Biomarkers: How good a cancer test are they?

Cancer biomarkers have changed the way we detect and treat the disease. But are they all they're cracked up to be?
Breast cancer drug Herceptin
Herceptin targets breast cancer via the biomarker HER-2, which was discovered in the 80s. Photograph: Time Life Pictures/Getty Images Time Life Pictures/Getty

Barely a week goes by without headlines blaring some new way of understanding, detecting or treating cancer. It could be a newly identified gene or a protein in the blood, yet finding these biological fingerprints, known as biomarkers, is a valuable and rapidly growing part of medical research, with enormous potential for improving health.

But is that potential all it's cracked up to be? Of the thousands of known biomarkers (and counting), only a handful have actually made it into the clinic. Writing last week in the Journal of the National Cancer Institute, Eleftherios Diamandis of Mount Sinai Hospital in Toronto, Canada, points out that "no new major cancer biomarker has been approved for clinical use for at least 25 years".

There have been successes for sure. One of the more famous biomarkers is the protein HER-2, which is the target of the breast-cancer drug Herceptin. HER-2, first discovered in the early 80s, can be found on some breast tissues and an excess of this protein is found in some forms of breast cancer. Herceptin can act against HER-2 and, by looking for this biomarker in a patient, doctors can work out who might benefit from Herceptin treatment. Another example, the Philadelphia chromosome that results from movement of DNA from one site on the human genome to another, is a marker for chronic myeloid leukaemia.

But not every biomarker is as useful. For a while, scientists got excited at the possibility of measuring levels of prostate-specific antigen (PSA) as a way of screening prostate cancer. But they now know that PSA levels are also raised in non-cancerous enlarged prostates, making a reliable diagnosis more difficult. There are several other examples of failed cancer markers, such as lysophosphatidic acid and osteopontin for diagnosing ovarian cancer.

So what's the problem with these biological fingerprints? Why are they proving difficult to use?

Diamandis highlights several issues. One is that many of the molecules being discovered are not specific to a single cancer. Levels of a protein called alpha-fetoprotein increase in liver cancer, but can also rise in testicular or ovarian cancers. Another protein, carcinoembryonic antigen, increases in colorectal and pancreatic cancers, but is also raised by smoking.

The tests used to measure biomarkers may themselves be problematic too. The test may tell a patient that they have cancer when they don't, or miss a cancer. Incorrect tests can cause huge anxiety for patients, who might spend anguished days wrongly thinking they have a serious disease, or be reassured by a falsely negative test result.

It might also be be that the amount of a chemical released by the cancer is too low to be detected by current tools.

It sounds a bit depressing. But don't give up on the idea of biomarkers just yet.

Adrian Ibrahim, associate director of Cancer Research Technology at Cancer Research UK, says: "As new technologies are developed ... we hope to see the development of more promising cancer screening markers."

When it comes to using biomarkers for diagnosis and treatment of cancers, they can help the process, but they can't always act in isolation. Clinical judgment is important too.

And the presence of a biomarker doesn't necessarily mean that you will develop the cancer. If you have the BRCA-1 or BRCA-2 gene, for example, there is a 55% to 85% chance that you might develop breast cancer in your lifetime – by no means an inevitability.

Other factors include lifestyle. Smoking and diet will interact with genes to increase or decrease your chances of developing a cancer, for example. As will the place you live and a myriad other environmental conditions that can interact with and modify the outcomes from your genes.

So Diamandis urges caution. "Just because it's in print doesn't mean it is true," he says. Cancer biomarkers have changed the way in which we manage the disease and will continue to do so but are not the whole answer. Carry on reading those headlines, but do it with lots of pinches of salt.

Monica Desai is a British Science Association media fellow