would like, because the cells are so rare. We are developing a more sophisticated and sensitive test that we hope will be more accurate than the current test.

Is it worse to have disseminated tumor cells (DTCs) or circulating tumor cells (CTCs)?

Another excellent question, to which we do not yet have an answer!

Is there a relationship between having cancer in the lymph nodes and the chances of having dormant tumor cells or circulating tumor cells? If you don’t have a pathological complete response, are you more likely to have disseminated tumor cells (DTCs) or circulating tumor cells (CTCs)?

We believe that other risk factors for recurrence will be related to these cells, but the studies to date suggest that these cells can be present independent of the other risk factors.

Does having hormone receptor-positive breast cancer increase the likelihood of having circulating tumor cells (CTCs) or disseminated tumor cells (DTCs)?

We do not yet have the answer to that question. Our studies seek to find that information.

What is the likelihood of having disseminated tumor cells (DTCs) if you had a pathologic complete response?

The largest study that has looked at this suggests that the rate is low – probably less than 5 percent. 

What is the difference between metastasis and recurrence?

These are very similar terms, almost interchangeable. A recurrence simply refers to the reappearance of breast cancer after a patient has already had the diagnosis. This could be in the breast, in the chest wall, in lymph nodes or somewhere else in the body. We typically use the word “metastasis” when the recurrence is found at a distance from the original tumor in the breast, outside the breast and lymph nodes.

What percentage of breast cancer patients suffer a recurrence?

We currently estimate that up to 30 percent of patients will experience a recurrence in the course of their lifetimes.

Is there any research on preventing metastasis in someone who has had a local or regional recurrence?

Yes, there are many studies looking at local therapies such as different types of radiation.

Are there any trials on how tumor cells travel and cause metastasis?

The studies we and others are conducting are designed to help us understand the process from start to finish. For example, we are investigating how the cells get out of the breast, what enables them to find and thrive in the bone marrow, how they remain “dormant” or sleeping, for many years, and what methods they use to wake up, travel elsewhere and become a metastasis.

Outside of the tests mentioned for dormant tumor cells, what other screening tools are recommended for women diagnosed with breast cancer in their 20s and 30s?

We refer to the monitoring of patients who have had breast cancer as “surveillance” rather than “screening.” “Screening” is a term typically used to refer to the monitoring of women who have never had the disease. Current recommended surveillance includes a yearly mammogram and follow-up every 6 months for the first 5 years after diagnosis. For women who have hereditary risk factors, breast MRI is also added. Importantly, we currently do not recommend scans such as CT scans or PET scans, and we do not recommend blood tests for tumor markers, such as CA 15-3 or CA 27-29, as these do not appear to improve outcomes.

How can I monitor whether cancer has returned?

At this time, the best way to monitor this is to be attuned to any changes in how you are feeling, and report them to your doctor. My rule of thumb is to recommend that patients contact me for any new, persistent or worsening symptom that lasts longer than a week or is not improving with over-the-counter remedies such as Tylenol or Motrin. Of course, the vast majority of these symptoms do not turn out to be a recurrence, but such symptoms will prompt your doctor to investigate further and rule out this possibility.

Am I more likely to have a recurrence because I had HER2-positive breast cancer, even though I had a year of trastuzumab (Herceptin)?

It is difficult to answer this question. Many factors go into calculating a patient’s individual risk. HER2-positivity is not always linked to greater risk than other types of breast cancer. And taking trastuzumab will reduce the risk associated with HER2-positive disease. 

Are there any dietary (or other) suggestions specific to prevent breast cancer recurrence?

Currently, the only dietary data we have suggest that a low-fat, low-calorie, high-fiber diet is best. However, it is hard to really say whether there are specific things about diet that reduce recurrence.

 Overall, the best data suggest that there are several lifestyle guidelines to follow to minimize the risk of recurrence:

  • Keep body mass index lower than 25
  • Limit alcohol intake as much as possible, and to no more than two drinks per week
  • Get regular exercise
  • Replenish vitamin D levels

One additional piece of information: The data on soy in estrogen receptor-positive disease is controversial. However, I believe that the plant estrogens in soy-based foods and other foods containing plant estrogens may be harmful and should be minimized.

Does research show tamoxifen and aromatase inhibitors stop working after a certain period of time? I am on anastrozole and into my 6th year. At the end of 10 years, what will happen? When I stop, will I get cancer again?

The benefits of these drugs extend beyond the time you stop taking them. However, even with the drugs, there will be a small lifetime risk of the cancer coming back. This risk persists when you have completed taking them.

Can you talk about capecitabine (Xeloda) for preventing recurrence in early-stage triple-negative breast cancer in people who don’t have a pathologic complete response to neoadjuvant chemotherapy?

There was a randomized trial of capecitabine (Xeloda) that showed that women without a pathological compete response who took this drug for 6 months had a 30 percent lower risk of recurrence than those who did not. This trial was conducted in Asia. These results have not been seen with other trials of capecitabine. But because the results were so impressive, this treatment has become part of the conversation for patients who do not have a pathologic complete response.  

There’s lots of discussion about 5-year survival rates. What are the rates for recurrences that occur 10, 15 or 20 years later? Are they related to young age?

We now do have data for women who are more than 10 years out from a large study called the “overview” analysis. This suggests that some patients will continue to relapse at a very low rate (less than 2 percent per year) beyond 10 years. This is most likely to happen in patients who have had estrogen receptor-positive breast cancer and is rare in those with HER2-positive or triple-negative disease.  

Is there a supplement that all breast cancer patients should take [to prevent recurrence]? Is it something that should be individually tailored to each patient?

Unfortunately, there are no data on specific supplements that help breast cancer patients. It is important to recognize that many are safe but some can be harmful. I recommend letting your doctor know about any supplements you are taking. It is also helpful to seek the advice of a complementary or alternative medicine practitioner who can make sure you are taking things that are helpful (for symptoms, for example) and not harmful.

I had a lump under my left arm pit and they took out nine nodes with one being cancerous. I now get my left arm and elbow hurting off and on. I am afraid it is bone cancer but all doctors blow it off as nothing. Do I have any reason for my fear?

It is very common to have residual pain in the arm after the type of surgery you had. However, if you are worried and do not think you are being taken seriously, it is always helpful to get a second opinion. If the answer is still “no cancer” then a physical therapist may be helpful to you in managing your symptoms.

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