Can a simple blood test really predict breast cancer?BMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e3374 (Published 15 May 2012) Cite this as: BMJ 2012;344:e3374
- Margaret McCartney, general practitioner, Glasgow
The Radio 4 Today programme heralded a day of wall to wall epigenetics. “Every now and then a new word emerges from scientific journals that lay people have to get used to. Such a word is epigenetics,” said presenter John Humphrys. Changes within genes resulting from environmental factors that may be linked to breast cancer “may be able to be detected early, many years before the cancer develops,” he explained.
James Flanagan, the corresponding author of the study under discussion, was asked about the implications and agreed that it was a breakthrough. “We’ve found something that we can detect before breast cancer develops, so as a risk marker, this is really what we want to find.” People with a high level of abnormalities are at high risk.
Humphrys asked, “So you’re going to be able, potentially, fairly soon, to be able to assess the level of risk and thereby take precautions; an individual can be screened regularly or whatever.” Flanagan replied, “Yes, this is the hope.” He expressed a further hope that more genetic markers could be found, and that women could have their risk stratified. He expects that epigenetics research will lead to more blood testing for “early detection” of breast cancer, with an expectation that molecular risk profiles will be available in five to 10 years, “which would be quite simple and therefore quite cheap . . . It would be groundbreaking, because it will decrease the incidence of breast cancer and thereby the mortality.”1
But is it really so simple? The paper, published in the journal Cancer Research, was titled “Intragenic ATM methylation in peripheral blood DNA as a biomarker of breast cancer risk.”2 It describes three cohort studies, one of which was of women at high familial risk of breast cancer, and DNA methylation at specific loci on white blood cells.
For one set of statistically significant results, in women aged 21-49, 90 out of 258 women were in the highest quintile for methylation and developed breast cancer, compared with 39 out of 217 of controls—that is, 35% versus 18%. This is, therefore, far from a definitive test, with a substantive risk of false positives, and it does not follow that there are effective prophylactic treatments that can then be given. Far from finding a simple blood test that could decrease mortality, this would come with considerable uncertainties attached.
Delyth Morgan is chief executive of the Breast Cancer Campaign. For a seemingly obscure study, it scored top media coverage. “I was really pleased,” she said. “I remember years ago debating how to encourage the public to engage with science more. We need the public to understand risk, and a lot of the coverage was about risk, which I thought was really interesting.” The charity wants to remind people that age is the biggest risk factor for breast cancer and remind them about modifiable lifestyle factors. But is it worth presenting research as straightforwardly good when the implications are likely to be complex? “The challenge for charities is always to get the balance between communicating the results of what we found and confusing people about what we’ve done. If we are too ‘techy’ we don’t get anywhere—if we are too bland we don’t say anything.”
But what should we be hearing? The original paper’s discussion began, “Our findings indicate that high levels of methylation in the ATM DMR [differentially methylated region in the ataxia-telangiectasia gene (ATM)] might be a biomarker of breast cancer risk.” However, interventions were not tested in women epigenetically defined as at high risk, and neither were the limits of certainty of using this method to detect risk nor the reliability of doing so in women at low risk. The press release issued by the Breast Cancer Campaign said that the research provided “strong evidence” that epigenetic risks were associated with breast cancer and stated that the women with the most methylation were “twice as likely” to get breast cancer.3
The Guardian reflected the uncertainties by reporting the “possibility of developing a simple blood test to help identify women most at risk.”4 The Daily Mail headlined with “Gene test that could predict breast cancer years before it strikes,” and in the text was clear that it would have to be “combined with other information such as a family history of breast cancer” and then it “could help identify women who might benefit from monitoring or pre-emptive action involving surgery or other drugs.”5 The Telegraph’s article said that a blood test “could detect breast cancer years in advance,” which was incorrect, and also said that the test could allow women at high risk to “take preventative medicines and switch to healthier lifestyles.”6
Mainstream media coverage lacked any deeper analysis of the accuracy or usefulness of risk assessments using this new genetic research. It would perhaps have been better to quote directly from the paper: “Adequately powered studies with blood samples collected before diagnosis will be critical for the success of . . . approaches to discover epigenetic biomarkers of cancer risk.” So, too, will be a fair assessment of the potential harms.
Cite this as: BMJ 2012;344:e3374
Competing interests: None declared.
Provenance and peer review: Commissioned; not externally peer reviewed.