Drugs to prevent heart problems

Congratulations to the two cardiologists who went public with crucial information rarely explained to the public. Their target: Heart drugs prescribed to healthy people who are expected take them every day for the rest of their lives. Guess what? These drugs can be great at improving your blood test results but not so great at helping you live longer or delaying the symptoms of heart disease. (And isn’t that the point, after all?) Billions of dollars were spent annually on drugs that, initially, showed promise that didn’t hold up with long-term scientific scrutiny.  And too often, failure to prove any benefit does not dull the prescribing enthusiasm.

Vinay Prasad, MD, Northwestern University, Chicago, and Andrae Vandross, MD, Yale University, cite examples of widely prescribed drugs that were ultimately proven useless (Tricor),  dangerous (extended-release niacin), or their advantage is uncertain (Zetia, Vytorin).  In the current issue of Archives of Internal Medicine, the two cardiologists propose “setting the bar” higher for drugs prescribed to healthy people. This means clinical trials with a large number of healthy adults who are randomly assigned to take either the new drug or a placebo and are followed for many years. In other words, drug makers should prove their products can cut the rate of death, heart attack, stroke before the drugs are approved for healthy people.

As things stand now, drugs are usually approved after a few months of study on the basis of short-term results.  For example, a drug must be better than a placebo at lowering cholesterol, or blood pressure, etc.  It has long been assumed that this, in turn, will ultimately lower the rate of deaths from heart attack, stroke, etc.  This assumption hasn’t always panned out. This was shown in 2006, when a much-anticipated drug called torcetrapib was in the process of getting FDA approval for its ability to greatly increase the so-called good cholesterol. But the clinical trial had to be stopped because the drug also increased the number of deaths and heart problems.

Occasionally, the large clinical trial proposed by the two cardiologists is, in fact, conducted—-but the results aren’t in for a decade or two after the drug was approved.  Worse, prescriptions continue to rise for a drug found to be useless.  One widely prescribed drug called fenofibrate (some brand names: Tricor, Lipofen, Antara) was approved by the FDA in 1993 for the treatment of very high triglycerides in the blood. Tricor became a blockbuster four years after a 2005 meta-analysis cast doubt on the benefits of all drugs in this class known as fibrates. There were no improvements in overall survival, and this was confirmed in a landmark clinical trial. “Although it was prescribed for more than a decade to further improve lipid profiles [standard test for fats in the blood] for patients already prescribed a statin, we now know the error of this practice.”

Cost is no small matter, as noted in this paper. “Annual spending on statins exceeded $19 million in 2005, ezetimibe (in the form of Vytorin and Zetia) costs over $5 billion in 2007, and fenofibrate costs passed $1 billion in 2009.”

Another improvement suggested by Drs. Prasad and Vandross:  Drugs given to healthy people must be shown to lower the rate of deaths from all causes before they are approved.  Too often a drug will lower the rate of heart-related deaths but not the total rate of deaths. If the drug succeeds with the former but not the latter, this raises the possibility that the drug itself is killing some people.  The only way to rule this out is to demand that the clinical trials not only keep track of heart-related deaths but also total deaths.

If this sounds familiar, it is the same argument that has emerged over how to prove the lifesaving value of screening tests (also “prescribed” for healthy people). “While screening for breast, prostate, and colon cancer decreases cancer-specific death, none [emphasis added] have shown an overall mortality benefit in prospective trials,” wrote the two cardiologists.  Screening can lead to potentially fatal, unnecessary, aggressive cancer treatments.  click here for breast cancer screening,  here for prostate cancer screening, and here for colorectal cancer.

Whether these excellent proposals ever see the light of day remains to be seen.  After all, the current system of short-term pre-approval trials serves drug industry interests, and healthy people in early middle age are its favorite “market share.” (Unlike the sick and the elderly, healthy people have a longer lifespan ahead in which to take drugs.)  It’s a good idea to think long and hard before accepting “preventive” drug therapy if you don’t have heart disease.  Drs. Prasad and Vandross have given us the blueprint for the issues to be raised with the prescribing doctor.

Maryann Napoli, Center for Medical Consumers©

Related posts

Drug to prevent heart attacks and strokes

45 medical tests or treatments to avoid

Our medical care system has become a danger, an expensive, wasteful danger at that. So what else is new? You might ask. Now doctors themselves are recognizing the problem and going public with warnings, specifying tests and treatments to avoid under certain circumstances.  The primary care physicians led the way last year when they named the top ten “don’ts” in their field. Now nine specialty organizations have weighed in with their versions.  A momentous move, given the fact that these specialists are putting aside their own economic self-interest and warning their peers as well as the general public about the harm of overtesting and overtreatment.

Altogether 45 tests or treatments made the new list—five for each specialty. Yes, it’s about saving money; an estimated $660 billion is spent annually on unnecessary healthcare in U.S. And no, this is not about rationing; it’s about improving the quality of medical care and using it wisely.

The theme of this project, called Choosing Wisely, is this: Virtually all medical interventions entail some risks both large and small. An example of the former is the huge radiation dose delivered by CT scans; an example of the latter is the small chance of a puncture-related infection from a screening colonoscopy. And some tests that are risk-free can cause false-alarms that lead to more tests that are not. If you have nothing to gain from a test, why take even a small risk?

Here’s a “nothing to gain” example from the oncologists’ list: “Don’t perform PET, CT, and radionuclide bone scans in the staging of early prostate cancer or early breast cancer at low risk for metastasis.” Some reasons: “A lack of evidence to show these tests improve detection of metastatic disease or survival. Unnecessary imaging can lead to harm through unnecessary invasive procedures, overtreatment, unnecessary radiation exposure, and misdiagnosis.”

There’s also a recurring theme within the lists, namely, avoid imaging people without symptoms and people at low risk for the relevant disease. People in one or both of these categories run the risks but have nothing to gain in terms of improved outcomes. Examples: pre-operative chest x-rays, cardiac imaging stress testing for people without symptoms of heart disease.

Some lists warn against imaging even for people with symptoms, such as brain imaging for fainting or for uncomplicated headaches, because there’s no proof it improves outcomes. The cardiologists’ top five is all about inappropriate use of imaging with radionuclide and CT scans.

The strongest warning about reducing radiation exposure came from the American Society of Nuclear Cardiologists:  “Use methods to reduce radiation exposure in cardiac imaging, whenever possible, including not performing such tests when limited benefits are likely.” The word ‘methods’ also refers to calibrating the machinery to produce the best image with the lowest dose.

Sometimes a standard practice is just a waste of the patient’s time and money like this example from the allergists: “Don’t routinely do diagnostic testing in patients with chronic urticaria [hives]. Routine extensive testing is neither cost effective nor associated with improved clinical outcomes.”

Few treatments are addressed in this project, although one tops the gastroenterologists’ list.  It refers to the drugs like Prilosec and Nexium, which are widely prescribed for heartburn, gastroesophageal reflux disease, and gastric ulcers. The gastroenterologists’ advice: Use the lowest effective dose. (Click here for extensive information on this topic from Consumer Reports, which participates in Choosing Wisely.) The gastroenterologists also want their peers to restrain themselves on the repeat colonoscopies even for people who have had small polyps removed.

Another treatment example comes from the kidney specialists who are concerned about the overuse of a class of anti-anemia drugs.  “Don’t administer erythropoiesis-stimulating agents [Procrit, Aranesp, Epogen, and Eprex] to chronic kidney disease patients with hemoglobin levels greater than or equal to 10 g/dL without symptoms of anemia.” The kidney specialists could have taken a stronger stance with this example, given the fact that these drugs’ effectiveness is in doubt and they have killed an estimated half million people.  Click here for a Whistleblower’s Story.

Inform yourself

We consumers have a role in driving the market for unnecessary testing. Here’s the doctors’ side of the story: 30% of them admit that they order tests they know won’t help their patients but order them anyway because patients come in asking for them.  On the other hand, 80% of all medical care expenditures is driven by physicians.

Read more about Choosing Wisely, an initiative a foundation established by the American Board of Internal Medicine.  Click here for the names of specialty organizations and their respective lists.

Maryann Napoli, Center for Medical Consumers©
Related Posts
The primary care physicians’ list of 2011.
Heart screening tests
CT Scans: Lots of radation, little research

New Book: Mammography Screening—truth, lies and controversy

What happens when a popular cancer screening technology is found to be far more harmful than lifesaving? When the finding becomes clear decades after it was oversold to the public? When a lucrative industry, in terms of equipment, breast biopsies, drugs, etc., has already built around it that is now impossible to dismantle?

One might hope that science would win out. After all, mammography has the distinction of being a cancer screening test with extensive research behind it. In his new book Mammography Screening: Truth, Lies and Controversy (Radcliffe Publishing, London/New York: 2012), physician and research scientist, Peter C. Gøtzsche recounts what it was like to take a hard look at that research and find it didn’t match up with mammography’s sterling reputation.

The near-universal reaction? Shoot the messenger. Vicious attacks came from researchers, policymakers, and physicians. Too often aimed at the man himself rather than his critique. Opinions were fixed—mammography is risk-free and lifesaving. Anyone who disagrees publicly is causing deaths in women who might reconsider and stop having mammograms. The book describes the scientist’s 11-year investigation that uncovered mammography’s considerable harms, though they were “hiding” in plain sight—in the original studies that had long ago established mammography screening as a lifesaver.

Dr. Gøtzsche, director of The Nordic Cochrane Centre, Copenhagen, describes himself as someone who knew little about mammography when, in 1999, he was asked by the Danish Research Council to do an in-depth assessment of all mammography-related research. A statistician and expert in clinical trial design and analysis, Dr. Gøtzsche was the right man for the job. Denmark was considering a national screening program, but first wanted to know more. Bad signs were already showing up in Norway where such a program was underway. Screening decreased breast cancer deaths but, ominously, it hadn’t decreased the rate of deaths from all causes. Even more alarming, mammography failed to detect the most aggressive, deadly form of breast cancer.

Central to Dr. Gøtzsche’s conclusions are the nine randomized clinical trials that included a half million women altogether. The first took place in New York City, in the early 1960s; the last two trials were conducted in Canada and Sweden in the 1980s. “We were baffled by what we found,” he wrote. “We had expected them to be more convincing considering how popular mammography screening had become, despite its high cost.”

The results of these nine trials focused narrowly on mammography screening’s role in reducing breast cancer deaths. Dr. Gøtzsche may well be the first to step back and look at the big research picture, assessing the total death rate and the harm to women. His assessment for the Danish National Board of Health described the benefits as uncertain and raised the possibility that screening could cause more harm than good. It was ignored.

Dr. Gøtzsche continued mining the data from the nine trials and publishing frequently over the next decade. The first paper, co-authored with statistician Ole Olsen, appeared in 2000 in the British journal, The Lancet. But it was their second paper for The Lancet in 2001 that set off a furious international reaction. The nine mammography trials emphasize the number of breast cancer deaths among the participants, but Olsen and Gøtzsche contend that deaths from other causes must also be taken into consideration. These trials show that many more women given regular mammograms are treated for breast cancer than the unscreened women, and these treatments themselves may cause fatalities. Furthermore, overtreatment of ductal carcinoma in situ, often with mastectomy, was identified as “a considerable risk of mammography screening because most cases do not become invasive.” (Disclosure: I serve on The Nordic Cochrane Centre’s advisory board, am quoted in this book, and have reported Dr. Gøtzsche’s work ever since I first came across it in 2000.)

Reactions in the U.S. media were exceptionally virulent and prolonged. It was likely the first time that most physicians as well as the general public heard that some cancers will never cause death or symptoms. But this was not the first high-decibel mammography media controversy. In 1992, when the Canadian trial was published, it was roundly trashed because it came up with an unpopular finding: Mammography screening did not reduce breast cancer deaths, though it increased the number of cancers detected. Dr. Cornelia Baines, co-director of this trial, expected fellow scientists to take a dispassionate look at the finding to see why it differed from that of the earlier trials.  Instead, she became the target of numerous attempts to silence and discredit her.

When the mammography controversy surfaced again in the media in 2001, it was the policymakers, the radiologists, and the breast cancer specialists who came down hardest on Olsen and Gotzsche. To accept their conclusions would mean that hundreds of thousands of women worldwide have been treated for a type of breast cancer that would either regress or remain dormant. Who would “dig deep” into that possibility? Certainly not the doctors who for years have been sending their patients for mammograms. And certainly not the radiologists whose income had increased mightily—less from the screening test itself than from the money-making ancillary activities like stereotactic needle biopsies, continuing education courses, magnetic resonance imaging, and biopsy-related patents (click here for one example).

Most women don’t want to hear about mammography’s harms either. Fear of breast cancer sold them on mammography in the first place—without it, there would be no action to take. In the early 1970s when mammography screening was first introduced in the U.S., most American women were not particularly fearful of breast cancer, largely because it was seen as an old woman’s disease. But a multi-national cancer drug maker took care of that “problem” with annual breast cancer awareness campaigns featuring young breast cancer victims. The fear level is kept high for doctors, too, who are frequently reminded that “failure to diagnose breast cancer” is a leading cause of malpractice lawsuits.

Cancer charities take a well-deserved hit in this book for their refusal to admit that screening has a downside. Their misuse of statistics seems calculated to inflate the benefit of cancer screening. Consider the 30% reduction in deaths bandied about in the early years of mammography promotion. This statistic was downgraded recently to 15% by the U.S. Preventive Services Task Force. But both of these are relative risk statistics, which are typically misunderstood by doctors and consumers alike. Most relevant is the absolute effect of screening, not the relative effect, points out Gøtzsche who provides this explanation: “If 2,000 women are screened regularly for 10 years, 1 woman will avoid dying from breast cancer, and 10 healthy women who would not have been diagnosed without screening, will have breast cancer  diagnosed and be treated unnecessarily.”

At the end of last year, the Canadian Medical Association Journal invited Dr. Gøtzsche to write an editorial entitled, “Time to stop mammography screening?”  The Canandian Task Force on Preventive Health Care had just issued new guidelines,  stating that  “women who do not place a high value on a small reduction in breast cancer mortality, and who are concerned with false-positive results on mammography and overdiagnosis, may decline screening. ”  Dr. Gøtzsche describes this as “an important step in the right direction, away from the prevailing attitude that a woman who does not undergo screening is irresponsible.”

It’s hard to imagine that this could ever happen here in the U.S.

This book can serve as a guide to physicians and women who want to make their own informed decisions about mammograpy screening, who want an honest in-depth assessment of the research—one that should have given to the public before the introduction of mass screening. A similar “promote the test first, learn the harms later” story has unfolded recently about the PSA screening test for prostate cancer. You just might want to sharpen your critical skills and prepare in advance for the next cancer screening disaster.

Maryann Napoli, Center for Medical Consumers©

More about Dr. Gotzsche’s work:
Free mammography screening leaflet from the Nordic Cochrane Centre  It is also available  at The Nordic Cochrane Centre website in 13 languages.
Cut your risk of breast cancer—avoid screening mammograms. One-third of all breast cancers found on a mammogram are the forms of breast cancer that would never cause death or symptoms.
Breast cancer death rate has dropped, but not due to mammography  Improvements in breast cancer treatments are most likely cause. ‘Before and after’ studies conducted in countries that introduced mammography in the 1990s verify what was noticed in Norway in this era: Screening  does not detect the most deadly form of breast cancer; it has not reduced the occurrence of advanced cancers.
Poster for the 2002 Cochrane Colloquium  U.S. media coverage of the 2001 Lancet paper.

Breast cancer treatment decision aid

You have breast cancer and the initial surgical treatment is over. Now there is help with another decision that just about all breast cancer patients must make:  Should I go on adjuvant therapy, which can mean months of chemotherapy and/or years of hormone therapy? A terrific easy-to-use decision aid freely available on the Web has just been brought to my attention. It is set up to help both breast cancer patients and physicians make informed decisions about adjuvant therapy.

First, a reminder about the role of adjuvant therapy, which refers to postoperative treatments given to reduce the chance of a cancer recurrence. My recent post shows that adjuvant therapy is the main reason for the 2% annual drop in breast cancer deaths since the 1990s.  Click here  This drop, observed in many countries, coincides with the introduction of adjuvant drugs like tamoxifen and more recently Herceptin.

The decision aid is called PREDICT because it predicts a woman’s survival without and with adjuvant treatment.  Put another way, PREDICT shows how much (or how little) the additional treatment improves the chances of having a cancer recurrence.

Here’s how the website describes the basis for its predictions:  “Breast cancer comes in different types and several different factors affect the response to treatment. From research and studies involving many thousands of women we know that the response to treatment is affected by the size and type of the cancer at diagnosis, whether the cancer has spread to involve lymph nodes and whether there are estrogen or HER-2 receptors on the surface of the cells.”

To use this website you must be able to answer a few questions about your diagnosis such as tumor grade and estrogen receptor status. The predictions are presented in two easy-to-understand formats: a color chart and frequencies statistics. Here’s an example of the latter for an estrogen-positive, tumor grade 2 breast cancer in a 68-year-old woman:

“Five-year survival—90 out of 100 women are alive at 5 years with no adjuvant therapy after surgery.   An extra 1 out of 100 women treated are alive because of hormone therapy.

Ten-year survival—78 out of 100 women are alive at 10 years with no adjuvant therapy after surgery.
An extra 3 out of 100 women treated are alive because of hormone therapy.”

Unfortunately, this website does not address quality-of-life issues such as the rates of serious harm associated with each adjuvant treatment choice. Still, this is a great decision aid that deserves replication for other life-threatening diseases.

PREDICT has been developed by a partnership between the Breast cancer Unit at Cambridge University NHS Hospital, the University of Cambridge Department of Oncology and the NHS Eastern Cancer Registry and Information Centre, UK.

Maryann Napoli,Center for Medical Consumers(c)

Breast cancer deaths drop—but not because of mammography

Mammography screening is usually credited with the drop in breast cancer deaths recorded in many countries, including the U.S.  But a case is building for improvements in breast cancer treatment as the most likely cause. The decrease in deaths has occurred in many European countries that did not start  mammography screening until the 1990s, which happens to coincide with greater use of long-term adjuvant therapy (e.g., tamoxifen, chemotherapy) given after the initial treatment is over.  Researchers say the case for adjuvant therapy is made stronger by the fact that,  in some of these countries, the greatest decreases in breast cancer deaths were among young women (under 50), the age group that never received mammography screening.

As someone who has followed the “selling” of mammography screening to American women that started in the early 1970s, I offer some background for the new findings from Europe. Thanks to nearly 50 years of research, we know more about mammography than any other cancer screening test. Expert panels with no conflict of interest have concluded that the breast cancer mortality rate among mammography-screened women (in randomized trials) is only 16% lower than that of unscreened women. In the U.S., there was no reduction in breast cancer deaths until the early 1990s and about 2% a year thereafter.

Today, there is a greater understanding of cancer. Some abnormalities that look like cancer under the microscope do not become invasive, if left untreated. Many regress spontaneously, stay put, or grow so slowly they will never make their presence known.  At least as far back as the 1970s, pathologists knew about these non-progressive cancers that can occur in all major organs of the body.  But women weren’t hearing from them.  Instead, radiologists and surgeons dominated the promotion of mammography screening in the early years. Today, it is the radiologists who are often quoted in the media, warning us about the dangers of forgoing mammography screening while downplaying its harms.

Well, it is quite reasonable for women to forgo screening—that is, after becoming well-informed. Here are the highlights of several review articles published in the last few weeks.  See below for my sources.

• There are usually dramatic increases in the discoveries of new breast cancers after mammography screening takes off. Tomorrow’s cancers are found today is the standard explanation.  This  ignores the fact that in every major randomized trial, some of the regularly screened women—who have had many previous “all-clear” mammograms—are nonetheless diagnosed with  invasive tumors that are fatal despite prompt treatment.  Recent studies conducted in many countries, including the U.S., show that mammography screening has not reduced the occurrence of large invasive cancers.

• The aforementioned large increase in new cases of breast cancer without a large decrease in the rate of new cases of advanced cancer (over time) indicates that much of the increase is due to detection of non-progressive cancers (i.e., overdiagnosis). Here’s how the Cochrane review on mammography screening assessed the damage: “For every 2,000 women who are screened throughout 10 years, one will have her life prolonged. In addition, 10 healthy women, who would not have been diagnosed if there had not been screening, will be diagnosed as breast cancer patients and will be treated unnecessarily.”

• Women are often told that mammography-detected breast cancers require less drastic treatment.  The opposite is true. Mastectomy rates were going down in some European countries in the years prior to the introduction of mammography screening but went up afterwards. Many countries, including the U.S., show 20% more mastectomies in the screened women compared to the unscreened women. One factor is the large increase in the detection of ductal carcinoma in situ, or stage 0 breast cancer, which was rare in all countries prior to the introduction of mammography but is now a common diagnosis.  DCIS  is treated increasingly with mastectomy, though it has long been known that only about 20% to 30% of DCIS will go on to become invasive breast cancer if left undetected, according to Susan Love, MD, author of Dr. Susan Love’s Breast Book.

• Physicians at the Dartmouth Institute of Health Policy addressed a common misconception about mammography in a paper published online in Archives of Internal Medicine (see below). “The presumption often is that anyone who has had cancer detected has survived because of the test, but that’s not true,” according to co-author H. Gilbert Welch. “In fact, and I hate to have to say this, in screen-detected breast and prostate cancers, survivors are more likely to have been overdiagnosed than actually helped by the test …  It’s important to remember that of the 138,000 women found to have breast cancer each year as a result of mammography screening, 120,000 to 134,000 are not helped by the test.”

Maryann Napoli, Center for Medical Consumers©

Related post
There is aid for breast cancer patients who must decide about adjuvant therapy.  read more

Sources for above post
“Why mammography screening has not lived up to expectations from randomized trials.” Cancer Causes Control, published online November 10, 2011.  This is the source for virtually of the above.  Click here

Cochrane review that assessed the harms as well as benefit of mammography screening.  Click here   Want to know more about the Cochrane Collaboration?   Click here

“Likelihood that a woman with screen-detected breast cancer had her ‘life saved’ by that screening” Archives of Internal Medicine, published online October 24, 2011.  This is the source for the last bullet point.  click here    Better yet, Click here for an easier to read New York Times article about this study.  Added December 4, 2012:  YouTube vide0 explaining a new study that found mammograpy screening accounts for overdiagnosis and overtreatment of 1.3 million American women over the four decades since it was first introduced.

Lung screening scans for smokers

At the end of last year, the National Cancer Institute announced that it had stopped its lung screening trial earlier than planned. The reason: fewer lung cancer deaths among participants screened with CT lung scans compared with those screened with chest x-rays. This landmark trial is the first to show that screening can reduce lung cancer mortality in people with a history of heavy smoking. Because the National Lung Screening Trial (NLST) is taxpayer-funded, its results were reported directly to the public on the NCI website. But the NCI also made it clear that the harms associated with lung screening would not be known for months. The missing information came in this week’s issue of the New England Journal of Medicine.

The harm of screening lung scans is primarily, but not limited to, false alarms. That is, of course, the risk of all screening tests. Mammography, for example, has a high rate of false-alarms (false-positives), and studies show that most women accept this as the “price to pay” for what they perceive as the lifesaving benefit for mammography. But unlike a biopsy of the breast, which is, after all, an appendage, a needle biopsy of the lung is much riskier. Complications include death (rare, we are told) and collapsed lung (common for smokers and former smokers). Some NSLT participants went on to more invasive, risky procedures like thoracotomy and mediastinoscopy for abnormalities that turned out not to be cancer.

If you are a smoker or former smoker, your decision to be screened with a CT lung scan should involve weighing the benefit against the harms. The first thing to consider is whether you fit the profile of the people who participated in the NLST. They were male and female smokers and former smokers, age 55 to 74 years*, who were symptom-free at the start of the trial. All had smoked one pack a day for 30 years, or two packs a day for 15 years, or three packs a day for at least 10 years in the previous 15 years. The more than 53,000 participants were randomly assigned to have either a low-dose spiral computer tomography (CT) lung scan or a standard chest x-ray annually. The trial was stopped at 3 years and continued to followed participants for 3 ½ more years.

There were 356 lung cancer deaths among the more than 26,000 participants assigned to receive a spiral CT lung scan, compared to 443 among the 26,000 participants given chest x-rays (either way, a surprisingly low number of deaths for such high-risk people followed over a six-year period). But this benefit came at a huge cost in terms of money, health, and worry to the one in four people, whose scans indicated cancer, leading to more tests, a needle biopsy, and in some cases, an invasive procedure before a false-alarm was ultimately determined in the overwhelming majority of cases. False-alarms occurred in both groups, but scanning found far more abnormalities that looked like cancer before they were ultimately judged to be benign. The scans cost a couple of hundred dollars each; the “cascade” of tests that can follow are costly.

Though “low-dose” is part of its description, CT scans involve a radiation dose far higher than a standard chest x-ray but less than the standard CT scan click here. Whether annual spiral CT lung scanning itself causes lung cancer is yet to be determined. For screening mammography, the NCI estimate is: There are between 10 and 32 radiation-induced breast cancers for every 10,000 women exposed to accumulated doses of radiation received over the years from multiple mammographic examinations.

Although hospitals have already started targeting smokers with advertising for annual screening lung scans, the authors of the NLST, led by Christine Berg, MD, of the NCI’s Early Detection Research Group, do not think the technology is ready for prime time both for cost-effectiveness and safety reasons.  One concern—and it applies to all research projects—is the care delivered in the context of a clinical trial is likely to be far better than that received in the everyday practice of medicine. In the editorial that accompanied this study, Harold C. Sox, MD, Dartmouth Medical School, points out that the NLST took place at 33 academic medical centers, but the diagnostic testing and cancer treatment took place in the community, aka the real world. Dr. Sox is encouraged by the fact that the rate of death associated with diagnostic procedures was low because it indicates that diagnostic care in the community is good. However, where it concerns the radiologists who read the scans for the NLST participants, Dr. Sox suggests their skills were probably far higher than their counterparts practicing in the community. The NLST radiologists “had extensive training in the interpretation of low-dose CT scans and presumably a heavy low-dose CT workload.”

Dr. Sox wrote that he agreed with the authors of this study. “…policy makers should wait for more information before endorsing lung-cancer screening programs.”

*Participants in their seventies were underrepresented in this study (fewer than 3% of all). This means that less is known about the safety and effectiveness of screening people over age 70.

See this August 7, 2011 lung screening addition to TheNNT.com website. 

Maryann Napoli, Center for Medical Consumers©

Can this drug prevent breast cancer?

The new breast cancer study was so important that the New England Journal of Medicine made the results immediately accessible on its website. A drug, long prescribed to cut the chances of recurrence in women treated for breast cancer, has shown a modest benefit to healthy women who are at high risk for developing the disease. This is the latest in the pharmaceutical industry’s decades-long search for drugs to prevent breast cancer. Unfortunately, the new study lasted only three years, so it is not known whether the drug actually prevents breast cancer or merely delays its onset. Furthermore, it remains to be seen whether the drug can reduce the risk of dying from breast cancer.

The drug in question is exemestane (brand name: Aromasin), one of class of medications known as aromatase inhibitors, which have been prescribed for years as an adjuvant treatment for women with postmenopausal, estrogen-fueled breast cancer. It is taken for several years after the initial breast cancer treatment to reduce the risk of a recurrence. The new study is the first to try it out on healthy but high-risk women. More than 4,000 postmenopausal women, median age 63 years, were randomly assigned to take either exemestane or a placebo.

At the end of the study, there were 11 invasive breast cancers in the exemestane group and 32 in the placebo group. “Most tumors in these study patients were estrogen-receptor–positive,” noted the researchers. “HER2-positive tumors, which have a poor prognosis, were also reduced with exemestane.”

Interestingly, the research team published their findings in three different statistical formats: 1) The drug-treated women had a 65% reduction in their risk of developing breast cancer; 2)In absolute terms, this boils down to 1.4% of the untreated women developed breast cancer, compared with about a half of 1% in the drug-treated women; 3) And lastly, here is what is known as “number needed to treat”: one invasive breast cancer is avoided for every 94 women taking the drug daily for three years.

When it came to adverse effects, there were “no significant differences between the two groups in terms of skeletal fractures, cardiovascular events, other cancers, or treatment-related deaths,” wrote the research team led by Paul E. Goss, MD, Massachusetts General Hospital Cancer Center. The drug-treated women showed a small increase in (or return of) menopausal symptoms such as hot flashes, fatigue, sweating, insomnia, and joint pain. This study was described as funded by “Pfizer [maker of Aromasin] and others.”

Dr. Gross was quoted yesterday in The New York Times, describing exemestane as “very safe”, which could be overly optimistic given the fact that the study lasted only three years. Not to mention another fact that the purportedly rare serious side effects like blood clots and stroke associated with other aromatase inhibitors are unlikely to show up until a far larger number of women take exemestane than the 2,000 participants in this study. Still, exemestane is already being presented as a safer alternative to tamoxifen (brand name: Nolvadex), the first anti-cancer drug proven to reduce the risk of developing breast cancer in high-risk women. (Tamoxifen never caught on for this purpose, primarily because doctors were uneasy about prescribing a cancer drug to healthy women.)

No head-to-head comparison study has been done to determine whether exemestane is actually the safer drug, but tamoxifen is far more thoroughly studied—usually against a placebo. The seven-year follow-up data on healthy but high-risk women indicate that tamoxifen has not been proven to reduce breast cancer mortality. The drug’s estimated number needed to treat is “one breast cancer is avoided after 5 years for every 95 women taking tamoxifen, and this is reduced to 56 women in those taking tamoxifen for 10 years. To see the imperfect tool for determining who is at high risk for breast cancer, click here.

While doctors and high-risk women consider the safety and effectiveness of exemestane vs tamoxifen, the first comment to the NEJM website in response to this new study came from a doctor who raised the usually ignored topic of cost: “Correct me if I’m wrong. Exemestane costs about $300/month ($3600/year). In this study 2285 patients received the drug and were treated for 3 years. 21 fewer cases of cancer were diagnosed in the treated group than the placebo– a loudly touted 65% decrease in incidence. (32 cases in the placebo group and 12 cases in the treated group) The cost/cancer prevented = 3600 X 2285 X 3/ 21 = $1,175,142 expended per cancer prevented. Is this a rational, affordable strategy in a system that is struggling with excessive costs?” Paul Goff, MD, Everson, WA.

Maryann Napoli, Center for Medical Consumers©

Low-dose aspirin and cancer prevention

People who took aspirin daily for five years or longer were less likely to die of cancer. The study that spawned this good news, published recently in the British journal The Lancet, probably cheered those already taking a baby aspirin a day to prevent a heart attack or stroke. But the inevitable wet blanket was thrown on the new finding by another British journal, the BMJ. Even low-dose aspirin has adverse effects that could be large enough to cancel any lifesaving benefit.

The reduction in cancer deaths came from the eight clinical trials that had randomly assigned participants to take low-dose aspirin or a placebo. These are the landmark trials that showed low-dose aspirin can lower the risk of heart attack and stroke; the trials that led an estimated 20 million Americans to take a baby aspirin daily. The medical records of the 25,570 participants became a gold mine for a team of researchers who wanted to see whether aspirin can also reduce the risk of colorectal cancer death. Peter M. Rothwell and colleagues searched these medical records and found fewer deaths from several different cancers among the study participants taking aspirin, compared to those taking the placebo.

Interestingly, all the cancers were of the solid tumor type. The reduction in deaths from esophageal, pancreatic, brain, and lung cancer showed up within five years of the study and reductions in stomach, colorectal, and prostate cancer showed up later. (Many participants continued to take aspirin long after the study was over.)

Rothwell and colleagues added that the benefit increased the longer the participants took aspirin. No perfect low-dose was identified because the participants were taking 75 mg (baby aspirin) or more. Unfortunately, there were not enough women in these clinical trials to be sure that the results apply to them. And this could explain why there was no reduction in breast cancer deaths.

Now for the wet blanket, which is about the bleeding risks of low-dose aspirin. Years ago I interviewed a research physician who said that no prevention trial has tested an aspirin dose so low that there were fewer serious bleeding incidents than those recorded in the placebo group. For my readers’ sake, I went off to find the lowest dose trial which turned out to be one that tested 100 mg aspirin—every other day—against a placebo. Sure enough, even at that extremely low dose, there were more serious bleeding incidents in the aspirin group than the placebo group. To complicate things further, I could find no low-dose aspirin study, including the one reported here, that separates fatal bleeds from those that are serious but not fatal.

This known increase in bleeding risk is the major concern expressed in the BMJ editorial that urged caution about the newly identified reduction in cancer deaths. The editorialists, Paul Moayyedi and Janusz A Jankowski, called attention to how modest this finding truly is. I’ve paraphrased their explanation:

There were 20 fewer cancer deaths among the 12,785 study participants who were on low-dose aspirin for almost six years, compared with those not taking aspirin (the 12,785 in the placebo group). But 100 more serious bleeding incidents occurred in the low-dose aspirin group, compared to the placebo group.

In short, “It is not clear that the benefits outweigh the risks, even when factoring in the cardioprotective effects of aspirin,” wrote the editorialists.

So what do we do now? Should millions of middle-aged and older people be on low-dose aspirin, as is currently recommended for the prevention of heart attack and stroke? The editorialists suggest waiting for the findings from an ongoing large trial that is evaluating the effectiveness of aspirin in preventing all causes of mortality. An analysis of this ongoing trial’s findings will be reported next year.

For more information:
There’s far more low-dose aspirin research on the question of heart disease prevention. So far, it shows the risk of bleeding is tiny but so is the benefit. Here’s how one team of researchers put it: “Aspirin for primary prevention is safe and worthwhile at a coronary risk of 1.5% a year or more, safe but of limited value at a coronary risk of 1% a year, and unsafe at a coronary risk of 0.5% a year. … We have to remember that aspirin, like all other drugs, is a poison.” (To follow this advice, you’d have to ask the prescribing doctor for your heart disease risk.) For more from the researchers who came to this conclusion, click here and scroll way down to Primary Prevention.

Maryann Napoli, Center for Medical Consumers ©

Cancer screening tests right to the grave

When my husband and I picked up his mother after yet-another hospitalization for complications of congestive heart failure, I read her discharge orders. “Be sure to schedule a Pap test and a mammogram after you get home.” Naturally, we ignored the directive as absurd for a woman in her mid-nineties who clearly had a condition that would soon cause her death.

Apparently, this is more common than I’d ever imagined. A new study, published today in the Journal of the American Medical Association, found “a sizeable proportion” of people with terminal cancer are given screening tests for common cancers. And the testing is beyond the two recommended to my mother-in-law. Nearly 9% of the advanced cancer patients in this study were tested for new cancers.

Here’s how the study, funded by the U.S. National Cancer Institute, was done. Researchers at Memorial Sloan-Kettering Cancer Center, New York, searched the data from Medicare claims to determine the number of cancer screening tests given for new cancers to people already diagnosed with an advanced cancer. The reseachers assessed data on 87,736 people ages 65 and older who had been diagnosed with advanced lung, colorectal, pancreatic, gastroesophageal, or breast cancer between 1998 and 2005. All were followed up until death or December 2005, whichever came first. Each was matched by age, sex, and race to Medicare enrollees without cancer.

Keep in mind that screening is the testing of people without symptoms, and the tests may have been ordered without much thought as to what would be done once a new cancer is detected. Would a surgeon do a prostatectomy on a man with an incurable cancer some place else and a life expectancy of less than two years? I suspect the answer is yes. Why else would the test be ordered?

The tests most commonly given to advanced cancer patients were predicable. Mammography was number one, received by nearly 9% of the women with advanced cancer, with the Pap test running a close second at nearly 6%. As for the men, 15% got a PSA test and nearly 2% of all got a colonoscopy. As for the age-matched people without cancer in the control group, 2-3 times more of them had at least one of the cancer screening tests.

Who are the most likely to be screened right to the grave? Married people with higher socioeconomic status. And people who were screened regularly before they were diagnosed with the cancer that would eventually cause their death.

On this last point the research team led by Camelia S. Sima, M.D., hypothesized that “efforts to foster adherence to screening have led to deeply ingrained habits. Patients and their health care practitioners accustomed to obtaining screening tests at regular intervals continue to do so even when the benefits have been rendered futile in the face of competing risk from advanced cancer.”

Maybe so, but I suspect that something more than mindless aggressive testing is at play here. America has a death-denying culture. Continued testing keeps hope alive and avoids that unpleasant conversation about the end-of-life. It’s not over until your doctor stops ordering cancer tests.

Maryann Napoli, Center for Medical Consumers©

Improved treatment trumps mammography

Is there any point in writing about the latest mammography screening study? Opinions are entrenched on both sides—people who think the technology is lifesaving and people like me (a much smaller group) who follow the supporting research and see its lifesaving benefit as far outweighed by its well-documented risks. It is, however, worth mentioning a new study conducted in Norway that answers an important question that has nagged cancer researchers for years. Is the declining breast cancer death rate, seen in the U.S. and other Western countries, due to mammography screening or improvements in treatment? The findings, published yesterday in the New England Journal of Medicine, indicate that mammography accounts for only a small percentage of mortality reduction.

Norway did not start its national screening program until 1996 when women between the ages of 50 and 69 years were offered mammography every two years. In anticipation, the country set up what was described as “multidisciplinary breast cancer management teams [surgeons, pathologists, oncologists, radiologists, etc.] to provide comprehensive and integrated optimization of breast-cancer care.” Norway has a population of 6.8 million and a cancer registry that includes nearly 100% of its cancer patients.

The researchers led by Mette Kalager, MD, based their findings on registry data from over 40,000 women with breast cancer. They compared the breast cancer deaths among women diagnosed and treated in the nine-year period prior to, and the nine-period following, the introduction of mammography screening. Because the program had staggered implementation, the researchers were able to include women who lived in areas where mammography was still unavailable.

In the editorial that accompanied this study, H. Gilbert Welch, MD, Dartmouth Medical School, observed that the Norwegian researchers could separate the mortality reduction effect of mammography from other other factors that may have changed over time, such as treatment improvements and awareness campaigns that now make women react more quickly to a new breast symptom than they would have in an earlier era. Mammography’s benefit was found to be “disappointingly small,” accounting for only a 10% reduction in breast-cancer death among women between the ages of 50 and 69 years. [Note: Hiding in plain sight—in the new study’s abstract—was the fact that this small reduction is not statistically significant, i.e., the finding is due to chance. This was noted by Peter Gotzsche, MD, professor and director of the Nordic Cochrane Centre and the world’s leading authority on the research basis for mammography screening. click here]

This is not the first study to find a marginal benefit to mammography screening. Nor is Norway the first country to use cancer registry data to see what happened after mammography screening was introduced. Denmark, for example, found that the mortality rate declined 1% per year in the screening areas, but—brace yourself for the unexpected—there was a bigger decline (2%) per year in the non-screening areas and breast cancer deaths decreased even in women too young to be screened click here.

Back to the Norwegian study, Kalager and colleagues make the point that mammography screening requires a back-up of good comprehensive care available to all: “Our results support the evidence that screening mammography reduces the rate of death from breast cancer. However, the magnitude of the benefit seems modest in the high-attendance, nationwide screening program we evaluated. Most important, the apparent benefit conveyed by optimized patient care may be missed unless mammography screening is integrated into a well-functioning health care system that is available to the entire population.”

This point was driven home when the researchers looked at women over the age of 70 years who, in Norway and virtually all other countries (except the U.S.), do not undergo mammography screening. The unscreened women in this age group had an 8% reduction in breast cancer deaths which was attributed to the comprehensive-care teams.

So what do these findings have to do with American women? Hard to say. Obviously, we don’t have universal access to medical care, much less to mammography screening. Women treated at academic medical centers might be seen by multidisciplinary teams, but it’s unlikely to be the norm. The breast cancer mortality rate in the U.S. has decreased by roughly 2% a year since the 1990s. This study indicates that the rate could drop further if we too had universal access and a medical care system that offers the same high-quality care for all.

This study gives us something else to think about—Is mammography screening a good use of limited financial resources? This is a technology that causes a high rate of false-alarms, biopsies, and unnecessary treatment of healthy women with breast cancers that would never progress had they been left undetected. With such a small lifesaving benefit in return, mammography screening may have already crowded out other, more promising ways to lower the breast cancer death rate.

Maryann Napoli, Center for Medical Consumer©

For previous articles on this topic, type the word mammography in the search box on our home page.