Editorial
What We Know and What We Think We Know: An Editor’s Perspective on a Charged Debate Fadlo R. Khuri, MD, FACP
The September 15, 2014 issue of Cancer, and indeed the original article entitled “A Failure Analysis of Invasive Breast Cancer: Most Deaths From Disease Occur in Women Not Regularly Screened,” by Webb et al1 show a level of passionate dialogue rarely evidenced so openly in a high-quality journal. The author of the commentary entitled “Failure of Researchers, Reviewers, Editors, and the Media to Understand Flaws in Cancer Screening Studies: Application to an Article in Cancer,” Dr. Donald A. Berry,2 and Drs. Daniel Kopans, Matthew Webb, and Blake Cady, the authors of the “rebutting commentary” entitled “The 20-Year Effort to Reduce Access to Mammography Screening: Historical Facts Dispute a Commentary in Cancer,”3 are well known and highly accomplished figures in their field. It is not Cancer’s purpose to equate or compare the authenticity or expertise of these individuals. However, what is most intriguing is the fact that they take data and arrive at very different conclusions. One thing should be clear. None of the authors of the 2 commentaries or the accompanying editorial by Dr. Otis Brawley and Dr. Ruth O’Regan, 2 accomplished individuals on their own merits, dispute the finding that breast cancer screening, and indeed mammography, has benefits for women in the early detection of breast cancer. As Drs. Brawley and O’Regan conclude, “Although the benefits of mammography screening have almost certainly been exaggerated, this does not mean that it does not save lives or that women should not get it.”4 So why the strident debate, the hard feelings, and the disparate opinions among thought leaders on this highly charged topic? And why, one should ask, in a journal in which I published an editorial entitled “On Collegiality and Role Models,”5 exhorting academicians and practicing physicians alike to raise the bar and the rigor of academic debate, did we publish these disparate and often clashing opinions? The reason is that data are in and of themselves an evidentiary manifestation of truth, but they rarely are the whole truth. As a close friend and mentor of mine, the late Dr. Reuben Lotan, once counseled when an important experiment showed data that refuted our working hypothesis, “No matter how unexpected, your data always trump your hypothesis.” But how often are those data clear and subject only to one interpretation? In these discussions, you can see that phase 3 trials are examined and reexamined, modeling is performed with certain prior assumptions, and interpretations often end up on the opposite end of the spectrum. That is not to say that any of the individuals here are free of their opinion. Academic physicians and scientists, and indeed practicing clinicians, are deeply passionate about their field of endeavor. There are few fields that invoke more passion, opinions, or rigor than the question of screening women for the detection of an earlier, more curable stage of breast cancer. Interestingly, both camps, including Kopans et al3 and Berry,2 fault the media for taking the opposite side of this debate. It is relatively easy to discern why the media should have its own adherence to one side of this impassioned debate when physicians and scientists in leading positions in academia and in society believe so strongly about it and quote the evidence with such vigor. However, careful parsing of these 2 articles and the literature actually indicates that there may well be a common ground. Furthermore, I do not condone the opening conclusion of Kopans et al that “Berry and critics who wish to reduce access to screening are convinced that the improvements in therapy are the reasons that the age-adjusted death rate from breast cancer—which had been unchanged since 1930—began to decline in 1990, soon after the start of screening at the national level and temporally unrelated to any immediate advances in therapy.”3 In reviewing Berry’s commentary carefully, he emerges as an advocate for screening, but insists on evidence-based screening.2 The evidence and its interpretation are what is in question. This, after all, is what all of us (Berry, Brawley, Cady, Webb, O’Regan, Kopans, and many others) ultimately seek: evidence-based screening, something that the recent debate on lung cancer screening has yet again ignited.
Corresponding author: Fadlo R. Khuri, MD, FACP, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, 1365 Clifton Rd, NE, Bldg C-3094, Atlanta, GA 30322; Fax: (404) 778-1267; [email protected] Editor-in-Chief, Cancer DOI: 10.1002/cncr.29080, Received: September 17, 2014; Accepted: September 17, 2014, Published online October 23, 2014 in Wiley Online Library (wileyonlinelibrary.com)
4
Cancer
January 1, 2015
Editorial/Khuri
Stunningly, if a study that demonstrated a 20% reduction in lung cancer-specific mortality6cannot, once and for all, answer the question about the importance of screening in a higher at-risk population, what hope is there to resolve this issue in the substantially more impassioned debate on mammography? The reality is that the basis for consensus lies in the seeds of this debate. Most importantly, that chance for consensus is grounded in the one indisputable piece of data, which is reflected in the last sentence in the editorial by Brawley and O’Regan: “It means we need to use it with caution, honestly explain the limitations, and realize we need to develop a better test.”4 This is clearly something on which all can agree. Beyond the strongly enunciated disagreements and the powerfully coherent arguments (despite the highly effective and entertaining way in which each group has savaged the other’s points), there is little debate today that mammography does play a role in detecting breast cancer earlier and in reducing deaths from this disease. The age group, the frequency, and the power of that evidence are all in question, but the fact that for the majority of women it remains the best modality we have broadly available is not in dispute. That is something we do know as a fact. This brings us back to what we know and what we think we know. Webb et al are quite certain that they know that women aged 40 years and older should be screened for breast cancer.1 Berry argues quite convincingly that the data they are using are inadequate to make that recommendation.2 As Editor-in-Chief of Cancer, I am certainly not expert enough to settle this debate now or in the near future. One thing is clear and indisputable. Only adequately powered, large, randomized clinical trials will help to further address these burning questions. The truth, as we see clearly in the vigorous debate in these recently published articles, can be elusive. Although some are certain, as our dueling protagonists assert, that their view is known, fact-based, and certain, the reality is that there are major divides between what we know and what we think we know. Data are real and yet the interpretation of those data can vary, meaning that the ultimate truth itself, the goal and target of the principled academic, is
Cancer
January 1, 2015
often elusive and subject to biases, limits in methodologies, and what my close friend, the distinguished cancer statistician Dr. J. Jack Lee, once called “attempts to torture the data to make it confess to what one knows to be the real truth!” There are obstacles to getting to the “untortured truth,” such that what we think we know to be facts only occasionally approximate what we really do know. Perhaps the most significant challenge is one of the cancer research community’s volition. At a time when the National Cancer Institute’s support for clinical research has never been in greater question, the cutbacks in funding for the vital cancer cooperative group trial imperative endangers our ability to narrow that unseemly gap between knowledge and perception. The need to conduct truly definitive trials has never been more important, as evidenced by the vigor, thought, and passion behind the articles I have highlighted in this editorial. All of us in the cancer community—clinicians, academicians, patients, and survivors—need to step up and support, refine, enhance, and prioritize our vital clinical research enterprise, no matter which side of the screening debate we are on. FUNDING SUPPORT No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures.
REFERENCES 1. Webb ML, Cady B, Michaelson JS, et al. A failure analysis of invasive breast cancer: most deaths from disease occur in women not regularly screened. Cancer. 2014;120:2839-2846. 2. Berry DA. Failure of researchers, reviewers, editors, and the media to understand flaws in cancer screening studies: application to an article in Cancer. Cancer. 2014;120:2784-2791. 3. Kopans DB, Webb ML, Cady B. The 20-year effort to reduce access to mammography screening: historical facts dispute a commentary in Cancer. Cancer. 2014;120:2792-2799. 4. Brawley OW, O’Regan RM. Breast cancer screening: time for rational discourse. Cancer. 2014;120:2800-2802. 5. Khuri FR. On collegiality and role models. Cancer. 2013;119:928930. 6. National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409.
5
What We Know and What We Think We Know: An Editor’s Perspective on a Charged Debate Fadlo R. Khuri, MD, FACP
The September 15, 2014 issue of Cancer, and indeed the original article entitled “A Failure Analysis of Invasive Breast Cancer: Most Deaths From Disease Occur in Women Not Regularly Screened,” by Webb et al1 show a level of passionate dialogue rarely evidenced so openly in a high-quality journal. The author of the commentary entitled “Failure of Researchers, Reviewers, Editors, and the Media to Understand Flaws in Cancer Screening Studies: Application to an Article in Cancer,” Dr. Donald A. Berry,2 and Drs. Daniel Kopans, Matthew Webb, and Blake Cady, the authors of the “rebutting commentary” entitled “The 20-Year Effort to Reduce Access to Mammography Screening: Historical Facts Dispute a Commentary in Cancer,”3 are well known and highly accomplished figures in their field. It is not Cancer’s purpose to equate or compare the authenticity or expertise of these individuals. However, what is most intriguing is the fact that they take data and arrive at very different conclusions. One thing should be clear. None of the authors of the 2 commentaries or the accompanying editorial by Dr. Otis Brawley and Dr. Ruth O’Regan, 2 accomplished individuals on their own merits, dispute the finding that breast cancer screening, and indeed mammography, has benefits for women in the early detection of breast cancer. As Drs. Brawley and O’Regan conclude, “Although the benefits of mammography screening have almost certainly been exaggerated, this does not mean that it does not save lives or that women should not get it.”4 So why the strident debate, the hard feelings, and the disparate opinions among thought leaders on this highly charged topic? And why, one should ask, in a journal in which I published an editorial entitled “On Collegiality and Role Models,”5 exhorting academicians and practicing physicians alike to raise the bar and the rigor of academic debate, did we publish these disparate and often clashing opinions? The reason is that data are in and of themselves an evidentiary manifestation of truth, but they rarely are the whole truth. As a close friend and mentor of mine, the late Dr. Reuben Lotan, once counseled when an important experiment showed data that refuted our working hypothesis, “No matter how unexpected, your data always trump your hypothesis.” But how often are those data clear and subject only to one interpretation? In these discussions, you can see that phase 3 trials are examined and reexamined, modeling is performed with certain prior assumptions, and interpretations often end up on the opposite end of the spectrum. That is not to say that any of the individuals here are free of their opinion. Academic physicians and scientists, and indeed practicing clinicians, are deeply passionate about their field of endeavor. There are few fields that invoke more passion, opinions, or rigor than the question of screening women for the detection of an earlier, more curable stage of breast cancer. Interestingly, both camps, including Kopans et al3 and Berry,2 fault the media for taking the opposite side of this debate. It is relatively easy to discern why the media should have its own adherence to one side of this impassioned debate when physicians and scientists in leading positions in academia and in society believe so strongly about it and quote the evidence with such vigor. However, careful parsing of these 2 articles and the literature actually indicates that there may well be a common ground. Furthermore, I do not condone the opening conclusion of Kopans et al that “Berry and critics who wish to reduce access to screening are convinced that the improvements in therapy are the reasons that the age-adjusted death rate from breast cancer—which had been unchanged since 1930—began to decline in 1990, soon after the start of screening at the national level and temporally unrelated to any immediate advances in therapy.”3 In reviewing Berry’s commentary carefully, he emerges as an advocate for screening, but insists on evidence-based screening.2 The evidence and its interpretation are what is in question. This, after all, is what all of us (Berry, Brawley, Cady, Webb, O’Regan, Kopans, and many others) ultimately seek: evidence-based screening, something that the recent debate on lung cancer screening has yet again ignited.
Corresponding author: Fadlo R. Khuri, MD, FACP, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, 1365 Clifton Rd, NE, Bldg C-3094, Atlanta, GA 30322; Fax: (404) 778-1267; [email protected] Editor-in-Chief, Cancer DOI: 10.1002/cncr.29080, Received: September 17, 2014; Accepted: September 17, 2014, Published online October 23, 2014 in Wiley Online Library (wileyonlinelibrary.com)
4
Cancer
January 1, 2015
Editorial/Khuri
Stunningly, if a study that demonstrated a 20% reduction in lung cancer-specific mortality6cannot, once and for all, answer the question about the importance of screening in a higher at-risk population, what hope is there to resolve this issue in the substantially more impassioned debate on mammography? The reality is that the basis for consensus lies in the seeds of this debate. Most importantly, that chance for consensus is grounded in the one indisputable piece of data, which is reflected in the last sentence in the editorial by Brawley and O’Regan: “It means we need to use it with caution, honestly explain the limitations, and realize we need to develop a better test.”4 This is clearly something on which all can agree. Beyond the strongly enunciated disagreements and the powerfully coherent arguments (despite the highly effective and entertaining way in which each group has savaged the other’s points), there is little debate today that mammography does play a role in detecting breast cancer earlier and in reducing deaths from this disease. The age group, the frequency, and the power of that evidence are all in question, but the fact that for the majority of women it remains the best modality we have broadly available is not in dispute. That is something we do know as a fact. This brings us back to what we know and what we think we know. Webb et al are quite certain that they know that women aged 40 years and older should be screened for breast cancer.1 Berry argues quite convincingly that the data they are using are inadequate to make that recommendation.2 As Editor-in-Chief of Cancer, I am certainly not expert enough to settle this debate now or in the near future. One thing is clear and indisputable. Only adequately powered, large, randomized clinical trials will help to further address these burning questions. The truth, as we see clearly in the vigorous debate in these recently published articles, can be elusive. Although some are certain, as our dueling protagonists assert, that their view is known, fact-based, and certain, the reality is that there are major divides between what we know and what we think we know. Data are real and yet the interpretation of those data can vary, meaning that the ultimate truth itself, the goal and target of the principled academic, is
Cancer
January 1, 2015
often elusive and subject to biases, limits in methodologies, and what my close friend, the distinguished cancer statistician Dr. J. Jack Lee, once called “attempts to torture the data to make it confess to what one knows to be the real truth!” There are obstacles to getting to the “untortured truth,” such that what we think we know to be facts only occasionally approximate what we really do know. Perhaps the most significant challenge is one of the cancer research community’s volition. At a time when the National Cancer Institute’s support for clinical research has never been in greater question, the cutbacks in funding for the vital cancer cooperative group trial imperative endangers our ability to narrow that unseemly gap between knowledge and perception. The need to conduct truly definitive trials has never been more important, as evidenced by the vigor, thought, and passion behind the articles I have highlighted in this editorial. All of us in the cancer community—clinicians, academicians, patients, and survivors—need to step up and support, refine, enhance, and prioritize our vital clinical research enterprise, no matter which side of the screening debate we are on. FUNDING SUPPORT No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures.
REFERENCES 1. Webb ML, Cady B, Michaelson JS, et al. A failure analysis of invasive breast cancer: most deaths from disease occur in women not regularly screened. Cancer. 2014;120:2839-2846. 2. Berry DA. Failure of researchers, reviewers, editors, and the media to understand flaws in cancer screening studies: application to an article in Cancer. Cancer. 2014;120:2784-2791. 3. Kopans DB, Webb ML, Cady B. The 20-year effort to reduce access to mammography screening: historical facts dispute a commentary in Cancer. Cancer. 2014;120:2792-2799. 4. Brawley OW, O’Regan RM. Breast cancer screening: time for rational discourse. Cancer. 2014;120:2800-2802. 5. Khuri FR. On collegiality and role models. Cancer. 2013;119:928930. 6. National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409.
5
