Five years ago, I published two blogs about research misconduct, touching on the treatment of women with breast cancer. The first highlighted a paper in the New England Journal of Medicine – suggesting that a reduction in mortality was the result of improved therapy rather than screening mammography – where the author, Gilbert Welch, was found guilty of plagiarism. The second featured a paper by Anil Potty who “invented key statistical analyses in a study of how beast cancer responds to chemotherapy,” a revelation that sent shockwaves through the cancer community, which is reliant on the integrity of scientists.
In today’s edition of Science, the editor-in-chief, Holden Thorp, published an editorial entitled “Correction is courageous” (click here to download) in which he argued that it takes courage for a scientist to acknowledge his or her mistakes and to notify a journal accordingly. He suggested that “It’s crucial that the public trusts science at a time when so many topics – artificial intelligence, climate change, and pandemics – cast shadows of uncertainty on the future.” He continued, “Evaluating policies on misconduct is essential, but the idea of a scientific ecosystem that is free of errors is an unattainable utopia.”
Thorp (seen left) argued that researchers, editors, and peer reviewers are all fallible, and what is needed is an improved approach “to strengthen the process for correcting errors in the scientific record with expedience and transparency.” He cited a recent paper by Kathleen Hall Jamieson that appeared in Proceedings of the National Academy of Sciences (click here to download) which suggested the public would be more likely to support increases in research funding if an improved approach was in place.
Thorp said, “The stigma that researchers associate with corrections and retractions, regardless of whether misconduct is acknowledged, is an obstacle to getting researchers, institutions, and journals to collaborate on better handling errors.” One solution is for journals to issue an Editorial Expression of Concern that alerts readers to a possible correction or retraction. The trouble is that some authors and institutions contest these notices.
In fact, an author of a paper published in PLOS ONE requested a correction, and the journal indicated its intention to post a notice while the correction was being considered and finalised. However, a co-author sued PLOS ONE to prevent publication of the notice, claiming it would damage her reputation. It turns out Retraction Watch has shown that corrections for an honest error do not have a negative impact on reputation, while Jamieson found support for science increases if the public believes protections are in place to reduce human bias.
In fact, the problem is far greater. The breast cancer screening “debates” have continued, in large part due to the misinformation and scientifically unsupportable claims that have passed poor peer review and been published in some of our most respected journals. Perhaps the grossest evidence of misleading the scientific community and the public is the fact that almost everyone believes the Journal of the National Cancer Institute (JNCI) is the NCI’s journal when, in fact, it was sold together with its name to Oxford University Press in 1997 and, as stated in one line at the end of a page with a long list of items
“JNCI is published monthly by Oxford University Press and is not affiliated with the United States National Cancer Institute.”
Several of the major medical journals, including JNCI, have an undeclared bias against screening, particularly for women ages 40-49 and have refused to publish data that support breast cancer screening. Perhaps the most egregious is the New England Journal of Medicine (NEJM) that has refused to publish supporting information, including from the largest screening trial – the Swedish Two County Trial – such that none of us send papers to the NEJM. Since 1990 they have published more than 24 papers that apply to breast cancer screening, and only one has provided any support for screening women ages 40-49 despite clear proof of benefit.
The most recent example is a recent publication in the NEJM by longtime opponents of screening, critical of the US Preventive Services Task Force because it, once again, supports screening women ages 40-49. Below is just a short list of the numerous pieces of misinformation in that paper:
Woloshin S, Jørgensen KJ, Hwang S, Welch HG. The New USPSTF Mammography Recommendations – A Dissenting View. N Engl J Med. 2023 Sep 21;389(12):1061-1064. doi: 10.1056/NEJMp2307229. Epub 2023 Sep 16. PMID: 37721382.
The authors ignore the fact that the previous USPSTF guidelines (biennial after age 50) were not supported by science. As with many other papers in the New England Journal of Medicine related to breast cancer screening, this recent paper should have never passed peer review:
1. There are no data (ZERO!) that have not been grouped and averaged (1), that show that any of the parameters of screening change abruptly at the age of 50 (2). It is a completely arbitrary threshold. The RCT’s of screening proved that early detection saves lives for the women who participated – ages 40-74 (PERIOD) (3).
2. The main argument against screening is now the false claim of massive “overdiagnosis” based on scientifically unsupportable papers by such authors as Dr. Welch (who left Dartmouth having been found guilty of plagiarism). The major errors in just one of his papers (4) were discussed in 3 independent reviews:
Kopans DB. Arguments Against Mammography Screening Continue to be Based on Faulty Science. The Oncologist 2014;19:107–112
Helvie MA, Chang JT, Hendrick RE, Banerjee M. Reduction in late-stage breast cancer incidence in the mammography era: Implications for overdiagnosis of invasive cancer. Cancer. 2014 Sep 1;120(17):2649-56
Etzioni R, Xia J, Hubbard R, Weiss NS, Gulati R. A reality check for overdiagnosis estimates associated with breast cancer screening. J Natl Cancer Inst. 2014 Oct 31;106(12).
Despite all of the errors in the Welch analysis, the NEJM refused to withdraw the paper.
The claim has been that, if screening was delayed until the age of 50, the fake cancers that would be “overdiagnosed”, while women were in their forties, would “disappear” by age 50. In fact, no one has ever seen a breast cancer, detected by mammography, disappear on its own (5). If you wait until the age of 50, the “fake cancers” will still be there so that “overdiagnosis” (if it even exists) will not be impacted, but the CISNET models all show that tens of thousands of women will die unnecessarily (6).
3. The paper is replete with incomplete and mis-information. They dishonestly state “the Swiss Medical Board recommended against screening mammography in all women in 2014” as if this was a Swiss national decision, failing to point out that the “Swiss Medical Board” was a self-appointed group of individuals with no governmental or National status that published in a non-peer reviewed, non-English speaking journal, and the group has since disbanded.
4. The authors ignore the fact that, in the U.S., many women have been continuously screened while in their 40’s. Inexplicably, SEER has never included the Method of Detection (MOD) (7), so there is no way of knowing how much of the decrease in breast cancer deaths that we have seen since 1990, is due to screening. Similarly, I am unable to find out how many women in their forties in Denmark, Switzerland, and the UK (cited in this paper) are being screened outside of national programs. Contrary to their assertions, in Sweden (conveniently not included), it has been shown that most of their reduction in deaths from breast cancer has been due to screening with a smaller contribution from therapy (8). The Swedish data contradict the authors’ claim ”Given the steadily decreasing mortality over the past 30 years attributable to improved treatments,….”
5. The authors imply that screening younger women should not be done because it will not reduce disparities, implying that letting women die is the better approach.
6. The authors rhetorically ask “Second, is there new evidence that the benefit of mammography is increasing?” Ignoring the fact that there is no need for “new evidence”. The USPSTF recognized years ago and reinforced in 2016 that screening saves lives for women ages 40-49.
“the USPSTF found adequate evidence that mammography screening reduces breast cancer mortality in women aged 40 to 74 years.” (9).
But, at that time, they went on to ignore the facts and their own “recognition” of the facts.
7. The authors claim “Eight randomized trials for this age group, including the most recent (the U.K. Age trial), revealed no significant effect. 2” In fact, there are numerous problems with reference 2 and its conclusions are refuted by the data. The RCT’s of screening proved a significant benefit from screening women ages 40-49 (10) as a subgroup even though the trials, initially lacked the statistical power to permit this.
8. The authors state: “In this case, it is particularly problematic that the modeled 25% relative risk reduction in breast cancer mortality with mammographic screening exceeds that observed in meta-analyses of the randomized trials”. They ignore the fact that the RCT’s can only underestimate the benefit due to “noncompliance” and “contamination”. Women who refused to accept the invitation to be screened (non-compliance) and died from breast cancer were still counted as having been screened. Women who were assigned to the control group (unscreened) but had their lives saved by screening outside the trial (contamination) are still counted as unscreened controls.
9. The authors’ arguments against modeling are the height of hypocrisy. Virtually all of Dr. Welch’s papers attacking breast cancer screening are based on his personal modeling. For example, in his 2012 paper in the NEJM (11) Dr. Welch made claims about mammography screening leading to massive “overdiagnosis” based on the SEER database, ignoring the fact that SEER does not provide any data on mammography screening. He ignored the data from the longest running Connecticut Tumor Registry (now part of SEER) that showed that the incidence of breast cancer had been increasing by 1-2% per year dating back to 1940 (12) and claimed that it had gone up by only 0.25% (his own personal model). Adding to the hypocrisy, he “remodeled” his claims in his 2016 paper (13) in which he claimed that the incidence of breast cancer had not increased at all prior to the start of screening – same data – different results and both “models” ignoring the facts!
10. “Given the steadily decreasing mortality over the past 30 years attributable to improved treatments” is a comment that is completely unsubstantiated. In fact, the study of more than 500,000 women in Sweden shows that screening and early detection is by far the largest reason that deaths from breast cancer have declined (14).
SUMMARY: The preceding comments just scratch the surface of the misinformation in this article. Unfortunately, the NEJM has a more than two-decade history of ignoring the facts and science about breast cancer screening and has continued to publish misinformation and scientifically unsupportable information (15). Dating back to 1990, the NEJM has published more than 25 papers relating to mammography screening. Only one could be construed as supportive of screening women in their forties despite numerous papers having been submitted, including from the Swedish Two County Screening Trial. Peer review has failed at the NEJM. The NEJM clearly has an undeclared bias against breast cancer screening for women ages 40-49 that it has kept hidden from its readers.
REFERENCES
1. Kopans DB. Informed decision making: age of 50 is arbitrary and has no demonstrated influence on breast cancer screening in women. AJR Am J Roentgenol. 2005 Jul;185(1):177-82. PMID: 16060005.
2. Kopans DB, Moore RH, McCarthy KA, Hall DA, Hulka C, Whitman GJ, Slanetz PJ, Halpern EF. Biasing the Interpretation of Mammography Screening Data By Age Grouping: Nothing Changes Abruptly at Age 50. The Breast Journal 1998;4:139-145.
3. Hendrick RE, Smith RA, Rutledge JH, Smart CR. Benefit of screening mammography in women ages 40-49: a new meta- analysis of randomized controlled trials. Journal of the National Cancer Institute Monograph 22: 87-92, 1997.
4.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
5. Arleo EK, Monticciolo DL, Monsees B, McGinty G, Sickles EA. Persistent untreated screening-detected breast cancer: an argument against delaying screening or increasing the interval between screenings. J Am Coll Radiol 2017; 14:863-867.
6. Hendrick RE, Helvie MA. USPSTF Guidelines on Screening Mammography Recommendations: Science Ignored. Am. J. Roentgenology 2011; 196: W112 – W116.).
7. Kopans DB, Sharpe RE Jr, Eby PR. Including the method of detection for breast cancer in the Surveillance, Epidemiology, and End Results database is long overdue. J Med Screen. 2023 Aug 25:9691413231197131. doi: 10.1177/09691413231197131. Epub ahead of print. PMID: 37624726.
8. Duffy SW, Tabár L, Yen AM, Dean PB, Smith RA, Jonsson H, Törnberg S, Chen SL, Chiu SY, Fann JC, Ku MM, Wu WY, Hsu CY, Chen YC, Svane G, Azavedo E, Grundström H, Sundén P, Leifland K, Frodis E, Ramos J, Epstein B, Åkerlund A, Sundbom A, Bordás P, Wallin H, Starck L, Björkgren A, Carlson S, Fredriksson I, Ahlgren J, Öhman D, Holmberg L, Chen TH. Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women. Cancer. 2020 Jul 1;126(13):2971-2979. doi: 10.1002/cncr.32859. Epub 2020 May 11. PMID: 32390151; PMCID: PMC7318598.
9. Siu AL; U.S. Preventive Services Task Force. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016 Feb 16;164(4):279-96. doi: 10.7326/M15-2886. Epub 2016 Jan 12. PubMed PMID: 26757170
10. Hendrick RE, Smith RA, Rutledge JH, Smart CR. Benefit of screening mammography in women ages 40-49: a new meta- analysis of randomized controlled trials. Journal of the National Cancer Institute Monograph 22: 87-92, 1997.)
11. 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
12. Anderson WF, Jatoi I, Devesa SS. Assessing the impact of screening mammography: Breast cancer incidence and mortality rates in Connecticut (1943-2002). Breast Cancer Res Treat. 2006 Oct;99(3):333-40.
13. Welch HG, Gorski DH, Albertsen PC. Trends in Metastatic Breast and Prostate Cancer. N Engl J Med. 2016 Feb 11;374(6):596.
14. Duffy SW, Tabár L, Yen AM, Dean PB, Smith RA, Jonsson H, Törnberg S, Chen SL, Chiu SY, Fann JC, Ku MM, Wu WY, Hsu CY, Chen YC, Svane G, Azavedo E, Grundström H, Sundén P, Leifland K, Frodis E, Ramos J, Epstein B, Åkerlund A, Sundbom A, Bordás P, Wallin H, Starck L, Björkgren A, Carlson S, Fredriksson I, Ahlgren J, Öhman D, Holmberg L, Chen TH. Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women. Cancer. 2020 Jul 1;126(13):2971-2979. doi: 10.1002/cncr.32859. Epub 2020 May 11. PMID: 32390151; PMCID: PMC7318598.
15. Kopans DB. More misinformation on breast cancer screening. Gland Surg. 2017 Feb;6(1):125-129.