Menopause Live (03 May, 2010) from IMS

This issue is open to all members for discussion. Anyone who wishes to make a short comment may do so, either by leaving a comment in the Feedback box at the bottom of this e-bulletin or by sending an e-mail to jwright.ims@btopenworld.com. All the comments received will be published in the June issue of Our Menopause World in a Debate section.

Previous studies have shown a 25% reduction in breast cancer mortality in Copenhagen following the introduction of mammography screening. A follow-up study was recently performed by the Nordic Cochrane Centre using an additional screening region and 5 years’ additional follow-up [1]. Jørgensen and colleagues used Poisson regression analyses, adjusted for changes in age distribution, to compare the annual percentage change in breast cancer mortality in areas where screening was used with the percentage change in areas where it was not used, during the 10 years before screening was introduced and for the 10 years after screening was in practice (starting 5 years after the introduction of screening). The study was performed in Copenhagen, where mammography screening started in 1991, and Funen county, where screening was introduced in 1993. The rest of Denmark (about 80% of the population) served as an unscreened control group. The Cause of Death Register and Statistics in Denmark for 1971–2006 was used. Amongst women who could benefit from screening (ages 55–74 years), they found a mortality decline of 1% per year in the screening areas (relative risk (RR) 0.99, 95% confidence interval (CI) 0.96–1.01) during the 10-year period when screening could have had an effect (1997–2006). In women of the same age in the non-screened areas, there was a decline of 2% in mortality per year (RR 0.98, 95% CI 0.97–0.99) in the same 10-year period. In women who were too young to benefit from screening (ages 35–55 years), breast cancer mortality during 1997–2006 declined 5% per year (RR 0.95, CI 0.92–0.98) in the screened areas and 6% per year (RR 0.94, CI 0 .92–0.95) in the non-screened areas. For the older age groups (75–84 years), there was little change in breast cancer mortality over time in both screened and non-screened areas. Trends were less clear during the 10-year period before screening was introduced, with a possible increase in mortality in women aged less than 75 years in the non-screened regions. The authors concluded that they were unable to find an effect of the Danish screening programme on breast cancer mortality. The reductions in breast cancer mortality observed in screened regions were similar to or less than those in non-screened areas and in age groups too young to benefit from screening, and are more likely to be explained by changes in risk factors and improved treatment than by screening mammography.

Comment
This paper has created a scientific storm in Europe by asserting that screening mammography, at least in this population, did not reduce breast cancer mortality. It also stimulated a lot of strong correspondence to the British Medical Journal [2], attacking the study and its authors. The main criticisms were that the populations compared were too different, did not take into account control subjects who had a private mammogram, ‘contamination’ of the data sets by pre-screening fatal breast cancers, failure to control for women already diagnosed with breast cancer prior to screening, and perhaps a difference in breast cancer treatments by region. The authors of these letters often used quite strong language such as ‘polluted data’, ‘failure of the peer review’, the analysis was ‘not credible’, and ‘more flawed research’. One critic stated, ‘This article is simply the latest in the vast amount of misinformation that has been added to the literature with regard to mammography screening’ [2]. Such language suggests to me that this paper has challenged the existing paradigm (that screening mammography lowers the death rate from breast cancer) and the respondents are reacting with anger rather than in a calm scientific manner. 

In reply, the authors point out that, if there had been an effect of screening mammography, then one would have expected to see a widening gap in the mortality rates between the screened and non-screened areas over time, as seen in the randomized, controlled trials. In contrast, the mortality rates in the two groups were parallel. Certainly, most breast cancer deaths by the end of the time of observation would be due to cancers detected during the screening period. In their letter replying to the critics, the authors suggest that much of the improved survival for breast cancer is due to improved treatments (as seen in the younger, unscreened populations) rather than early detection. 

Has screening mammography outlived its usefulness? There seems little doubt that, 20–30 years ago, it did save lives. But does screening mammography reduce breast cancer mortality now, especially since treatments are much more effective than in the past? It is difficult for the clinician to know where the truth is here. I suspect that only new, randomized, controlled trials will be able to finally answer this important question.

John Eden
Associate Professor of Reproductive Endocrinology, University of New South Wales; Director, Barbara Gross Research Unit, Royal Hospital for Women; Director, Sydney Menopause Centre, Royal Hospital for Women; Director, Women’s Health and Research Institute of Australia, Sydney, Australia

References
1. Jørgensen KJ, Zahl PH, Gøtzsche PC. Breast cancer mortality in organised mammography screening in Denmark: comparative study. BMJ 2010;340:c1241. Published March 23, 2010.
http://www.ncbi.nlm.nih.gov/pubmed/20332505
2. http://www.bmj.com/cgi/eletters/340/mar23_1/c1241