Re: Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial
I am somewhat surprised that many of your respondents have failed to understand our study (1). Indeed, some of the comments they make are very similar to previous comments on our study, to which we responded at the time (2,3).
The most serious, and also previously answered criticisms, are those of Daniel Kopans, echoed by Eva Rubin, Paul Tartter and Jacob Levman.
Our cancer detection rate and other measures of screening quality was similar to that in the Two-County Study and superior to many others, disproving the claims that our mammography quality was poor (4). The centres in the our study did not use second hand mammography machines, many were newly purchased for the trial, all were carefully assessed by our reference physicist, who ensured the radiation dose was low and the study films of high quality. Grids were used as necessary, the study radiologists were advised by our reference radiologist and they met periodically. The technologists were properly trained, and positioning met North American standards of the time (3).
The proportion of cancers detected by mammography alone is a reflection of the high quality of the breast examinations performed. There is no comparison possible with other trials, all with the exception of the early New York HIP study did not use breast examinations. The similarity of average sizes in our two study arms only reflects the high quality of all our screening examinations.
The comments on randomization are a repetition of previously raised concerns. After Kopans accused me of scientific misconduct because of his misunderstanding of the process of randomization in the study, the National Cancer Institute of Canada arranged for randomization in the trial to be assessed by two internationally recognized epidemiologists. After full evaluation, they determined the randomization complied fully with accepted standards (5). In brief the nurses had no role in the randomization. They were trained to recognize abnormalities, not make a diagnosis, and could have no opinion on whether the woman had a cancer or not and certainly could not judge the curability of any cancers found. The numbers of women referred to the study surgeon after the first screen breast examinations was equal in the two arms. It is strange that Kopans should fail to recognize that good mammography can bring forward the diagnosis of both cancers later found to be node positive (not advanced as he stated) as well as node negative cancers.
To turn to the other comments, it is astonishing that Keith Ericson regards a hazard ratio of 0.99 as indicating a benefit of mammography screening. All his subsequent computations are based on this so-called 0.01 benefit. No one could seriously claim such a non-significant finding could be the basis of policy decisions determined by evidence. I also find it astonishing that Jacob Levman should ignore the well-recognized biases associated with survival, which as we state in the paper cannot be used to evaluate the efficacy of screening. I also find it surprising that Ruth Etzioni should largely dismiss our mortality analyses, especially that relating to the cases ascertained in the 5 year screening period, on the grounds of the apparent discrepancy between the numbers of cases detected and breast cancer mortality, The excess cases in the mammography arm are due to a combination of lead time and over-diagnosis, and therefore, the correct evaluation must be based on breast cancer mortality.
1. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for
breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ 2014;348:g366 doi: 10.1136/bmj.g366
2. Miller AB, Baines CJ, To T. Re: "Randomization in the Canadian National Breast Screening Study: a review for evidence of subversion" In response to: D.B. Kopans. CMAJ 1997;157:247-8.
3. Miller, A.B., Baines, C.J., Sickles, E.A. Canadian National Breast Screening Study. AJR 1990; 155:1133-1134.
4. Fletcher SW, Black W, Harris R, Rimer BK, Shapiro S. Screening for Breast Cancer. J Natl Cancer Inst. 1994 Apr 6;86(7):558-61.
5. Bailar JC, MacMahon B. Randomization in the Canadian National Breast Screening Study. Report of a review team appointed by the National Cancer Institute of Canada. CMAJ 1997; 156: 213-5.