The Downfall of Mammography?

PET/CT study of breast cancer; injected dose: 380 MBq, tracer=F18, acquired 75 minutes after injection, body weight and size unknown, SUV max=35,9 kBq/ml, lesion size about 8cm³, CT window: 500/50, fusion image minimum threshold:10 kBq/ml; upper left image: MIP PET, upper right: axial PET, lower left: axial CT, lower right: fused image

Mammography’s reputation as gold standard in breast cancer screening took another hit this past month.  As the New York Times reported last week, research studies demonstrate that the radiation emitted by mammography can actually increase the incidence of cancer. Two nuclear technologies, breast-specific gamma imaging (B.S.G.I.) and positron emission mammography (P.E.M.), expose “patients to a risk of radiation-induced cancer that is comparable to the risk from an entire lifetime of yearly mammograms starting at 40.”

While digital mammography has an average lifetime risk of inducing 1.3 fatal breast cancers per 100,000 women aged 40 at exposure, a single B.S.G.I. exam was estimated to involve a lifetime risk 20 to 30 times greater in women aged 40, and the lifetime risk of a single P.E.M. was 23 times greater.

Moreover, mammography only increases a woman’s risk for breast cancer while B.S.G.I. and P.E.M. increase the risk of cancer in other organs, such as the intestines, kidneys, bladder, gallbladder, uterus, ovaries and colon, the study said.

That’s right, the risk of breast cancer is greater in those women that regularly receive mammograms.  At a November 30, 2009 conference, researchers reported that “for young women who have a high risk of breast cancer because of genetic mutations or family history, the radiation from yearly mammograms may make the risk even higher.”  Meta-analysis of prior research pertaining to high-risk women (0.5 - 1% of the population) with a median age of 45 found that “those women who had had mammograms or chest X-rays (which use a lower radiation dose than mammography) were more likely to have breast cancer.”

Researchers Question the Value of Mammography

The great mammogram debate began on October 21, 2009, when a Journal of the American Medical Association article stated that mammography is not as effective as anticipated:

[S]creening may be increasing the burden of low-risk cancers without significantly reducing the burden of more aggressively growing cancers and therefore not resulting in the anticipated reduction in cancer mortality… There are several reasons that may help to explain why screening has not led to a more significant reduction in deaths from these 2 diseases in the United States. First, screening increases the detection of indolent cancers. Second, screening likely misses the most aggressive cancers.

The “increasing burden of low-risk cancers” can be characterized by the high rate of false positive tests, resulting in over-treatment. As a prior HealthReformWatch post reported:

The recent analysis of all the available evidence from multiple studies published in the British Medical Journal shows that if 2,000 women are screened with mammograms regularly for ten years, only one single woman’s life will be prolonged, but 500 will have at least one false positive and ten will be diagnosed with a “cancer” that would never have become a real disease if it had been left alone.

The New York Times reports that since the mammograms became widely used in the 1980s, the diagnosis of ductal carcinoma in situ (D.C.I.S.), what many believe to be a breast cancer precursor, has increased significantly with more to more than 50,000 women in the U.S. each year.  However, the diagnosis of these borderline breast legions has raised concerns that 17 percent of diagnoses are false positives.

Researchers at Dartmouth College succinctly summed up the deficits of mammography.  In addition to the discomfort of x-ray mammography:

• The rate of false negatives from x-ray mammography range from 4% to 34%
• X-ray mammography is less sensitive in women with dense breast tissue (a common among trait among young women who are at high-risk for developing the most aggressive breast cancers)
• Seventy-five percent of biopsied lesions resulting from suspicious mammogram findings turn out to be benign (a false-positive)

It would be surprising if the Food and Drug Administration (FDA) approved an imaging modality with such poor results today.  However, the FDA never approved x-ray mammography for the diagnosis of breast cancer; it was grandfathered by the Medical Device Amendments of 1976 because it was already in clinical use.  The mammogram does not detect cancer directly, but is a measurement of tissue abnormalities such as microcalcifications, architectural distortions, masses, and asymmetrical densities.

The only mammography device to pass the pre-market approval (PMA) process is the T-Scan 2000 ED by Mirabel Medical Systems, a form of impedance imaging.  Research into impedance imaging has received attention because it does not emit radiation, can more accurately image dense breast tissue, and can differentiate between tissue types without biopsy.  Despite producing greater sensitivity in clinical trials than x-ray mammography or ultrasound, it has not become a primary imaging method.

So When Should Mammography Be Used?

The rumblings of debate turned into a roar when the U.S. Preventive Services Task Force (USPSTF) changed its breast cancer screening recommendations.  The Task Force listed many of the foregoing problems, including false positives, overdiagnosis, and radiation exposure, in support of its decision.  Despite the evidence that more effective screening measures are needed, the response in support of x-ray mammography was overwhelming.  As HealthReformWatch reported:

A number of professional and advocacy groups have responded to the Task Force’s November 16 recommendation.   The ACS continues to recommend annual screening using mammography and clinical breast examination for all women beginning at age 40.  The American College of Radiology issued a frankly titled statement, “USPSTF Mammography Recommendations Will Result in Countless Unnecessary Breast Cancer Deaths Each Year” and labeled the recommendations “cost cutting.”  And the American Congress of Obstetricians and Gynecologists continues to recommend a screening mammography every 1-2 years for women aged 40-49 years and every year for women 50 and over, as well as to recommend BSE.

The editors of Annals of Internal Medicine, which published the Task Force recommendations, responded in an editorial titled, When Evidence Collides With Anecdote, Politics, and Emotion: Breast Cancer Screening.  ”Although prevention is vital to public health, none of the previous guidelines grabbed the public’s attention as much as the Task Force’s recommendation against “routine screening mammography in women aged 40 to 49 years.”  Results of an Annals‘ website survey suggested that clinicians are more likely than the general public to be influenced by the Task Force recommendations.  In response, the editors took a position in support of the new recommendations:

Unfortunately, only a fraction of abnormalities initially detected on mammography and subsequently treated truly represents a life saved rather than unnecessary or premature treatment. Sadly, it is also true that many women who have cancer detected by screening die of the disease despite early detection and treatment… Breast cancer prematurely claims the lives of many, but it is wrong to mislead women about the effectiveness of current screening methods. Women deserve to make decisions about screening for breast cancer armed with the best available information about potential benefits and harms.

One survey respondent wrote, “This Task Force has performed a vital service for years. It brings a welcome dose of science to the politics of screening.” The editors heartily agree… Because the USPSTF issued recommendations that were politically unpopular among some constituents, there have been calls to curtail this independent body’s work. If the USPSTF sinks in turbulent waters whipped up by emotion, anecdotes, and politics, Americans should mourn its loss.

Politics and Science in the Breast Cancer Screening Debate

But what role do politics actually play in breast cancer screening?  According to Dr. Barron Lerner of Columbia University College of Physicians & Surgeons, a big one. In an interview with Kaiser Health News, he recounted:

In the late 1990s, Congress passed a bill that mandated that women who had a mastectomy would have their reconstructive surgery paid for. If you think about this, this really doesn’t happen in most areas except for breast cancer, where Congress would act, and say, “This is something we’re forcing insurance companies to do.” But it speaks to the powerful nature of the breast-cancer lobby.

One other time a report came out criticizing mammograms… the House voted 430 to nothing [ed. note: it was 424-0] — to rebuke that scientific report. So, politics is always intruding into the world of breast cancer….

In the early 1990s, there was some suggestion that if you did something called a bone marrow transplant, or stem cell transplant — which was a very aggressive treatment for metastatic breast cancer — that women live longer… The power of that lobby was so strong that insurance companies began to pay for the procedure, even though it was still experimental and its value hadn’t been proven….

It turns out that when the randomized studies came through and we got good data — at the end of the 1990s — that treatment was, in fact, no better than standard chemotherapy and caused more harm along the way. So it was not indicated at all. But, again, this was an example of Congress, or the government, sort of sticking its foot where it shouldn’t — trying to do the right thing, trying to insure access for all women who have a serious disease. But if you don’t look at the data and you’re acting based on your heart, or your gut instinct, you often make the wrong decision.

In supporting some breast cancer treatments, some lobby groups divert important resources away from important goals (e.g., development of an x-ray mammography alternative) and waste them on every promise of hope (e.g., extensive x-ray screening despite evidence of its negative effects).  The most recent example involves the new drug Avastin.

As the Fiscal Times reports, the FDA gave “accelerated approval” for the marketing of Avastin in 2008.  Two confirmatory trials submitted earlier this year led an FDA advisory committee decision to withdraw agency approval.  The first study showed that Avastin did not delay patient death and a second study indicated that patients on Avastin actually died more quickly than those on chemotherapy alone.  In spite of these findings, Susan B. Komen for the Cure chief Nancy G. Brinker and Sen David Vitter, R-La, have called upon the FDA to continue its approval of Avastin.  The FDA has yet to issue a decision.

New Breast Cancer Screening Recommendations Cause Controversy

Photo by yonjiet via Flickr

Rarely do medical recommendations or clinical guidelines receive such immediate and passionate attention as those released this month by the U.S. Preventive Services Task Force (USPSTF), an independent panel of doctors and scientists who make recommendations to the Department of Health & Human Services.  In a striking detour from prior recommendations by the Task Force and those of the American Cancer Society (ACS) that women over 40 receive a mammogram every one to two years, the Task Force now recommends:

• “against routine screening mammography in women aged 40 to 49 years”;
• “biennial screening mammography for women aged 50 to 74 years”;
• “against teaching breast self-examination (BSE)” (emphasis added).

In a radio interview on the new guidance, Dr. Bruce Calonge, chair of the Task Force, was asked about the USPSTF recommendation against routine screening for women in their 40’s and “the possibility that some women may die as a
result of not having routine mammograms.”  Calonge’s astonishing answer:

“what women really need to understand in that decade is that overall reduction in mortality, which is for all comers in that age group, only about 15%, because breast cancer is relatively rare in that age group, that benefit is really quite small…”

Although he claimed that cost analysis had no place in the Task Force’s recommendations, later, focusing on early detection generally, he repeated,

“I think one of the things that is important to say… that mammography’s benefit is only a 15% reduction in mortality.”

Kathleen Sebelius, HHS Secretary, has clarified that the federal policy on breast cancer screening has not changed, despite the Task Force’s recommendations.   In response to concerns that patients who seek mammograms before the age of 50 would not be covered by health insurance, Sebelius stated that she “would be very surprised if any private insurance company changed its mammography coverage decisions as a result of this action.”  Despite such assurances, if past experience is a guide insurance companies will use these criteria to determine coverage.

A number of professional and advocacy groups have responded to the Task Force’s November 16 recommendation.   The ACS continues to recommend annual screening using mammography and clinical breast examination for all women beginning at age 40.  The American College of Radiology issued a frankly titled statement, “USPSTF Mammography Recommendations Will Result in Countless Unnecessary Breast Cancer Deaths Each Year” and labeled the recommendations “cost cutting.”  And the American Congress of Obstetricians and Gynecologists continues to recommend a screening mammography every 1-2 years for women aged 40-49 years and every year for women 50 and over, as well as to recommend BSE.

So what would the task force’s mammography recommendations mean for patients?  The changes to the recommendations extend beyond the age at which they recommend beginning mammography screening.  For example, the 2002 USPSTF recommendations explained, “[t]he precise age at which the benefits from screening mammography justify the potential harms is a subjective judgment and should take into account patient preferences” (emphasis added).  The elimination of the term “preferences” and the focus on “patient context” and the “patient’s values regarding specific benefits and harms” indicates a move toward evidence-based medicine, whereby a patient’s inclinations and personality are taken less into consideration or play a less significant role in predicting outcomes.  In a November 17 New York Times article, the author asks,

Are you the sort for whom shivering in a paper gown, enduring discomfort and waiting a week for results is so unnerving that you are thrilled for a decade-long reprieve? Or are you that woman who gets an extra breast sonogram with your gynecologist even when it is not medically indicated? Do you trust scientists or prefer your own gut?

These concerns seem more like preferences than medically-supported decision-making factors.   The 2009 recommendations instruct that “the patient’s values regarding specific benefits and harms” be taken into account — but do not explain how far “patient context” be considered.  The recommendations do not apply to women with “known underlying genetic mutation or a history of chest radiation.”  Beyond these two exceptions, how will doctors and patients make individual decisions to start regular, biennial screening mammography?  The recommendations should be appreciated for confirming — to an extent — that the decision to begin regular screening mammography is individual.  The doctor and patient, in collaboration, should consider the patient’s risk tolerance, family history, and any other applicable factors.  Sebelius recommends that patients “[k]eep doing what you have been doing for years — talk to your doctor about your individual history, ask questions, and make the decision that is right for you.”  It is unclear how the Task Force’s recommendations could affect the decision to begin mammography in an educated and reasoned way.

The Task Force’s self-examination recommendation is also worrisome.  The USPSTF states that “there is moderate or high certainty that [BSE] has no net benefit or that the harms outweigh the benefits.”  However, discouraging the use of self-examination — a short, free, easy, and non-invasive process — might seem astonishing to many, particularly those who have known someone for whom a BSE has been the means by which breast cancer was first discovered.  Appreciating the concern about BSE leading to higher incidences of biopsies, additional screenings, and false-positive test results, with the increasing focus on disease prevention, this recommendation seems, at best, counter-intuitive, particularly when taking into account those who are uninsured and may not pursue other methods of breast cancer screening.