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Friday, December 21, 2012

Muddled mammography

To whatever extent the oft-troubled waters of breast cancer screening had cleared since the last salient controversy, they have been stirred up again by a study just published in the New England Journal of Medicine. The paper, which has received widespread media attention, suggests in essence that mammography routinely finds cancers that would be better left unfound--cancers that would not progress, and do not need treatment.

The authors assert that 1.3 million women in the U.S. over the past 30 years have been diagnosed with breast cancer that would have remained latent without treatment. In 2008, the most recent year for which data are included in their analysis, such unnecessary diagnoses affected 70,000 women, or just over 30% of all breast cancers diagnosed that year.

The authors make this case by examining time trends in the frequency with which both early-stage and late-stage breast cancer is diagnosed. They argue, reasonably, that the benefit of screening is finding early-stage cancers that would progress to late-stage cancers if not detected. And so, each early-stage cancer found through screening should--they tell us--be one less late-stage cancer. Over the past several decades, that has not been the case; the rise in incidence of early-stage cancers is much larger than the fall in incidence of late-stage cancers.

On this basis, the authors conclude: The discrepancy between the two represents over-diagnosis. They go on to suggest that the decisive decline in breast cancer mortality over recent years is due entirely to better treatments, not to the early detection offered by screening.

The researchers in this case may be right, which is why their paper was published in NEJM. But there are important ways in which they may be wrong.

Some early-stage cancers may progress despite treatment. Many late-stage cancers may be treated effectively, but the treatments required may be far more onerous than treatment at earlier stages. Mortality is an important measure, but so is survivable misery.

And then there is the fact that some studies have told us mammography does, indeed, reduce mortality. Other studies, all but indistinguishable, have refuted it.

Rather than revisit the particulars of the mammography debate, which are receiving abundant attention already, my intent here is to address why cancer screening, which is quite literally looking for trouble, can at times seem to be so in the figurative sense as well. Then, I'll suggest what we can do about it, individually, and collectively.

There are two basic problems with cancer screening in general, problems that pertain as much or more to prostate cancer as to breast cancer. The first is the challenge of accurate detection, and the second is the challenge of accurate prediction. Let's deal with them in turn.

The very point of screening is to find cancers when they are tiny and subtle, not when they are large, obvious masses eroding through other body parts. The earlier a cancer is found, the harder it is to see both because it's tiny, and because it may look a whole lot like the healthy tissue around it.

The challenge of finding something tiny and subtle is met, in statistical parlance, with sensitivity. Sensitivity is the ability, in this context, for a medical test to find what's there.

But there is a problem with extreme sensitivity, and one not limited to medical testing. Imagine you drop a contact lens in a large room with a multicolored floor and dim light. As you search for it, you are apt to react with a moment of excited hope to any glint off the floor. In order not to miss your contact lens, you will be highly sensitive to any such glint.

But you will, in all probability, get excited by a whole batch of glints that are not your contact lens. These are called "false positives" in statistical parlance, and they are one form of over-diagnosis to which screening programs are subject.

But unless you have a perfect ability to detect the glint off of a contact lens without fail, and never mistake it for any other kind of glint. These false positives are the price you pay for any hope of finding that lens. In cancer screening, they are the price paid for finding the cancers that are truly there, and need to be found.

The other goal of cancer screening is to rule out disease when it's absent. In statistical terms, specificity is the tendency for a test to give a negative result when disease is truly absent.

But here, too, there is a price to pay. If in the case of your missing contact lens you never want the rush of false hope, there is a good chance you will ignore the subtle clues emitted by the lens. In order to avoid false hope, you may lose your real chance. This is called a false negative, and in cancer screening, it's a test that says there is no cancer when, in fact, there is.

The solution to this problem is improved technology. Ideally, we would devise a perfect test: one that unfailingly finds what it needs to find, and never mistakes anything else for it. But tests that produce no false positives, nor false negatives are vanishingly rare in medicine.

The next-best thing is enhanced technology that produces very high levels of specificity and sensitivity. In the case of mammograms, this would mean enhanced imaging, or computer-aided interpretation of the images. It might mean alternatives to mammography, such as ultrasound, or thermography. Or combinations.

A combination of screening tests is used routinely for HIV, for example. The initial screening test, called an ELISA, is very sensitive, but not very specific. That makes it good for ruling out HIV, but not reliable for ruling it in. A highly-sensitive test will very reliably be positive when disease is present, and thus a negative result on a highly-sensitive test tells you with a high level of confidence that disease is, in fact, absent. A negative ELISA is taken to mean no HIV.

But since the ELISA is so sensitive, it can be positive even when HIV is not there. So a second test, a Western Blot, is used. This test is highly specific. Since a specific test will reliably be negative when disease is absent, a positive result on a highly-specific test tells you with a high level of confidence that disease is, in fact, present. A positive Western Blot means, alas, that HIV has been found.

Enhanced technologies for breast cancer screening are in various stages of development and testing. So are combinations of tests. One of the limiting factors, of course, is cost. Better technology usually costs more. Our society must confront the challenge of best-possible breast cancer screening at a price the system is able and willing to bear.

The second challenge is prediction. The new study doesn't really highlight the flaws in mammography. Rather, it suggests we don't know what to do with the information the test gives us. Some early-stage breast cancers, in particular, ductal carcinomas in situ, are destined never to progress. This is true of many prostate cancers as well, and the reason for formal recommendations against routine prostate cancer screening.

We don't want just to find cancer early; we want to change health outcomes for the better by finding cancer early. That doesn't happen when cancer is found that would never have progressed if left alone.

The solution here is deeper knowledge at the cellular level. Gene variants can help anticipate cancer behavior. A combination of reliable detection through better technology, and then better information from biopsy specimens, should lead us in the direction of treatment when it's needed, away from it when it isn't.

In the interim, I think we all need to suppress our passions so we can work through the challenge of decisions that are far from easy. Advocates of cancer screening tend, on the basis of emotion rather than evidence, to dismiss studies that argue against overwhelming benefits of screening. Therapeutic nihilists who think screening is just a money-making gimmick tend to have equally passionate reactions in the opposite direction. Browse cyberspace and you will readily find a mother lode of both.

But these really are tough calls. Any given individual woman is more likely to have a false positive mammogram at some point, than to have her life saved by one. Ditto for prostate cancer screening in men. But some women will indeed have their lives saved by mammography, just as some men will have their lives saved by PSA testing. We just have trouble knowing who's who.

And therein lies the trouble with the kind of looking for trouble cancer screening requires. You may be the one helped; you may be the one harmed.

I favor access to and reimbursement for mammography until or unless we have truly decisive evidence of more harm from it than benefit. I do not think that will happen. Even though the argument for prostate cancer screening is weaker, I favor access to and reimbursement for that as well. Individual choice should be informed by personal preference, family history, and customized guidance from a health-care professional you trust.

Mammography specifically, and cancer screening in general, is often something of a muddle. It doesn't help us to refute this, or simply rant in favor of our preconceived notions. We should acknowledge the trade-offs, work toward better screening methods, and in the interim, muddle through.

David L. Katz, MD, FACP, MPH, FACPM, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care. He is a board certified specialist in both Internal Medicine, and Preventive Medicine/Public Health, and Associate Professor (adjunct) in Public Health Practice at the Yale University School of Medicine. He is the Director and founder (1998) of Yale University's Prevention Research Center; Director and founder of the Integrative Medicine Center at Griffin Hospital (2000) in Derby, Conn.; founder and president of the non-profit Turn the Tide Foundation; and formerly the Director of Medical Studies in Public Health at the Yale School of Medicine for eight years. This post originally appeared on his blog at The Huffington Post.

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Members of the American College of Physicians contribute posts from their own sites to ACP Internistand ACP Hospitalist. Contributors include:

Albert Fuchs, MD
Albert Fuchs, MD, FACP, graduated from the University of California, Los Angeles School of Medicine, where he also did his internal medicine training. Certified by the American Board of Internal Medicine, Dr. Fuchs spent three years as a full-time faculty member at UCLA School of Medicine before opening his private practice in Beverly Hills in 2000.

And Thus, It Begins
Amanda Xi, ACP Medical Student Member, is a first-year medical student at the OUWB School of Medicine, charter class of 2015, in Rochester, Mich., from which she which chronicles her journey through medical training from day 1 of medical school.

Ira S. Nash, MD, FACP, is the senior vice president and executive director of the North Shore-LIJ Medical Group, and a professor of Cardiology and Population Health at Hofstra North Shore-LIJ School of Medicine. He is Board Certified in Internal Medicine and Cardiovascular Diseases and was in the private practice of cardiology before joining the full-time faculty of Massachusetts General Hospital.

Zackary Berger
Zackary Berger, MD, ACP Member, is a primary care doctor and general internist in the Division of General Internal Medicine at Johns Hopkins. His research interests include doctor-patient communication, bioethics, and systematic reviews.

Controversies in Hospital Infection Prevention
Run by three ACP Fellows, this blog ponders vexing issues in infection prevention and control, inside and outside the hospital. Daniel J Diekema, MD, FACP, practices infectious diseases, clinical microbiology, and hospital epidemiology in Iowa City, Iowa, splitting time between seeing patients with infectious diseases, diagnosing infections in the microbiology laboratory, and trying to prevent infections in the hospital. Michael B. Edmond, MD, FACP, is a hospital epidemiologist in Iowa City, IA, with a focus on understanding why infections occur in the hospital and ways to prevent these infections, and sees patients in the inpatient and outpatient settings. Eli N. Perencevich, MD, ACP Member, is an infectious disease physician and epidemiologist in Iowa City, Iowa, who studies methods to halt the spread of resistant bacteria in our hospitals (including novel ways to get everyone to wash their hands).

db's Medical Rants
Robert M. Centor, MD, FACP, contributes short essays contemplating medicine and the health care system.

Suneel Dhand, MD, ACP Member
Suneel Dhand, MD, ACP Member, is a practicing physician in Massachusetts. He has published numerous articles in clinical medicine, covering a wide range of specialty areas including; pulmonology, cardiology, endocrinology, hematology, and infectious disease. He has also authored chapters in the prestigious "5-Minute Clinical Consult" medical textbook. His other clinical interests include quality improvement, hospital safety, hospital utilization, and the use of technology in health care.

Juliet K. Mavromatis, MD, FACP, provides a conversation about health topics for patients and health professionals.

Dr. Mintz' Blog
Matthew Mintz, MD, FACP, has practiced internal medicine for more than a decade and is an Associate Professor of Medicine at an academic medical center on the East Coast. His time is split between teaching medical students and residents, and caring for patients.

Everything Health
Toni Brayer, MD, FACP, blogs about the rapid changes in science, medicine, health and healing in the 21st century.

Vineet Arora, MD, FACP, is Associate Program Director for the Internal Medicine Residency and Assistant Dean of Scholarship & Discovery at the Pritzker School of Medicine for the University of Chicago. Her education and research focus is on resident duty hours, patient handoffs, medical professionalism, and quality of hospital care. She is also an academic hospitalist.

Glass Hospital
John H. Schumann, MD, FACP, provides transparency on the workings of medical practice and the complexities of hospital care, illuminates the emotional and cognitive aspects of caregiving and decision-making from the perspective of an active primary care physician, and offers behind-the-scenes portraits of hospital sanctums and the people who inhabit them.

Gut Check
Ryan Madanick, MD, ACP Member, is a gastroenterologist at the University of North Carolina School of Medicine, and the Program Director for the GI & Hepatology Fellowship Program. He specializes in diseases of the esophagus, with a strong interest in the diagnosis and treatment of patients who have difficult-to-manage esophageal problems such as refractory GERD, heartburn, and chest pain.

I'm dok
Mike Aref, MD, PhD, FACP, is an academic hospitalist with an interest in basic and clinical science and education, with interests in noninvasive monitoring and diagnostic testing using novel bedside imaging modalities, diagnostic reasoning, medical informatics, new medical education modalities, pre-code/code management, palliative care, patient-physician communication, quality improvement, and quantitative biomedical imaging.

Informatics Professor
William Hersh, MD, FACP, Professor and Chair, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, posts his thoughts on various topics related to biomedical and health informatics.

David Katz, MD
David L. Katz, MD, MPH, FACP, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care.

Just Oncology
Richard Just, MD, ACP Member, has 36 years in clinical practice of hematology and medical oncology. His blog is a joint publication with Gregg Masters, MPH.

Kevin Pho, MD, ACP Member, offers one of the Web's definitive sites for influential health commentary.

MD Whistleblower
Michael Kirsch, MD, FACP, addresses the joys and challenges of medical practice, including controversies in the doctor-patient relationship, medical ethics and measuring medical quality. When he's not writing, he's performing colonoscopies.

Medical Lessons
Elaine Schattner, MD, FACP, shares her ideas on education, ethics in medicine, health care news and culture. Her views on medicine are informed by her past experiences in caring for patients, as a researcher in cancer immunology, and as a patient who's had breast cancer.

Mired in MedEd
Alexander M. Djuricich, MD, FACP, is the Associate Dean for Continuing Medical Education (CME), and a Program Director in Medicine-Pediatrics at the Indiana University School of Medicine in Indianapolis, where he blogs about medical education.

More Musings
Rob Lamberts, MD, ACP Member, a med-peds and general practice internist, returns with "volume 2" of his personal musings about medicine, life, armadillos and Sasquatch at More Musings (of a Distractible Kind).

David M. Sack, MD, FACP, practices general gastroenterology at a small community hospital in Connecticut. His blog is a series of musings on medicine, medical care, the health care system and medical ethics, in no particular order.

Reflections of a Grady Doctor
Kimberly Manning, MD, FACP, reflects on the personal side of being a doctor in a community hospital in Atlanta.

The Blog of Paul Sufka
Paul Sufka, MD, ACP Member, is a board certified rheumatologist in St. Paul, Minn. He was a chief resident in internal medicine with the University of Minnesota and then completed his fellowship training in rheumatology in June 2011 at the University of Minnesota Department of Rheumatology. His interests include the use of technology in medicine.

Technology in (Medical) Education
Neil Mehta, MBBS, MS, FACP, is interested in use of technology in education, social media and networking, practice management and evidence-based medicine tools, personal information and knowledge management.

Peter A. Lipson, MD
Peter A. Lipson, MD, ACP Member, is a practicing internist and teaching physician in Southeast Michigan. The blog, which has been around in various forms since 2007, offers musings on the intersection of science, medicine, and culture.

Why is American Health Care So Expensive?
Janice Boughton, MD, FACP, practiced internal medicine for 20 years before adopting a career in hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling.

World's Best Site
Daniel Ginsberg, MD, FACP, is an internal medicine physician who has avidly applied computers to medicine since 1986, when he first wrote medically oriented computer programs. He is in practice in Tacoma, Washington.

Other blogs of note:

American Journal of Medicine
Also known as the Green Journal, the American Journal of Medicine publishes original clinical articles of interest to physicians in internal medicine and its subspecialities, both in academia and community-based practice.

Clinical Correlations
A collaborative medical blog started by Neil Shapiro, MD, ACP Member, associate program director at New York University Medical Center's internal medicine residency program. Faculty, residents and students contribute case studies, mystery quizzes, news, commentary and more.

Interact MD
Michael Benjamin, MD, ACP member, doesn't accept industry money so he can create an independent, clinician-reviewed space on the Internet for physicians to report and comment on the medical news of the day.

PLoS Blog
The Public Library of Science's open access materials include a blog.

White Coat Rants
One of the most popular anonymous blogs written by an emergency room physician.

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