Revolution in breast screening on the cards

 

Results of research in Galway could lead to a simple blood test for breast cancer, writes DR MUIRIS HOUSTON

IT IS the lot of the medical journalist to read hundreds of research papers every year. Most are interesting but at best nudge science forward. Very occasionally you read something that makes you sit up and think: “Hmm, that’s interesting.” And then there is the extremely rare paper that sends a shiver down your spine, such is its potential impact on a particular branch of medicine.

The term paradigm shift may have been overused in the past, but it is fair to associate it with the groundbreaking research into breast cancer that has just emerged from the Department of Surgery at NUI Galway. Not alone does the newly-discovered blood test have the potential to more accurately assess how a woman with breast cancer responds to current treatment, but it may, subject to further research, replace mammography as the main screening method for breast cancer.

For the first time, the Galway researchers, led by Michael Kerin, professor of surgery at NUIG, have measured substances called microRNAs (miRNAs) in the blood of patients with breast cancer. Their work found a link between specific types of miRNAs and the presence of breast cancer. In addition, the research team showed that the blood levels of a novel tumour marker dropped sharply within two weeks of surgery for a breast tumour, an indication of the sensitivity of miRNAs as a measure of successful cancer treatment.

They have found that a combination of mir195 and Let7a (two specific types of microRNA) are sensitive markers for the presence of breast cancers in over 90 per cent of cases.

MicroRNAs are tiny fragments of genetic code, which until recently had been considered of little relevance in the process whereby specific genes give a signal to produce different proteins in the body. Now, however, they are known to be highly important as both suppressors and promoters of cancer growth, with both mir195 and Let7a powerful players in the development and propagation of breast cancer.

Although medicine has come a long way in the management of breast cancer in recent years, existing diagnostic tools and bio- markers for breast cancer have some deficiencies.

Mammography is currently the gold standard diagnostic tool and is the basis for national breast cancer screening programmes. But it is not perfect; it involves exposure to radiation and some 8 to 10 per cent of women who have the test, but who don’t have cancer, will be told initially they do have a tumour.

Biomarkers are substances that can tell doctors additional information about the nature of different cancer types. Currently just two markers are established in the routine evaluation of breast tumours: ER (oestrogen receptors), the presence of which indicate the cancer will respond to endocrine treatment such as tamoxifen; and HER2/neu which predicts a good response to a particular chemotherapy agent.

A number of circulating tumour markers such as carcinoembryonic antigen and carbohydrate antigen 15-3 are widely used in the management of breast cancer, but the sensitivity of these markers is low, and so they are not useful as screening tools.

The ideal test for breast cancer should be easily accessible: it could be sampled in a minimally invasive way; must be sensitive enough to detect the early presence of tumours in almost all patients who have the disease; and should be absent, or at very low levels, in women who are cancer-free.

How might microRNA live up to these criteria? As short RNA molecules that regulate gene expression across a wide spectrum of biological and pathological processes, an important feature of miRNAs is their remarkable stability. They are known to be well preserved in tissue samples even after years of chemical preservation. But where the Galway researchers have hit the jackpot is their development of a reliable way of measuring miRNA in blood. And not just that – they have shown how sensitive these blood levels are in reflecting how active a particular breast cancer might be.

The finding that levels of specific miRNA drops sharply within two weeks of the successful removal of a breast tumour is further proof of the quality of the new test. In addition, the test works as a simple blood test, one of the least invasive ways to check for disease in the human body. Although the patient numbers in this initial research are low, the study is statistically robust. Preliminary analysis suggests that a combination of the Mir195 and Let7a measurement in blood will be 92 per cent accurate in detecting the presence of breast cancer in women who have yet to develop symptoms.

If this finding is replicated in larger studies, there is a real possibility of breast cancer screening taking place in your local surgery, using nothing more complicated than a blood test.