Your lecture at the recent congress on pathology focused on the issue of over-diagnosis. Tell us more.
‘Over-diagnosis in breast screening is the big issue that’s becoming a problem in the literature. The phrase suggests to the general public that the doctors have diagnosed benign issues as cancer, but in general that is not true.
‘What over-diagnosis describes is the detection of cancers by screening that would have never been otherwise recognised during the patient’s lifetime, or would never have killed the patient. Screening is great and can and does save lives, but some women will be found to have cancer that wouldn’t have been an issue in their lifetime.’
Why does it matter if we find cancer in otherwise healthy women?
‘Estimates of the rate of over-diagnosis are around one and 10 percent. Ten percent is a lot, and significantly tips the balance between benefit and harm. For those women, screening has been a disaster, because they’ve been diagnosed with cancer and had treatment, and yet they would never have known they had a tumour if they hadn’t been screened.’
What’s the root of the problem?
‘Lead-time is the time between the cancer diagnosis by screening, and when it would have become symptomatic. Current estimates suggest lead-time is two years on average. Length bias is the detection by screening of a tumour that is so slow growing that it never would have become symptomatic within a patient’s lifetime. Therefore, length bias also contributes to this over-diagnosis, as does the detection of tumours that, even if you hadn’t screened for them and detected them, could have been effectively treated anyway when they surfaced two years later.
‘You have to ask if we are doing harm to women by detecting these kinds of tumour. We are detecting things we call cancer, which are cancer by all current criteria, and yet they’re not going to kill the patient. So we’re doing the patient a disservice by saying, “You’ve got cancer, you need treatment”.’
How can those running screening programmes overcome this issue?
‘You say we need a test for aggressiveness of tumours. Studies have shown that screening-detected cancers have a less aggressive molecular signature than interval cancers. These low-grade tumours could be responsible for the over-diagnosis we see. We are in an awkward situation where we don’t know which cancers will recur and which will not, so we must treat them all. The issue is not really over-diagnosis but over-treatment.’
What is the next step?
‘Adequate funding of research and universities is needed to uncover new molecular markers of aggressiveness. It’s much more expensive to treat a patient with chemotherapy than it is to apply a test for aggressiveness of the cancer.
‘There are tests for long-term recurrence, such as EndoPredict. However, these tests are not seen to be cheap in the first instance, so aren’t always carried out. ‘We also desperately need a trial of “no treatment” for low-grade DCIS (ductal cancer in situ) cancers. The planned LORIS study by researchers at the University of Birmingham is one example. ‘Of course, it will be difficult to recruit enough people – not a lot of women would say they don’t want treatment for precancerous tumours.’
Clive Wells MD qualified from Cambridge University in 1978 having attended clinical school at St. George’s Hospital in London, and trained in histopathology at Oxford. He was appointed Consultant in Histopathology and Cytopathology at St Bartholomew’s Hospital in London in 1989 and worked there for 20 years until moving to University College Hospital in October 2009. He is now a Consultant and Honorary Senior Lecturer in Histopathology and Cytopathology. Dr Wells publishes widely on breast pathology and is Chairman of European Commission Working Group for Breast Screening Pathology (EBCN).