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Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial

BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g366 (Published 11 February 2014) Cite this as: BMJ 2014;348:g366

Re: Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial

Dr. Daniel B. Kopans' claim of lack of proper randomization in the trial by Miller, et al., 2014 [1] in his response on 12-Feb-2014 is based on a paper from 1995 [2] which found more participants in the screening arm had invasive breast cancer at the start of the longterm study by Miller, et al., 2014 [1]. This bias, Kopans countered, would result in "more early deaths among the screened women than the control women", diminishing the value of mammography. Other researchers, however, were unable to verify the group allocation lapse in the work of Miller and collaborators, a specific criticism promulgated frequently by Kopans and others [3,4].

Moreover, Miller, et al., 2014, explained in their most recent study paper that "if" there was a bias in randomization at the start of the trial, "the bias would only impact on the results from breast cancers diagnosed during the first round of screening" [1] as these existing excess cancers would have been detected upon the initial or following screening, in a study that went through many screenings and lasted for over twenty years and, therefore, would not affect the results found in their latest follow-up study. Furthermore, Miller, et al., 2014 pointed out that even after this excess of incurable breast cancer is removed from the mortality analysis of the screened participants "the data do not support a benefit for mammography screening" [1].

Why didn't Kopans mention this crucial set of information in his vehement dismissal of the trial by Miller, et al., 2014 which he equates to a paper portraying a "suspect" analysis of results and "corrupted results"? Doesn't this omission indicate bias on Kopans' side, thus resulting in a display of "corrupted results" and a "suspect" commentary? It can hardly be explained by Kopans' failure to read the actual study of Miller and colleagues as he cites and refers to specific details from their paper.

Much of the criticism brought forward by Kopans had been addressed and refuted in earlier papers by Miller and colleagues [5,6] yet Kopans and others keep resorting to the same, or similar, misleading allegations.

In a prior paper of Kopans [7] he stated that the excess of breast cancer mortality, an outcome of the purported biased group allocation of individuals with invasive cancer upon trial commencement, was still apparent after ten years in the screened group of the longterm study lead by Dr. Anthony B. Miller. If this is the case it suggests screening with mammography fails to effectively detect incurable lethal cancers (but rather finds many non-cancers via overdiagnosis).

In his response, Kopans attributes the "extremely low" breast cancer detection percentage of 32%, reported in the latest analysis by the Miller group, to poor administration of the mammogram procedure, leading to missed cancers. Instead, Kopans claims, "at least two thirds of the cancers should be detected by mammography alone" based on a 2010 study he cites. However, another investigation, using data derived during the 1990s thus more consistent with the study time-frame of the Canadian trial, denoted a cancer detection of 29% by mammography alone [8].

Kopans describes in his critique how the low detection of breast cancer in the study by Miller, et al., 2014 is a sign of "the poor quality of the mammography" implementation of that study, pertaining to allegedly the use of "second hand" old mammographic equipment and the improper application of the procedure although the Miller team denoted that "the screening examination was properly conducted". The newer mammogram technology of today leads to a higher detection rate [9,10] but also elevates the magnitude of overdiagnosis, increasing the serious unnecessary harm to women via overtreatment. The extent of overdiagnosis from mammography was shown to be both large and significant [11-13].

Most of the mammogram studies showing a significant benefit are also older, having used old mammogram machines. Does the old technology argument only carry validity and relevance to adherents of mammography when a study doesn't find any meaningful value with screening? Some people would call that bias.

Kopans belittles an alleged previous notion of the study's [1] "principal investigator" -that is, the squeezing motion of the mammogram procedure can promote the influx and growth of cancer cells, leading to early deaths- as "nonsense" and a "completely unsupportable theory" with "no scientific basis". Yet, robust scientific data, published in prestigious medical journals, have lent meaningful support to the concept [14-16].

Kopans declared that he has no competing interests in his response comment but he is one of the principal developers of breast tomosynthesis, a digital form of mammography, and an inventor and patent holder (U.S. Patent No. 7,356,113) of a commercial digital breast tomosynthesis system [17,18]. Kopans also has not declared competing interests in other studies he co-authored promoting the value of his digital breast tomosynthesis system [19,20].

In my own personal, rather exhaustive, investigation of the value of mammography I have encountered numerous instances of omission, denial, derision, and obfuscation of genuinely relevant scientific data by the supporters of screening with mammography, shifting the "evidence" artificially in favor of the procedure. As a result, the general public and particularly women who decide to subject themselves to mammography, unfortunately, have been hampered from making an "informed choice" about this controversial test.

References:

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 Feb 11;348:g366. doi: 10.1136/bmj.g366.

2. Tarone RE, "The excess of patients with advanced breast cancer in young women screened with mammography in the Canadian National Breast Screening Study", Cancer. 1995 Feb 15;75(4):997-1003.

3. Cohen MM, Kaufert PA, MacWilliam L, Tate RB, "Using an alternative data source to examine randomization in the Canadian National Breast Screening Study", J Clin Epidemiol. 1996 Sep;49(9):1039-44.

4. Bailar JC 3rd, MacMahon B, "Randomization in the Canadian National Breast Screening Study: a review for evidence of subversion", CMAJ. 1997 Jan 15;156(2):193-9.

5. Baines CJ, "The Canadian National Breast Screening Study: a perspective on criticisms", Ann Intern Med. 1994 Feb 15;120(4):326-34.

6. Miller AB, To T, Baines CJ, Wall C, "Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years", J Natl Cancer Inst. 2000 Sep 20;92(18):1490-9.

7. Kopans DB, "Canadian National Breast Screening Study", Lancet. 1997 Sep 13;350(9080):810.

8. Sener SF, Winchester DJ, Winchester DP, Kurek R, Motykie G, Martz CH, Rabbitt S, "Spectrum of mammographically detected breast cancers", Am Surg. 1999 Aug;65(8):731-5; discussion 735-6.

9. Hambly NM, McNicholas MM, Phelan N, Hargaden GC, O'Doherty A, Flanagan FL, “Comparison of digital mammography and screen-film mammography in breast cancer screening: a review in the Irish breast screening program”, AJR Am J Roentgenol. 2009 Oct;193(4):1010-8.

10. Nederend J, Duijm LE, Louwman MW, Groenewoud JH, Donkers-van Rossum AB, Voogd AC, "Impact of transition from analog screening mammography to digital screening mammography on screening outcome in The Netherlands: a population-based study", Ann Oncol. 2012 Dec;23(12):3098-103. doi: 10.1093/annonc/mds146. Epub 2012 Jun 27.

11. Jørgensen KJ, Zahl PH, Gøtzsche PC, “Overdiagnosis in organised mammography screening in Denmark. A comparative study”, BMC Womens Health. 2009 Dec 22;9:36

12. Gøtzsche PC, Nielsen M, “Screening for breast cancer with mammography.”, Cochrane Database Syst Rev. 2011 Jan 19;(1):CD001877.

13. Bleyer A, Welch HG, "Effect of three decades of screening mammography on breast-cancer incidence", N Engl J Med. 2012 Nov 22;367(21):1998-2005.

14. van Netten JP, Mogentale T, Smith MJ, Fletcher C, Coy P, “Physical trauma and breast cancer”, Lancet. 1994 Apr 16;343(8903):978-9.

15. van Netten JP, Cann SA, Glover DW, "Mammographic compression: a force to be reckoned with", Br J Cancer. 1999 Dec;81(8):1426.

16. Abramovitch R, Marikovsky M, Meir G, Neeman M, "Stimulation of tumour growth by wound-derived growth factors", Br J Cancer. 1999 Mar;79(9-10):1392-8.

17. Chan HP, Wei J, Sahiner B, Rafferty EA, Wu T, Roubidoux MA, Moore RH, Kopans DB, Hadjiiski LM, Helvie MA, "Computer-aided detection system for breast masses on digital tomosynthesis mammograms: preliminary experience", Radiology. 2005 Dec;237(3):1075-80. Epub 2005 Oct 19.

18. Acciavatti RJ, Maidment AD, "Oblique reconstructions in tomosynthesis. II. Super-resolution", Med Phys. 2013 Nov;40(11):111912. doi: 10.1118/1.4819942.

19. Chan HP, Wei J, Zhang Y, Helvie MA, Moore RH, Sahiner B, Hadjiiski L, Kopans DB, "Computer-aided detection of masses in digital tomosynthesis mammography: comparison of three approaches", Med Phys. 2008 Sep;35(9):4087-95.

20. Chan HP, Wei J, Sahiner B, Rafferty EA, Wu T, Roubidoux MA, Moore RH, Kopans DB, Hadjiiski LM, Helvie MA, "Computer-aided detection system for breast masses on digital tomosynthesis mammograms: preliminary experience", Radiology. 2005 Dec;237(3):1075-80. Epub 2005 Oct 19.

Competing interests: Author of the (e)book "The Mammogram Myth"
14 February 2014
Rolf Hefti
Independent Mammogram Investigator
n/a
Los Angeles, USA
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