Understanding No Evidence of Disease (NED) in Breast Cancer

What this designation means long term

road sign which says "surviving cancer"
What exactly does it mean to be NED - no evidence of disease?. Istockphoto.com/Stock Photo©MCCAIG

The term no evidence of disease (NED) is often used with cancer when there is no physical evidence of the disease on examination or imaging tests after treatment. No evidence of disease means the same thing as complete remission or complete response. It does not, however, mean that a cancer is cured. With most cancers, there is a chance it could recur at a later date.

Certainly, "being NED," as some often call it, is very positive, as it means that treatment was effective. Since the recurrence of cancer and metastases (when cancer spreads to other sites in the body) are responsible for the majority of cancer deaths, there is currently a lot of research focusing on how to keep a cancer in a state of NED.

It's also important to note that people with cancer who are NED need tremendous support. Not only do many people who have achieved a complete remission need to cope with the fear of recurrence and potential survivor guilt, but late effects of cancer treatment can sometimes reduce quality of life.

Levels of Disease

The National Cancer Institute defines remission as a “decrease in or disappearance of signs and symptoms of cancer." Remission is further categorized as either partial remission (when only some of the signs and symptoms of disease have disappeared) or complete remission (when all are gone, but cancer may still remain).

The latter applies to NED. It describes a point in time when you have no signs or symptoms of cancer, nor any evidence of cancer on blood tests, such as tumor marker tests, or imaging studies, including computed tomography (CT), magnetic resonance imaging (MRI), bone scans, or positron emission tomography (PET). NED may be temporary, as cancer could still be lurking. But it could also be permanent.

People may be NED after an early-stage cancer is treated. They may even be NED with metastatic cancer (see below), though the disease will almost inevitably recur at some time in these cases.

It's possible for breast cancers, especially estrogen-receptor positive tumors, to recur many years, even decades after they appear to have been eradicated.

NED in Metastatic Breast Cancer

Metastatic breast cancer (MBC) requires treatment to control the disease for the rest of a person’s life. Metastatic disease with NED is associated with longer survival compared to metastatic cases that never gets this designation.

A study published in 2015 looked at 570 MBC patients who were treated from January 2003 to December 2005. It found that 16% (90 patients) achieved NED, which the researchers defined as a “complete metabolic response” and “healing of bone metastases” seen on PET scans and MRIs. NED status, they noted, "significantly prolonged survival." The three- and five-year overall survival rates for the NED patients were 44% and 24%, respectively.

The researchers determined HER2 positivity was a strong factor associated with overall survival, and estrogen-receptor positivity was significantly connected to progression‐free survival.

Interestingly, one drug in particular seemed to be connected to progression-free survival: Herceptin (trastuzumab), a medication often used in cancers that are HER2-positive.

Why Doctors Don't Say Cancer Is "Cured"

Doctors rarely use the term cure when talking about solid tumors—even if there is a 99% likelihood a cancer will never come back. It is impossible to know if there are micrometastases present in your body—that is, areas of cancer spread that are too small to be seen on imaging studies.

For now, with some exceptions from doctor to doctor, it's likely that the word cure will mostly remain reserved for only the smallest pre-cancers and some childhood blood-related cancers.

Durable Response

Some people with stage 4 cancer who have been treated with immunotherapy drugs appear to have what is being called a "durable response." Unlike treatments such as chemotherapy, the benefits of some immunotherapy drugs persist after treatment has stopped. It will be some time before experts know whether or not these drugs are actually curing some people with advanced cancer.

Recurrence

Researchers know how breast cancer spreads, but they don't know exactly why some cancers return years later. There are theories that describe dormant cells or stem cells having the ability to hide and evade treatment. With the recommendation of a new treatment options for some people with early-stage breast comes a slightly better understanding of this.

For women who have early-stage postmenopausal estrogen receptor-positive breast cancer, the bisphosphonate medication Zometa (zoledronic acid) is now recommended as adjuvant therapy. This medication, which has been used for osteoporosis and bone metastases, appears to affect the microenvironment in bone (i.e., the tissue surrounding a cancer), reducing the risk of bone metastases.

Such findings have led researchers to question whether dormant breast cancer cells (with NED) stay in the bone marrow.

One 2018 study shows certain protein markers indicate if a person will develop a recurrence of lethal, metastatic breast cancer. When cells from the original breast cancer tumor metastasize into the patient’s bone marrow, either with no or only a small amount of the protein NR2F1, the patient eventually died. However, the patients who had high concentrations of NR2F1 in their bone marrow did not frequently develop metastatic breast cancer and lived longer.

Researchers believe NR2F1 promoted dormancy in cancer cells, eventually deactivating them, thus improving survival and decreasing the risk for recurrence. 

You may wonder why you aren't scheduled for regular imaging exams, including PET scans, as with other cancers. The reason is that even though these scans may show a recurrence slightly earlier than would be possible based on symptoms alone, there is no evidence that survival is improved by detecting signs of a recurrence before any symptoms are present.

Concerns

Being NED, of course, is a good thing. Still, many people deal with a variety of feelings in this new phase of their cancer journey—especially if it seems like those around you are going back to life as usual, but you are coping lingering side effects, "what ifs," and other concerns.

If can help to have a sense of what you might encounter and to reach out to local or online support groups that have members going through the same thing. If your feelings become too overwhelming, seeking the help of a therapist may be beneficial.

Late Effects of Cancer Treatment

The majority of people who are NED are still coping with some side effects from the treatments it took to get to NED. Symptoms, such as cancer fatigue, pain, hot flashes, and more, linger far past the last dose of chemotherapy or radiation.

Continue to be in contact with your doctors if any symptoms are lingering or if any new ones arise. You are definitely not the first to encounter them, and your medical team is a great resource for helpful strategies.

Fear of Recurrence

The fear of recurrence is very real whether you had a very early-stage cancer or an advanced one. Life is much different than before cancer. What you once would have considered a mild headache may cause you to fear that cancer is reappearing in your brain. A tickle in your throat from seasonal allergies may prompt worry that cancer has returned in your lungs. There's also the natural feeling about overcoming any type of adversity—I can't get too comfortable with my new reality because it may not last.

Fear of recurrence is universal. Some people find it helpful to talk with an oncology counselor to develop ways to best cope with this.

Survivor Guilt

People are often surprised to realize the mortality rate from breast cancer really hasn't changed that much. Certainly, the treatment options for early-stage disease are reducing the risk of recurrence, but recurrences still occur.

If you are NED, you may think, Why me and not someone else? This can especially creep into your mind if you know others who have not survived the disease or who have stage 4 breast cancer, for which there is no longer a possibility of a cure.

This can come up in a variety of settings and relationships. Surrounding yourself with others who have had cancer can give you much-needed support, but it also means you may lose friends.

It's important to acknowledge how you're feeling—and to get to a place where you can accept that there is no answer to Why?

Life Being NED

It may help to look into a survivorship program to help you get the psychological and medical support you need. Your oncologist likely has more information about locating such a program.

In addition, these lifestyle strategies can help you in this new chapter:

  • Enjoy a healthy lifestyle: There is some evidence that eating a healthy diet, as well as exercising regularly, may lower the risk of recurrence.
  • Get enough sleep: If you suffer from sleep difficulties, talk to your doctor. Some studies suggest that breast cancer may be more likely to recur in women who suffer from insomnia.
  • Find ways to reduce stress: Much like insomnia, it has been suggested that stress can play a role in some people going from NED to recurrence.
  • Journaling: There are many benefits to journaling, including stress relief, clarifying thoughts, chronicling your journey, and even making sense of everything that has happened to help you let go.

A Word From Verywell

NED is a milestone for certain. It's one you undoubtedly wish you never were in the position to have to reach in the first place, but a welcome one worth now celebrating. If you get overwhelmed by all you've been through and the possibilities of what could happen, that is understandable. However, while you've faced challenges, think of all you have gained from your experience (e.g., courage, perspective, and so on). While everyone is different, many survivors say that their disease led to personal growth.

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