Mammography Does Not Predict Cure

Before a breast malignancy becomes detectable by mammography it has typically been present for 8 years.

It is also worth remembering that simply because a tumor is detected by mammography does not necessarily mean that it will be cured. For example, half of the breast cancer deaths recorded in two important Swedish studies of screening were among women whose tumors had first been discovered by mammography (Duffy 1991).

Consider this: while 6 out of 1,000 50-year old women may die in the next 10 years if they do not have mammography, as many as 4 in 1,000 will still die even though they have had regular mammograms. The benefit conferred by mammography for this group of 1,000 women therefore works out to just  2 lives saved over a period of 10 years.

Mammography is also not very sensitive, particularly for younger women. In younger women the breast tissue tends to be denser than it is in postmenopausal women, making the recorded film image much more difficult to interpret. This in turn can lead to an increased likelihood of misinterpretation of the radiographic image. The same is true of a substantial proportion of postmenopausal women who are taking estrogen supplements or hormone replacement therapy. These supplements can increase breast density, making mammograms just as hard to read as those of younger women with dense breast tissue.

The advent of digital mammography, in which the traditional X-ray film is replaced by a digitized, computer-enhanced image of the breast, may make the imaging of denser breast tissue more accurate, and according to a study published in the New England Journal of Medicine in September 2005 this technique has already shown itself to be better than traditional film mammography at identifying suspicious lesions in women with radiographically dense breast tissue (Pisano 2005).

Mammography has a high false positive rate – that is, an area may be labeled suspicious, and further tests, including biopsy (the removal and examination of a sample of tissue for diagnostic purposes), may be initiated, only to find that it was a false alarm, and there is no abnormality.

Mammography, in other words, is by no means fail-safe, and over time, a very significant number of women who undergo mammography will experience at least one false positive test. One study found that if 32 million American women aged 40 to 79 years old received breast cancer screening annually for 10 years, 16 million of those women would have at least one false positive mammogram – i.e., the chance of a woman receiving a false positive test over 10 years of regular mammography is around 60 percent (Elmore1998).

If you have ever been through one or more of these "false alarms" you will know the psychological harm that they  do. Your life, and often that of your entire family, is put in abeyance, as you hold your breath awaiting the verdict of the radiologists and pathologists in your case. This agony can go on for weeks.

The chance of a false positive is compounded by the human factor: all mammograms must be 'read' (i.e., interpreted) by a radiologist, and for many reasons (not least the fear of litigation) a radiologist may err on the side of over-diagnosis, thus adding to the probability of a false positive reading. In one study, for example, almost 60 percent of responding radiologists reported that their awareness of the potential for lawsuits moderately to greatly increased the number of their recommendations for further tests, including breast biopsies (Elmore 2005).

Abnormal mammograms are far more common in the US than elsewhere in the world: approximately 11 percent of all mammograms are declared abnormal in the US versus only 2 to 5 percent in Europe. This is not because breast abnormalities are more  common in the US than elsewhere, but because there is a marked tendency to over-diagnose breast cancer in this country.

Furthermore, skill at reading mammograms varies widely depending on the particular setting in which the mammogram is performed. In the best teaching hospitals and large cancer centers radiologists may well come up to higher standards of excellence than they do in the setting of community health and screening centers. A 2002 New York Times article on this subject exposed some alarming disparities between the two settings (Moss 2002).

Mammograms can and do sometimes miss cancers entirely. A woman may have a normal mammogram at one screening but still develop a so-called ‘interval cancer' before her next examination. As we have seen in our previous newsletters, this kind of cancer tends to be the most deadly. The ‘false negative' rate – that is, the rate at which mammography gives a clean bill of health to those who in reality do have cancer,has been estimated to be somewhere between 10 and 15 percent  (Welch 2004).

The Problem of DCIS

Meanwhile, the number of cases of premalignant, non-invasive lesions such as ductal carcinoma in situ (DCIS) being diagnosed by mammography has increased by 900 percent in the US over the past 20 years. It has now reached the point where almost 20 percent of all breast cancer diagnoses involve DCIS.

Some people interpret this as a good thing, i.e., a sign that cancer is being caught in its earliest stages. Treated early or late, DCIS has a low mortality rate (around 1 percent). Precisely what percentage of these latent, precancerous lesions might eventually progress to become truly invasive is unknown, although it has been estimated that almost 50 percent of all ‘in situ' cancers will never progress and would be better left undetected and therefore untreated (Handler 2003).

Perhaps one day in the future there will be a way of distinguishing  between those women whose DCIS poses an imminent threat of  invasiveness and those whose lesions are harmless, so that treatment can be directed only towards those who truly need it. Currently, though, such a test does not exist.

Undoubtedly mammography is having the effect of labeling a substantial number of women as having breast cancer, and channeling them towards aggressive treatment, when in fact they have a pseudodisease – i.e., a benign condition that poses no threat to life.

In one large-scale Canadian study of screening mammography it was found that DCIS was diagnosed in more than double the number of women who were given mammography than in those given careful clinical breast examinations (CBE) by qualified providers (i.e., 71 such women in the mammography group compared with 29 in the breast examination group). Another large Canadian study found that 71 mammography patients were given a diagnosis of DCIS compared with only 16 in the breast examination group. Meanwhile, a careful analysis of the outcomes of both these studies concluded that mortality rates from breast cancer were unaffected by screening mammography: the women in these studies experienced no survival benefit whatsoever from mammography even after 10 years of follow up (Miller 2000).

Radiation and Other Hazards

Another important factor that is largely ignored by the medical profession and the media is the radiation danger inherent in screening mammography, particularly to younger women (i.e., women in the premenopausal age range of 40-50 years). Breast  tissue is highly sensitive to radiation: an annual exposure  to 1 cGy, or centigray (the dosage involved in taking a standard mammogram) increases the risk of cancer by 1 percent, and over a 10-year period of annual mammography screening this could augment a woman's cancer risk by 10 percent. The risk may be even greater – up to a 20 percent increased risk  - for those women who carry certain genetic mutations (Swift   1994).

In addition, annual mammography exposes the breast tissue to repeated doses of low-energy X rays. Contrary to what one might expect, low-energy X rays are actually more damaging to DNA than their high-energy counterparts, according to a study performed at Columbia University's Center for Radiological Research (Brenner 2002).

For younger women in particular, whose breasts are denser and who have a longer projected lifespan ahead of them than postmenopausal women, the additional exposure to X-rays posed by annual mammography beginning at the recommended age of 40 could pose a significantly increased risk of cancer. The Columbia University article concluded:

"There is evidence that low energy X rays as used in mammographic screening produce an increased biological risk per unit dose relative to higher energy photons. At low doses, the increased risk appears to be of a factor of 2 .For older women, the benefit is still likely to outweigh the radiation  risk. For women less than 50 years of age, however, this increase in the estimated radiation risk might indicate a somewhat later age than currently suggested, by about 5-10 years, at which to recommend commencement of routine breast screening" (Brenner 2002).

This paper is significant – and unusual - in that it both acknowledges the risks involved in repeated radiation exposure to the breast through mammography and urges a re-examination of current recommendations concerning the appropriate age to begin regular screening. Most discussions of mammography are not as frank.

Another hidden hazard in mammography is the physical compression of the breasts that is necessary to obtain a readable radiographic image. This physical compression can result in the rupture of small blood and lymphatic vessels, which, if they are in close proximity to a tumor – even a tiny tumor – may result in the release of malignant cells into the general circulation (Rosser 2000).

The Mammography Paradox

That mammography is not as effective in saving lives as its promoters have insistently claimed is bad enough, but more alarming by far is the little-publicized fact that in women aged 40-49, mammography is actually associated with an increased, rather than a decreased, risk of death- a phenomenon known to researchers as the "mammography paradox."

Yes, you read that right: mammography in younger women (ages 40-49) may actually accelerate, rather than reduce, breast cancer mortality.

This increased death rate from breast cancer in younger women who undergo screening mammography has been documented consistently in screening trials across different countries, settings and populations. It is a fact known to many researchers in the field, yet it remains largely unknown to the general public – and it certainly not a danger of which women are routinely made aware by their healthcare providers.

One critic of exclusive reliance on screening mammography is Cornelia J. Baines, MD., of the University of Toronto. Dr. Baines is hardly an outsider to the field. She is deputy director of the prestigious Canadian National Breast Screening Study, and the author of 70 PubMed-listed journal articles. She has also written an important paper that is frank in its discussion of this issue. In this paper, aptly titled "Mammography screening – Are women really giving informed consent?" Dr. Baines says: "Many women remain unaware of the extent to which efforts to achieve breast cancer control through mammography screening may be doing harm as well as good. An unacknowledged harm is that for up to 11 years after the initiation of breast cancer screening in women aged 40-49 years, screened women face a higher death rate from breast cancer than unscreened control women, although that is contrary to what one would expect" (Baines 2003).

How could this happen? How can it be that instead of saving  their lives, earlier detection might actually result in a greater likelihood of death in these women?

Cornelia J. Baines, MD, of the University of Toronto, deputy director of the prestigious Canadian National Breast Screening  Study, has written several papers that are critical of screening mammography. She writes: "An unacknowledged harm [of screening mammography, ed.] is that for up to 11 years after the initiation of breast cancer screening in women aged 40-49 years, screened women face a higher death rate from breast cancer than unscreened control women, although that is contrary  to what one would expect" (Baines 2003).

How could this happen? How can it be that instead of saving their lives, earlier detection might actually result in a greater likelihood of death in these women?

It is a phenomenon well known to researchers that the removal of the primary tumor can trigger the sudden growth of tiny clusters of cancer cells (called ‘micrometastases') that have until that point lain dormant in distant sites. Researchers have shown that the primary tumor inhibits the ability of these subsidiary distant deposits to grow, perhaps by releasing powerful biologically active substances, such as angiostatin and endostatin, which prevent tumors from stimulating the development of their own blood supply (a process known as angiogenesis).

Without the ability to generate a new and adequate blood supply, tumors, even tiny, clinically invisible tumors, cannot grow, and while the primary tumor is still in place, and still secreting these angiogenesis-suppressing substances, the micrometastases remain dormant. But once the primary tumor – the "conductor of the cancer orchestra," so to speak – has been removed, the restraints on growth are removed and the microscopic malignant deposits in distant sites suddenly acquire the power to induce their own blood supply and grow independently.

Much of the pioneering work on the role of angiogenesis in tumor growth was done by Judah Folkman, MD, of Harvard University, winner of the American Society of Clinical Oncology's (ASCO) highest honor, the Karnofsky Award (1996). Working alongside  Prof. Folkman, Dr. Michael Retsky and other researchers have studied the question of the mammography paradox and have suggested  that not only is the removal of the primary tumor the spur to proliferation of dormant metastases, but also that surgery itself, by creating a physical wound, independently triggers the release of growth factors that, in addition to assisting  healing of the surgical wound, also promote tumor growth. This effect is particularly marked in younger women with node-positive disease.

The fact that the mammography paradox is confined to younger (as opposed to older) women undergoing mammography is a reflection of the biological differences between pre- and postmenopausal women, Dr. Retsky and his colleagues suggest. In premenopausal women, the hormonal environment may encourage the estrogen-driven proliferation of breast cancer cells, putting younger women at an extra disadvantage in terms of their susceptibility to aggressive metastatic cancer growth.

For a previous newsletter on the subject of Retsky's work on the role of surgery in stimulating cancer growth, please click or go to:

http://www.cancerdecisions.com/073105.html

In a 2001 paper on the subject of the mammography paradox, published in the journal Breast Cancer Research and Treatment, Dr. Retsky and colleagues state that "Each woman should be informed of the risks and benefits [of mammography] and  decide for herself whether to undergo screening mammography. Young women are, however, not routinely warned that screening and resection may accelerate breast cancer mortality" (Retsky 2001).

This sentiment is echoed by the University of Toronto's Dr. Baines, who asks, "Shouldn't women aged 40-49 years know that, 3 years after screening starts, their chance of death  from breast cancer is more than double that for unscreened control women? Shouldn't they be informed that it will take 16 years after they start screening to reduce their chance of death from breast cancer by a mere 9 percent?"

Dr. Baines, the author of 70 PubMed-listed scientific articles, also points out that there is an almost willful silence both within and outside the medical profession on the subject of the dangers and ineffectiveness of screening mammography. Although the mammography paradox was originally identified in an article published in 1997 in the Journal of the National Cancer Institute, this important news was cited only 8 times in the ensuing 6 years – and four of these citations were by the same group of researchers (Cox 1997).

Contrast this peculiar absence of debate with the deafening clamor from all sides in favor of mammography screening – and with the mounting chorus in support of the recommendation that women should begin annual mammography at the age of 40 - the very group of women most likely to be harmed, rather than helped, by mammography.

It is often fear that drives women to seek screening mammography, a fear that is fostered, actively and tacitly, by a medical profession (and a highly profitable screening industry) that is doing little to inform women of their real risks, nor what gain, if any, they can really expect from mammography.

The risk of developing breast cancer is 11 percent (1 in 9) over a woman's lifetime. While women tend to believe that almost 40 percent of all deaths among women are due to breast cancer, in reality the actual percentage is 4 percent. In a survey of 1000 American women, 71 percent expressed the belief that screening reduces breast cancer deaths by 50 to 100 percent (Domenighetti 2003).

Meanwhile, several rigorous clinical trials have shown that mammography not only does not confer a clear survival benefit, but may in fact have the opposite effect, contributing to an increased, rather than a reduced risk of dying in premenopausal women. Despite these stark facts, raising questions about the value of mammography has come to be seen as "un-American,” one epidemiologist reportedly remarked (Baines 2005).

As journalist and medical writer Gina Maranto pointed out succinctly in a Scientific American article on the subject:

"Physicians, radiologists, statisticians and public health officials have made claims and counterclaims and with sometimes startling emotion have accused one another of misreading or misrepresenting data, of performing faulty analysis and of perpetuating myths that have dire consequences for women. Some specialists, as well as cancer societies, women's health advocates and manufacturers of mammography machines, have argued that mass screening saves lives; others on the clinical front lines and in policy-setting roles have contended that  evidence from a number of randomized controlled trials does not support such a claim" (Maranto 1996).

The National Institutes of Health, the National Cancer Institute and most of the other public agencies charged with formulating recommendations for screening based on scientific evidence routinely go out of their way to discredit studies that cast doubt on the usefulness of mass mammography screening. Mammography  is a cornerstone of the American ‘war on cancer.' That these national policy makers cannot even bring themselves to publicly acknowledge misgivings about the procedure, much less to re-examine their recommendations in the light of the alarming truth about the mammography paradox is little short of staggering.

Over-diagnosis is an acknowledged problem with screening mammography, leading to treatment that for some people may be both unnecessary and intrinsically damaging in its own right. The danger of a false positive reading, with all the attendant anxiety and ensuing interventions, is also always a risk in current screening mammography programs. Similarly, the real possibility of a false negative – a clean bill of health that turns out to be illusory – is inherent in screening mammography. Moreover, there is no guarantee whatever that a breast cancer identified by screening mammography will be curable.

Furthermore, as we have seen, for some premenopausal women, particularly those with node-positive disease, there is the additional danger that early diagnosis by means of mammography may actually reduce survival rather than extend it. It is worth noting that mammography screening for premenopausal women is not recommended in any other country except the US.

For older (postmenopausal) women, the benefits of mammography may be marginally greater, at least over time, although here again, there is a danger of over-diagnosis, and of high false positive (and negative) results.

Meanwhile, the debate over screening mammography continues unabated. The US medical profession continues to stand unwaveringly behind its recommendation that women aged 40 and up should undergo annual mammography. Just last month, for example, the New England Journal of Medicine (NEJM) published a paper that made headlines all over the world. It claimed that mammography had been proven responsible for saving lives from breast cancer. It is therefore worth examining this report a bit more closely.

It should be borne in mind that this was not actually a new clinical trial. Instead, this study was based on what are called "computer modeling techniques" (i.e., statistical inferences and predictions based not on direct observations of patients but on computer simulations). These techniques were used to re-analyze seven prior studies of the effectiveness of mammography. In addition, no modifications or allowances were made in order to achieve consistency between the seven studies. Five out of the seven studies showed that mammography had contributed less to the decline in death rates than had improvements in treatment.

The most vocal proponents of screening mammography tend to claim that screening reduces the death rate by anywhere from 45 percent to 64 percent. However, in this study screening mammography was only found to have contributed approximately 15 percent to the decline in death rates from breast cancer, while improvements in treatment were found to have contributed approximately 19 percent (Berry 2005).

The usefulness of this study, and the validity of its conclusions, are further undermined by the fact that the sample population spanned the entire age range, from 30 to 79 years. No attempt was made to separate women into different age groups. As Professor Cornelia Baines of the University of Toronto pointed out, this is a particularly important omission since the natural history of the disease varies widely in different age groups. For women in the age group 30-49, mammography’s benefits are the most questionable of all – a fact that was entirely ignored by this study (Baines, personal communication).

Yet despite this latest favorable NEJM article and despite the incessant repetition of the "mammography saves lives” mantra, there is, astonishingly, still no consistent, substantial scientific evidence that regular mammography results in a significant reduction in mortality from breast cancer. In an important paper published in 2000 in the prestigious journal Lancet, Swedish researchers, working on behalf of the international Cochrane Review organization, reviewed the quality of the major mammography trials to date and came to the following conclusions:

"Screening for breast cancer with mammography is unjustified.  If the trials are judged to be unbiased, the data show that for every 1000 women screened biennially throughout 12 years, one breast cancer death is avoided whereas the total number of deaths is increased by 6" (Gotzsche 2000).

In a paper examining the contradictory evidence concerning mammography screening, Steven Goodman, MD, a biostatistician at the Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, has written:

"If we take a step back, this controversy looks almost Swiftian when we consider that even under the most optimistic assumptions, mammography still cannot prevent the vast majority of breast cancer deaths…. There will come a time when all the study patients have been followed up, all the analyses have been done, all the expert groups have met, and all the editorials have been written, and we still won’t be sure how much benefit and how much harm are caused by mammography. We must find good ways to help women deal with this uncertainty, for that time is imminent" (Goodman 2003).

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