Biomarkers in metastatic breast cancer: Do they make a difference?


When it comes to our health and our health care, we love the numbers. Sometimes, we even fall in love with the numbers, assuming that the numbers tell us the whole story when, in fact, that may not be the case. Cholesterol numbers, blood pressure numbers, body mass index, whatever. As patients and consumers, we are frequently defined by our numbers.

But what happens when those numbers and other medical tests, such as CT scans, really don’t tell the story we think they do? The recent evolution of prostate-specific antigen (PSA) is a case in point. For decades, we believed the numbers saved many lives. It turns out, PSA did save some lives, but not as many as we thought and at the considerable financial and human expense of treating many men who probably did not benefit.

So in that vein, an article and editorial in a recent issue of the Journal of Clinical Oncology makes the point that just because we have numbers, it does not really mean they offer us the scientific certainty about the course of cancer we may think they do.

The research reviews the use of various biomarkers (called serum tumor markers or STMs) and imaging tests (CT and PET scans) in women with metastatic breast cancer. The researchers looked at Medicare data from 2002 and 2011 to find women who received more than 12 blood tests with biomarkers (CEA, CA 15-3, CA 27.29) and/or more than four CTs and/or PET scans in a 12-month period and compared outcomes with women who received fewer tests over that same period of time. Their goal was to determine whether those who had more testing did better than those who had fewer tests.

It turns out about 40% of the women older than 65 with metastatic breast cancer had both the blood tests and imaging studies done periodically to monitor the progress of their disease. Of this group, about 1 in 3 had the status of their breast cancer monitored very frequently during the 12-month segments. The annual costs of treating those who were tested frequently was almost 60% more than the cost of treating compared women with the same illness but who didn’t have all those studies.

All this would be irrelevant if frequent testing led to improved quality and/or years of life. But the authors found no such thing. Overall survival was not improved by frequent disease monitoring. Moreover, they point out there aren’t any generally accepted guidelines that tell health professionals which tests to order and how frequently they should be done, so we really don’t know the right answer to how often these tests are necessary.

The conclusion?

From the authors:

Currently, in the metastatic setting, there is no evidence to suggest that more frequent testing is associated with better outcomes … Furthermore, in women with early-stage breast cancer, surveillance testing, which can result in earlier treatment initiation, does not affect survival.

The editorial that accompanied the research report essentially agreed with the report’s authors:

Despite its availability for more than two decades and provision of prognostic information, no evidence indicates that STM (serum tumor markers) monitoring changes the course of the disease. Since 1999, ASCO (American Society of Clinical Oncology) has recommended explicitly against STM use for surveillance after treatment of early-stage breast cancer, yet 42% of Medicare-age breast cancer survivors undergo STM assessment an average of almost three times a year, which results in 20% higher medical costs with no known impact on survival. Similarly, ASCO has recommended against the routine use of STMS in MBC (metastatic breast cancer) in the absence of other measureable disease since 2006, with all subsequent updates confirming this initial guideline.

This appears to be a lesson we keep on learning: we have tests, we do tests, we think tests help us make better decisions by “staying on top” of someone’s cancer and sometimes we find out — when the evidence is finally looked at carefully — that the tests really don’t make a difference.

No one likes to think of costs when it comes to medical care, especially when saving lives. But while a lab test or an imaging study may not make a difference to our care or the outcome of our illness, it certainly does make a difference to our pocketbook. And even worse, it may give us a false sense of comfort when it doesn’t accurately reflect a change in our disease or sends us down another, perhaps, more toxic path of treatment when it wouldn’t make a difference to do so.

Those are all very serious questions that must be answered.

Many years ago we routinely did bone scans to follow women diagnosed and treated for primary breast cancer. We firmly believed that if we found a new bone lesion early and started therapy immediately at the first evidence the disease had recurred and spread, we would save lives. We were wrong. The evidence showed us it didn’t make a difference, so we stopped doing the test.

Years later, we are still learning the same lessons. Sometimes doing lots of tests makes all of us feel better. It helps us feel in control. It helps us feel that we are going to be able to change the course of our illness and treatment at the earliest moment and, as a result, improve our outcome. But despite all of those considerations, we need to look at the evidence and understand that sometimes that just is not the case.

There are no easy answers to these questions. Health professionals and patients have their own thoughts and their own expectations, and there is no question that each personal situation is different sometimes requiring stepping outside the guidelines or currently accepted practice.

However, even understanding that consideration, we also need to realize that just because we can do something doesn’t mean we should, or that it really makes a difference. We need to look at the evidence, we need to understand the evidence, we need to listen to the evidence and let that be our guide — especially and most importantly when the message the evidence offers differs from what we think we already know.

Easy to say, difficult to do. It is a lesson we keep on learning. Maybe it’s time we paid attention to the message.

J. Leonard Lichtenfeld is deputy chief medical officer, American Cancer Society. He blogs at Dr. Len’s Cancer Blog.

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