Tuesday 16 July 2013

Omega 3s and cancer - confusing results

I had been planning on writing a follow up to the last article on omega 3s and chemotherapy with a piece on new research that looked at a protective effect of omega 3s on breast cancer. However, the big news of the moment is the result of a study that found that an increased risk of prostate cancer from omega 3s. So what gives? For those wanting to know whether to increase or decrease omega 3 intake, these conflicting results are just down-right confusing and a bit scary too.

Let’s deal with the prostate cancer results first. The paper in question is called ‘Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial’ and was published in the Journal of the National Cancer Institute (unfortunately not an open access publication). The abstract is available here: http://www.ncbi.nlm.nih.gov/pubmed/23843441. The authors looked at the relative percentages of different omega 3s fatty acids in blood samples from men with and without prostate cancer who had been enrolled in the Selenium and Vitamin E Cancer Prevention Trial. Men were ranked into four groups according to relative plasma omega 3 content and then the group with the lowest 25% were compared with the highest 25%. The results of this analysis showed that the men in the highest group had greater risk of prostate cancer than those in the lowest group. This was true for total omega 3 measurement as well as for individual omega 3s (e.g. DHA, DPA and EPA). On the face of it this looks like a pretty solid finding. But there are some puzzling things about this result. The first and the most obvious is that there’s no causal mechanism offered to explain a result that the authors themselves admit is puzzling and contrary to expectations. Omega 3s have many different effects in the body, for example they are strongly anti-inflammatory, but none of them known to be pro-carcinogenic or pro-tumour. Stranger still, the study found that some omega 6 fatty acids, which are known to be pro-inflammatory and often associated with being pro-cancerous, were associated with lower cancer incidence in this study.

Friday 5 July 2013

Book Review: Mammography Screening: Truth, Lies and Controversy

Keywords: Cancer, screening, medicine, public policy, science
Title: Mammography Screening: Truth, Lies and Controversy
Author: Peter C. Gotzsche
Publisher: Radcliffe Publishing Ltd
ISBN: 978-1846195853
On the face of it the case for increased breast cancer screening is clear. Cancers caught sooner are easier to excise or to treat with chemotherapy. Earlier diagnosis means a lower likelihood of metastases, which are the real killers in cancers of all kinds. So who could argue against increased screening? Unfortunately this simple picture, seductive though it is, is just too simplistic and obscures a bitter controversy that has raged across the medical literature but which barely registers in public consciousness.

Peter Gøtzsche, a Danish medical researcher, Professor of Clinical Research Design and Analysis and the director of the Nordic Cochrane Centre, is a key player in the controversy and is highly sceptical of the value of breast screening in the general population. As an expert in clinical trial design and results analysis he came to the topic with no real experience of breast oncology, chemotherapy or surgery. But it was from this position of independence that he looked at the data from the studies that had been performed on breast screening and decided, based on the evidence that he and his colleagues uncovered, that far from being an unalloyed good, there were real and significant harms being perpetrated on women taking part in breast cancer screening programs.

As Gøtzsche outlines in considerable detail in this book, his findings were not greeted with open arms by breast screening advocates, the medical establishment and numerous well-placed political and academic figures. In fact the reaction was extremely hostile and remains so to this day, many years after his initial research findings. Gøtzsche and his colleagues were attacked from all sides for straying from the 'consensus' view that screening saved lives. His results, methods and motives were all attacked and continue to be attacked, though few seem to actually dispute the core of what he has found.

And what is it that makes Gøtzsche and a few others like him dispute the simple narrative that regular screening saves women's lives? The fly in the ointment is simple - over-diagnosis. If you go looking for cancer then cancer is what you'll find. Mammography screening will find all kinds of lumps and abnormalities. Some of these will become invasive and dangerous cancers, many will not. The difficulty is that at this stage we don't know which will melt away and which will turn into killers. Given that we can't tell the difference the only thing to do is to aggressively treat all the tumours that we find. And, let's be honest, this treatment is often brutal - mastectomy, radiotherapy and chemotherapy.

In analysing the data Gøtzsche focuses on overall all-cause mortality. And his key finding is truly shocking - while some women might be saved by early diagnosis and treatment, others will die from over-diagnosis and the results of over-treatment. In their latest advice, Gøtzsche and his co-workers state that:
Screening produces patients with breast cancer from among healthy women who would never have developed symptoms of breast cancer. Treatment of these healthy women increases their risk of dying, e.g. from heart disease and cancer.
This is not a trivial finding it's a scandal that ought to have anti-cancer activists up in arms. Unfortunately many activists are so wedded to the idea of mammography being the panacea that they campaign for increases in screening rather than wanting to subject the programs in place to the critical scrutiny they deserve.

For those of us familiar with that other science war - climate-change - some of what Gøtzsche describes will be eerily similar: well-entrenched 'consensus' science subjecting sceptical voices to attack, subversion of peer review, ad hominen attacks, endless dissimulation and the knocking down of strawman arguments that sceptics do not make. The parallels between this and what goes on in 'climate science' are strong, obvious and depressing. Even more depressing is the fact that Gøtzsche himself seems to have fallen for the party line when it comes to climate change, not realising that scientists sceptical of the 'consensus' view of man made climate disaster are also subject to subverted peer review, ad hominen attack, accusations of working for commercial interests etc. Where he is accused of killing patients, anthropogenic global warming sceptics are accused of wanting to kill the planet.

Gøtzsche describes in great detail the many controversies and arguments that have ensued since going public with his results. There is a degree of repetition throughout the book, but at its core is a simple story based not on complex statistical analysis or mathematical modelling but on the raw data of what happens to women taking part in screening programs.

Where he comes back again and again to the inevitable fact of over-diagnosis, the advocates of screening focus on the fact that earlier diagnosis leads to improved outcomes for the women diagnosed. Both these things are true. But in terms of women in general, it means that large numbers of women are being turned into cancer patients unnecessarily, and that some of these will die because of the treatment they receive.

This isn't to say that screening is a bad idea per se. For women with genetic predisposition, with family histories of breast cancer or who are in other high risk groups then screening make sense. However, for the vast majority of women who are not at high risk, especially younger women, screening does not make sense and will lead to harm to a number of them. In fact Gøtzsche and the Nordic Cochrane group have published a leaflet for women, setting out the benefits and risks of screening, leaving it to women to make up their own minds based on a clear exposition of the data. It can be downloaded here: http://www.cochrane.dk

And, despite the accusations of his opponents, Gøtzsche is not alone. For example, Michael Baum, who worked for 30 years as a surgeon specialising in breast cancer, and is now professor emeritus of surgery at University College London, recently stated:
If we stopped screening today, the incidence of breast cancer would fall at a stroke by about 25 per cent.
In the end Gøtzsche's book is like the cancer version of Andrew Montford's 'The Hockey Stick Illusion'. Both books look at contentious areas of science. Both books cut through often obscure statistical arguments to get to the core of the issue. And both books describe a situation where you have tightly knit and entrenched groups of scientists with institutional backing, political support and significant funding doing their level best to lock out those who refuse to bow down to a 'consensus' that is not grounded in solid science.
Or as Gøtzsche puts it:
The screening literature has been polluted to an extraordinary degree by statistical modelling of raw data, often combined with wishful thinking and the use of favourable, but unrealistic assumptions for variables that cannot be measured. This has helped conceal inconvenient facts and has yielded results people wanted to see.
To conclude, this is essential reading for everyone interested in science, medicine and public health policy. Most of all it is essential reading for women being emotionally blackmailed into taking part in screening programs without being given all the facts.