Atelier Kraemer

Posts Tagged ‘National Cancer Institute’

Posted on: 06.29.2015

Mammography’s Shadows, VII: Legacies

by Sylvia Kraemer
No Comments »

Tags: , , , , , , , ,


Posted in Healthcare, Uncategorized

Crab ImageGood science gives the same answer to questions posed by both male and female investigators.  But good science normally only answers questions as they are posed.  In the case of breast cancer, ordinarily only females experience the disease, with its attendant costs to themselves—and opportunities for others.  The same is true for current breast cancer detection practices, which rely primarily on screening x-rays (mammography).

This reality is illustrated in the commentary published in the British Medical Journal on the 2014 article summarizing the 25 year follow-up of the Canadian National Breast Cancer study.  The comments—all from men—focused, with one exception,[1] on the methodological and numerical minutiae of various randomized control trials and population-based investigations of the relationship of mammography screening and mortality from breast cancer.  As for risks–overdiagnosis and radiation-induced cancer in later years–virtually nothing was said.

By assessing methods of breast cancer detection or treatment solely within the limited epistemic confines of quantitative measures of breast cancer detection and mortality, we neglect the single most compelling constant of all:  the irradiation of women’s breasts and mid-sections for screening, diagnosis, and treatment.

The American Cancer Society (ACS) assures screening participants that mammography’s radiation dose is 0.4 millisieverts for “the typical mammogram with 2 views of each breast.” It adds that Food and Drug Administration regulations ensure that  the “radiation dose is required to be very low.”[2]  [See Baconspromise.org post IV, “Hunting Cancer with X-Rays.”]  The society also compares a woman’s x-ray exposure from a mammogram to “about the same amount of radiation she would average from her natural surroundings over about 7 weeks.”  This comparison obscures the fact that at any given time mammography exposures represent net increments to exposures from a woman’s natural surroundings.

When the ACS and the American College of Radiology further assure women that, despite its “risks,” screening mammography has been shown to have “benefit,” most women will infer that the “benefit” being referred to is a reduced risk of death from breast cancer.  After all, “mammography saves lives.”  Alas, it is not so simple.

For regulatory purposes the Food and Drug Administration defines mammography’s “benefit”as “the quality of the resulting radiograph[s].”[3]  Meanwhile, since x-ray  image quality is directly proportional to the radiation dose, improvement in mammography “benefit” has occurred along with a gradual increase in mean glandular dose per image to over four times the amount of exposure claimed by the American Cancer Society.[4]

The FDA’s own surveys of trends in mammography dose and image quality have found that the typical four image mammogram entails a mean x-radiation exposure of over 7 milligrays, or almost 18 times the amount advertised by the ACS.  (This does not take into account repeated images that may be taken during the same mammography session for the benefit of the radiologist attempting the most accurate reading.) Meanwhile, the FDA’s regulatory upper dosage limit for standard mammography equipment is 3.0 milligrays per exposure, or a total of 12 milligrays for the four exposures of the typical screening mammogram.[6]

Radiology technicians naturally make every effort to minimize radiation exposures.  But they must also make every effort to ensure the best possible image for the waiting radiologist, and the reality is that standard FDA-compliant equipment is able to direct much more radiation during a mammography than the limits the ACS suggests.

These higher levels of radiation are delivered with repeat or diagnostic mammograms, which are involved in breast biopsies performed whenever a woman’s screening mammogram produces “suspicious” results.  According to one recent estimate, such biopsies are done “about 1.6 million” times a year.[7]

A recent analysis of the insurance records of 700,000 women between the ages of 40 and 59 found that all had had routine screening mammographies, 11% of which were regarded as “suspicious” and thus resulted in repeat mammograms, ultrasounds and needle biopsies.  Except for the ultrasounds, the additional testing resulted in considerable additional x-radiation exposure.  Less than 2% of these follow-on procedures confirmed cancer.[8]  Repeat screening mammography, often within days of the initial exposures, has reportedly increased with the transition to digital mammography.[9]

Precise numbers for the frequency with which women are brought back for repeat mammograms are probably unobtainable.   Combing through proprietary records of radiology departments and insurance claims would be a daunting task.  That being so, assurances that the x-radiation exposure from mammography is too small to worry about—or “worth the risk”—are meaningless.

Perhaps the most insidious consequence of efforts to assure women that the radiation risk from mammography is “low,” is that such statements, and any comparative numbers offered to support them, invite women to infer that there is a safe threshold for x-radiation exposure, and that “low” is meaningful with reference to that threshold.  But there is no such thing as a safe threshold.

In 1955 the National Academy of Sciences created a committee on the biological effects of atomic radiation to review what had been learned from laboratory science and the findings of the Atomic Bomb Casualty Commission, formed in late 1945 to assess the radiation consequences of the bombings of Nagasaki and Hiroshima.

The committee issued an initial assessment in 1956, which was updated for its 1960 report.[10] The sub-group examining genetic effects confirmed that irradiation of female mice produced genetic damage. (That x-rays damage chromosomes, and are thus capable of producing tumors, had been shown by Theofore Heinrich Boveri before World War I.) It also confirmed genetic consequences for the “children of survivors of the atomic bombings at Hiroshima and Nagasaki,” as well as “children elsewhere whose parents received radiation for medical or other reasons.”[11]  However, cautioned the report,

. . . most of the man-made radiation to which the population of the United States is exposed involves dose rates not yet adequately investigated experimentally. For example, we do not know whether the effects of low doses given at high dose rates, as in medical exposures, will be more like the response from acute irradiation or more like that from chronic irradiation.”

Pathologies such as skin cancer and leukemia may result from “relatively low level” exposure “from time to time over a period of years. . . .” and it is “characteristic” of radiation that its “effects may manifest themselves not only immediately, but perhaps only after a long period of intermittent . . .exposure.”[12]

Delayed manifestation of biological effects results from the fact that . . .all types of induced and spontaneous tumors appear not to arise at once . . . . There is much evidence indicating that malignant change ordinarily develops only after a series of ‘precancerous’ changes or a state of tissue disorder has taken place.                  

The committee cautioned against predicting “human tumor incidences from small radiation doses based on extrapolation from the observed incidences following high dosage,” such as those recorded after the atomic bombings of Japan.  Furthermore, prediction—        

  . . .requires evaluation of the possibility that there is a threshold dose below which there is no probability of inducing leukemia, a concept which implies a factor of safety that would be most reassuring to those who are exposed to radiation in excess of the natural background . . . . However, no member of the Subcommittee feels that he can estimate the size of the threshold or, for that matter, even prove its existence. . . . The detailed information available . . . argues Strongly against a DNA repair-mediated low-dose threshold for cancer initiation. [13]   

Subsequent reports from the National Academy of Sciences’ Committee to Assess Health Risks from Exposure to Low Level Ionizing Radiation have affirmed this conclusion, viz. “it is prudent to assume that there is no threshold.”[14]

It is a truism that we usually get answers only to the questions we ask.  So let us enlarge the limited frame of reference for most randomized control trials or population-based studies of screening mammography’s merits, in three ways:

First, begin a population based inquiry in 1950, prior to the adoption of screening mammography [See Table 3], to detect larger “before” and “after” patterns requiring explanation.  This, as we have seen, the National Cancer Institute has already begun to do in order to examine whether the earlier diagnosis of breast cancer has, in fact, made a difference in the overall rate of breast cancer incidence. (See Blog Post VI, “The National Cancer Institute Weighs In.”)

Secondly, if we are serious about learning the risks of mammography screening, we will examine data reflecting changes in the incidence of conditions that are known to be susceptible to x-radiation, for example, (a) other forms of cancer, especially originating in the chest area, such as the thyroid glands, trachea, bronchus and lungs, and (2) heart and cardiovascular disease.

Thirdly, we can focus on those ages in which mortality from cancer and heart disease are most pertinent, viz., over the age 45.  Nature has provided us with a perfect comparison group for women confronted with these diseases:  men.

The National Center for Health Statistics collects and maintains the largest and most comprehensive data on health in the United States, data which goes as far back as 1950.  And it does so using analogous definitions, collection procedures, and statistical methods across all measures of health and disease.

If one compares deaths from malignant neoplasms of the trachea, bronchus and lungs for both men and women 45 years and older, over the six decades between 1950 and 2010, one cannot but be struck by the continued increase of female mortality from those diseases beginning in 1980, and especially after 1990, when corresponding male deaths began to decline precipitously. [See Table 1 ] (The same dramatic disparity is evident between men and women after the age of 65.)  This disparity cannot be blamed on smoking. [See Table 2]

Meanwhile, the incidence of thyroid cancer has increased more than twice the rate in women than in men since 1991, with increases being larger among white women, who are more likely to have received screening mammograms.  In the early 1970s, rates of thyroid cancer among women had begun to hold steady (black women) or decline (white women).  An increase in the rates for both white and black women becomes evident in the 1980s and 1990s and does not reverse before 2011, year of the most recent SEER data.[15]

Then there is cardiovascular disease.  During the three decades after 1950 the death rate from heart disease (or cardiovascular disease, CVD) in the United States for women 65 years and older remained the same, at about 300 per 100,000.  Substantially more men 65 and older died from heart disease during that period, though their death rate improved significantly (from 425 to 377 per 100,000) in 1977.  At the end of the 1970s appreciably fewer women of all ages were dying from cardiovascular disease than men.

By 1980 something changed.  Deaths from cardiovascular diseases among women began to approach CVD deaths among men, surpassing the rate for men in four years.  Indeed the numbers of men dying from cardiovascular disease began to decline after 1980, while the death rate for women continued to increase.

For a brief period (1990-1995) the CVD death rate for both men and women of comparable ages increased slightly, but in 1995 the rate resumed its decline for men.  Women’s CVD death rate not only increased more sharply during 1990-1995, but continued to increase until 2000.  Then their CVD death rate also began to decline, even more sharply than the rate for men.  By 2010 the disparity in CVD death rates for men and women was the smallest since 1985.[16] [See Chart – CVD Mortality Trends]

Nearly half (47%) of the decrease in age-adjusted mortality from cardiovascular disease among men and women by 2000 has been attributed  to improved treatments, with the remaining improvement attributable to reductions in risk factors, such as smoking and physical inactivity.[17]  Nonetheless, in spite of improvements in the treatment of both cardiovascular disease (CVD) and cancer, in 2010 a woman over the age of 45 was twelve times as likely to die from CVD as from breast cancer.[18]

Common explanations for the post-1980 disparity in CVD mortality between men and women are that “women have smaller hearts and smaller arteries,” their hearts beat faster and 300 million more times in a lifetime than men’s hearts, while women’s heart rate dynamics are more variable and complex. What’s more, tobacco use is supposedly more dangerous in women.[19] However, such reasoning does not explain why fewer women than men died from heart failure for the three decades between 1950 and 1984.

Finally, let’s return to the possibility that some breast cancers that occurred, recurred, or metastasized  among women in their 50s through 70s did so as a result of cumulative x-ray exposures from diagnostic or therapeutic mammography.  A rereading of the National Cancer Institute’s attempt to quantify “overdiagnosis” in its 2015 guidance for physicians inadvertently raises this question.

For any given number of women over the age of 40, a certain number of breast cancers is likely to occur. Thus increases in early detection should be accompanied by corresponding decreases in breast cancer detection in later years. [20]  Accordingly, the NCI examined “several observational population-based studies” that compared “breast cancer incidence before and after adoption of screening.”

If mammography screening were as effective as its proponents promise,

. . . there would be a rise in incidence followed by a decrease to below the prescreening level and the cumulative incidence would be similar.  Such results have not been observed.  Breast cancer incidence rates increase at the initiation of screening without a compensatory drop in later years. . . .  A population-based study showed increases in invasive breast cancer incidence of 54% in Norway and 45% in Sweden in women aged 50 to 69 years, following the introduction of nationwide screening programs.  No corresponding decline in incidence in women older than 69 years was ever seen.  Similar findings . . . have been reported from the United Kingdom and the United States.

The NCI attributes these findings to “overdiagnosis.”  But they could also reflect the induction of breast cancer by the cumulative exposure of women’s breasts to x-radiation.  We cannot know how many of those later incidences of breast cancer are radiation-induced, but the fact that they do occur is a serious and troubling outcome, especially for older women.

*   *   *

šIf numbers provide an inadequate foundation for establishing medical protocols, it is because statistical correlation is too readily confused with causation, and because those aspects of biological phenomena that can be captured by quantities do not replicate biological processes over time—which carcinogenesis certainly is.

For some the “gold standard” of evidence in medicine is the randomized control trial.  For others, scientific proof entails not only quantification, but replicability.  But numbers cannot replicate biological processes, nor can we completely replicate in the laboratory the etiology of disease in a given group of persons.  Still, numbers—especially in epidemiology—do have the power to capture evidence of trends, and thus to pose questions that might not otherwise be raised as a result of cultural bias, or economic interest.

So it is that we must question the ethics of continuing to subject the upper torsos of women asymptomatic and at low-to moderate risk to breast cancer to cumulative and repeated exposure of even low-levels of ionizing radiation without compelling and justifying reasons, applicable and acceptable to each individual patient.  Compounded by the continuing and larger radiation exposures involved in over-diagnosis and over-treatment, the ethics of policies that promote widespread screening mammography beg to be challenged.

Screening mammography remains an experiment.  We are learning the amount and costs of over-diagnosis and over-treatment.  Given the complexity of possible additional health risks from the practice, the likelihood of providing sufficient reliable information to obtain genuinely informed consent to mammography is remote. Therefore, before continuing to consider routine screening mammography as appropriate for all women of any age we must also eliminate it as a contributor to disparate disease trends among adult men and women, as well as a source of recurring or new breast cancers.

(This is the concluding post in a seven part series on the unknowns of routine screening mammography for asymptomatic and low-to moderate risk women. As a result, screening mammography remains a medical experiment. The complexity of the unresolved questions mean that genuinely informed consent to the procedure is highly unlikely. Posted June 29, 2015.)

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

[1] Donald J. Benjamin, “Comment re. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: Randomised screening trial,” British Medical Journal (11 February 2014), http://www.bmj.com/content/348/bmj.g366, Downloaded March 2, 2015.

[2] American Cancer Society, “Radiation exposure from mammography,” http://www.cancer.org/treatment/understandingyourdiagnosis/ examsandtestdescriptions/mammogramsandotherbreastimagingprocedures/ mammograms-and-other-breast-imaging-procedures-mamm-radiation. Downloaded March 3, 2015.  The sievert is a derived unit in the International System of Units which, when applied to human radiation exposure, incorporates an estimate of the probability of cancer induction or genetic damage. 1 milligray is conventionally considered equivalent to 1 millisievert.

[3] David C. Spelic, “Dose and Image Quality in Mammography: Trends during the First Decade of MQSA,” http://www.fda.gov/Radiation-EmittingProducts/MammographyQualityStandardsActandProgram/ FacilityScorecard/ucm113606.htm.  Downloaded March 3, 2015.

[4]  The specific FDA amounts are 1.5 milligrays in 1995 and 1.76 milligrays  in 2003. The milligray is the metric measurement unit of absorbed radiation dose of ionizing radiation, e.g., x-rays.  For FDA findings, see David C. Spelic, “Dose and Image Quality in Mammography: Trends during the First Decade of MQSA,”http://www.fda.gov/RadiationEmittingProducts/Mammography QualityStandardsActandProgram/FacilityScorecard/ucm113606.htm.  Downloaded March 3, 2015.

[5] 1990 Recommendations of the International Commission on Radiological Protection (ICRP Publication 60). (Oxford: Pergamon Press, 1991).

[6] Food and Drug Administration, Mammography Quality and Standards Act Regulations, (67 FR 5446), Subpart B, Section 900.11 (e)(5)(iv)-(x), http://www.fda.gov/Radiation-EmittingProducts/ MammographyQualityStandardsActandProgram/ Regulations/ucm110906.htm.  Downloaded March 3, 2015.

[7] Joann G. Elmore, et al., “Diagnostic Concordance Among Pathologists Interpreting Breast Biopsy Specimens,” Journal of the American Medical Association, Vol. 313, No. 11 (March 17, 2015), pp.1122-1132.

[8] Mei-Sing Ong and Kenneth D. Mandl, “National Expenditure for False-Positive Mammograms and Breast Cancer Overdiagnoses Estimated at $4 Billion A Year,” Health Affairs, Vol. 34, No. 4 (April 2015), pp. 576-583.

[9] Denise Grady, “In Shift to Digital, More Repeat Mammograms,” The New York Times (April 20, 2008).

[10] National Academy of Sciences-National Research Council, The Biological Effects of Radiation:  Summary Reports (Washington, DC: 1960).

[11] National Academy of Sciences-National Research Council, The Biological Effects of Radiation:  Summary Reports (Washington, DC: 1960), p. 3.

[12] National Academy of Sciences-National Research Council, The Biological Effects of Radiation:  Summary Reports (Washington, DC: 1960), pp. 27-29.

[13] National Academy of Sciences-National Research Council, The Biological Effects of Radiation:  Summary Reports (Washington, DC: 1960), pp. 32-35.

[14] For example, “at the level of cancer-associated gene or chromosomal mutation, the presence of a true dose threshold demands totally error-free DNA damage response and repair.” National Academy of Sciences, Biological Effects of Ionizing Radiation, V (National Research Council, 1990),  National Academy of Sciences, Biological Effects of Ionizing Radiation, VII, Phase 2 (National Research Council,  2006), p.245.

[15] National Cancer Institute, “A Snapshot of Thyroid Cancer.” http://www.cancer.gov/researchandfunding/progress/snapshots/thyroid;  National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) Program, FastStats, Table 26.3.  Downloaded April 14, 2015.

[16] Alan S. Go, MD, et al., “AHA Statistical Update: Heart Disease and Stroke Statistics—2014 Update: A Report From the American Heart Association,” Circulation, Journal of the American Heart Association (December 18, 2013); Source: National Center for Health Statistics:  “Health, United States, 2012,” Hyattsvile, MD (2013); National Center for Health Statistics, “Health, United States, 2010, With Special Feature on Death and Dying” (Hyattsville, MD., 2010).

[17] Earl S. Ford, MD., et al., “Explaining the Decrease in U.S. Deaths from Coronary Disease, 1980-2000,” New England Journal of Medicine, Vol. 356 (June 7, 2007), pp. 2388-2398.

[18] National Center for Health Statistics:  “Health, United States, 2012,” Hyattsvile, MD (2013); National Center for Health Statistics, “Health, United States, 2010, With Special Feature on Death and Dying” (Hyattsville, MD., 2010).

[19] See, for example, Hope Ricciotti, MD, “Heart Disease – Differences Between Men and Women,” Beth Israel Deaconess Medical Center. http://www.bidmc.org/Centers-and-Departments/Departments/Medicine/ Divisions/Cardiovascular-Medicine/For-Patients/Your-Heart-Health/Tips-for-Heart-Health/Heart-Disease—Differences-Between-Men-and-Women.aspx. Downloaded March 17, 2017, and Mike Zimmerman, “Heart Disease: Lifesaving News,” AARP: The Magazine (April-May, 2014).

[20] National Cancer Institute, “Breast Cancer Screening (PDQ®): Harms of Screening Mammography: Overdiagnosis,” Update: February 6, 2015. http://www.cancer.gov/cancertopics/pdq/screening/breast/healthprofessional/page8. Downloaded February 25, 2015.

 

Post to Twitter Tweet This Post

Posted on: 06.18.2015

Mammography’s Shadows, VI: The National Cancer Institute Weighs In

by Sylvia Kraemer
No Comments »

Tags: , , , , ,


Posted in Uncategorized

Crab Image

Like all federal agencies the National Cancer Institute is subject to indirect political pressure through congressional and executive branch control of agency budgets.  Such pressure can and does influence programmatic decisions. That had been the case with the Breast Cancer Demonstration Project of the 1970s (see this blog’s post for May 25, 2015, “Mammography’s Shadows: The Campaign,”).

But thanks to federal commercialization policy, which prohibits government agencies from competing in the market for commercially available products and services, neither the institutional survival of federal mission or regulatory agencies, nor their employees’ job security, depends on revenue streams from medical procedures, equipment, and pharmaceuticals. Moreover, the science intensive agencies, such as the National Institutes of Health, supplement their internal scientific capabilities with advisory groups and consensus conferences of outside researchers, while those agencies reserve to themselves the duty of final arbiter of disputed research findings.

Thus it should not be surprising that the National Cancer Institute’s own positions on the benefits and risks of screening mammography might vary from those taken by the American Cancer Society and Memorial Sloan Kettering Cancer Center.  When reporting on screening mammography in the framework of its parent agency’s (National Institutes of Health) goals for its “Healthy People Program”[1], a programmatic document,  the NCI cautiously endorsed widespread screening mammography.

But it did so with subtle differences, noted here in italics: In 2012 the institute wrote  biennial “mammography screening allows for the early detection of breast cancer, which may help reduce mortality from breast cancer, especially among women aged 50 to 69 years.”  For these women “there is solid evidence that screening may lower this risk by up to 30 percent.  For women in their 40s, the [mortality] risk may be reduced by about 17 percent.  For women aged 70 and older, mammography may be helpful, although firm evidence is lacking.”[2]

In the NCI’s subsequent breast cancer screening guidance for health professionals, however, the federal cancer agency explicitly relied on the comprehensive ‘physicians data query (PDQ®)’ research database.  This evidence-based foundation, in contrast to the policy goals of the NIH, supported a much different construction. Well over half of the 38 research reports referenced in the guidance were published after 2000, none was published prior to 1990, and missing are citations to the “large randomized trials conducted a generation or more ago” upon which Memorial Sloan Kettering claimed it based its own mammography screening guidance.

Noticeable by its repeated appearance among the published research reports referenced by the NCI is the work of H. Gilbert Welch, Professor of Medicine at Dartmouth’s Geisel School of Medicine, and Peter C. Gøtzsche of the Nordic Cochrane Center, and their co-investigators.  Since the early 1990s Welch in particular has been calling attention to screening mammography’s hazards of over-diagnoses and over-treatment.[3]

Peter C. Gøtzsche, meanwhile, has been a thorn in the side of routine mammography screening advocates, because the Cochrane group’s rigorous meta-analyses of randomized controlled trials in medicine have failed to support the claim that screening mammography reduces breast cancer mortality, while also suggesting it results in significant over-diagnoses and over-treatment.[4]  In a debate about the health of women’s bodies dominated overwhelmingly by men, it’s noteworthy that two laudatory forwards to Gøtzsche’s 2013 book were written by women, the President of the National Breast Cancer Coalition (Fran Vesco) and President of the Royal College of General  Practitioners (Iona Heath).

The NCI evaluated screening mammography research studies on the basis of both their internal validity (reliability of cause-effect relationship, elimination of confounding variables) and external validity (generalizability beyond populations studied).[5]  In the February 2015 update to its December 2014 health professionals’ review of breast cancer screening, the NCI analyzed research findings as they would apply to 10,000 women who undergo annual screening mammography (a) for women in their 40s, 50s and 60s, and (b) extending over two time periods, 10 years and 15 years.  Given cancer latency which can reach beyond 10 years, the longer time periods are important.

The institute’s research analysts found that the best estimates of cancer deaths averted over the next 15 years for women in their 40s attributable to screening mammography did not exceed .16% (or 16 out of 10,000).  That percentage increased slightly for women in their 50s (at most .32% or 32 out of 10,000) and again for women in their 60’s (at most .49% or 42 out of 10,000).  At no time did the estimates approach 1%.

At the same time, the best estimates of the false-positive results during a ten year period reached minimums of 59% (5,940 out of 10,000) for women in their 40s, 58% for women in their 50s, and 48% for women in their 60s.[6]  False-negative results occur as well, and no doubt the fear of that result accounts for what the NCI concluded was the “biggest risk factor for having a false positive mammogram,” namely “the individual radiologist’s tendency to read mammograms as abnormal.”[7]

Especially valuable was the NCI’s effort to wrestle with the question of over-diagnosis, or the diagnosis and treatment of cancers over the 10 year period that would never have become clinically significant.  Since “cancers that will cause illness and/or death cannot be confidently distinguished from those that will remain occult . . . all cancers are treated.”  But an effort to assess the extent and circumstances of over-treatment is critically important to those women suffering through treatment unnecessarily, albeit generating revenue for those furnishing it.

The NCI approached this question by examining studies comparing breast cancer incidence before the introduction of screening mammography, and afterwards.  If mammography screening has an appreciable effect, the incidence of cancer detected in a population should increase during the early years of screening, but then the incidence should decline in later years.  This would result from cancers having been found earlier that would have been palpable only in later years.

What the NCI analysis of population-based screening data from studies in Norway, Sweden, the United Kingdom, and the United States found was that “breast cancer incidence rates increase at the initiation of screening without a compensatory drop in later years.”

One study in 11 rural Swedish counties showed a persistent increase in breast cancer incidence following the advent of screening.  A population-based study showed increases in invasive breast cancer incidence of 54% in Norway and 45% in Sweden in women aged 50 to 69 years, following the advent of screening.  No corresponding decline in incidence in women older than 69 years was ever seen.[8]

While couched in terms of evidence of possible over-diagnosis, the NCI’s analysis of trends in breast cancer incidence before and after the introduction of screening mammography is an important step toward liberating the debate over mammography screening from the very narrow epistemic and conceptual confines within which it has been conducted over the past half-century.

First, measuring the value of screening mammography entirely in terms of “early treatment saves lives,”  limits the question to mortality data, which seems certain and definite.  But the reporting of deaths and determination of their causes is not an exact or detached science, especially when applied to older persons.[9]  Secondly, while male physicians naturally incline to the heroic aspiration to preserve life (postpone death), those female patients who must suffer through ultimately unsuccessful breast cancer treatment may prefer quality of life over its duration.  But those patients are unlikely to know at the onset how long their treatment must be endured and whether it will succeed.

Secondly, the mantra “early detection saves lives” assumes that we know enough about the causes and optimal treatments for various breast cancers to fulfill the promise of “early detection.”  This assumption becomes critical to the validity of all statistically based arguments for screening mammography:  it requires that breast cancer treatment for all women is a constant and thus neutral factor, when it In fact is a critical and unstable variable.

One of the few comments responding to the Canadian National Breast Cancer Study published in the British Medical Journal (2014) that did not get ensnared in numbers generated by randomized control trials came from Donald L. Benjamin, a researcher at Australia’s Cancer & Support Society.  Benjamin’s own research into the efficacy of surgery for breast, bowel, lung, prostate and ovarian cancer (research also based on randomized controlled trials) led him to conclude that breast cancer is a systemic disease, and its tumors are symptoms rather than its causes.[10]  While this is not a new insight, its truth confounds efforts to reduce standard modes of breast cancer detection and mortality to simple comparative numbers.

The appreciation of breast cancer’s systemic character has had a substantial effect not only on determining risk (e.g., the presence of biomarkers such as mutations of the BRCA1 and BRCA2 genes in families experiencing unusual levels of breast and ovarian cancers[11]).   Our increased understanding of the role of estrogen receptors (ER) in breast cancer has led to successful endocrine therapies using tamoxifen, an ER suppressor, and aromatase inhibitors that block the enzymes that convert androgens into estrogens.[12]  How effective these therapies are, and their side-effects, continue to be examined, as they should be.

In short, understanding how breast cancer works is an ongoing process, and breast cancer therapies are not fixed in time, nor are their results for all women constant or uniform. Thus the most important variable in efforts to link screening mammography and breast cancer mortality is the etiology of breast cancer in individual women.  Treating breast cancer morbidity as a neutral constant, as one attempts to establish a linear relationship between tumor phase at detection and breast cancer mortality, is the most serious weakness in all quantitative justifications for screening mammography.

Thirdly, by assessing methods of breast cancer detection or treatment solely within the limited epistemic and conceptual confines of breast cancer itself, we neglect the single most compelling constant of all:  the irradiation of women’s breasts, with inevitable x-ray scatter to the torso during mammography screening, diagnostic mammography, and radiation treatment.

This has turned out to be a very high risk to take, all in order to spare women of any age from breast cancer deaths at the rate of less than on-half of one percent per 10,000.

(Published June 18, 2015.  Our next and final post in the “Mammography’s Shadows” series looks at the now apparent consequences for untold women of their cumulative annual exposures to breast x-rays.  It also notes that it was women, not only because of the nature of their disease but because of cultural attitudes, who were persuaded to participate in this long-term and hazardous medical experiment.)

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

[1] See: http://www.healthypeople.gov/2020/about/History-and-Development-of-Healthy-People.

[2] The federal Healthy People 2010, 2020 target is biennial mammography screening for 70% of all women over 40, a target that was met only briefly in 2003. National Cancer Institute, “Cancer Trends Progress Report-2011-2012 Update: Breast Cancer Screening.” http://progressreport.cancer.gov/ doc_detail.asp?pid=1&did=2011&chid=102&coid=1016&mid=. Downloaded March 9, 2015.

[3] See, for example, H. Gilbert Welch, Should I be Tested for Cancer?: Maybe Not, and Here’s Why (University of California Press, 2006), and H. Gilbert Welch, “Breast Cancer Screenings: What We Still Don’t Know,” The New York Times (Dece,ber 29, 2013).

[4] See Donald G. McNeil, Jr., “Confronting Cancer: Scientist at Work — Peter Gotzsche: A Career That Bristles With Against-the-Grain Conclusions,” The New York Times (April 9, 2002), and Gøtzsche, Peter C. Mammography Screening: Truth, Lies and Controversy. (Radcliffe Publishing Ltd., 2012).

[5] National Cancer Institute, “Breast Cancer Screening (PDQ ®): Health Professional Version,” (December 5, 2014). http://www.cancer.gov/ cancertopics/pdq/screeningbreast/healthprofesional/.Downloaded December 20, 2014).

[6] National Cancer Institute, “Breast Cancer Screening (PDQ®): Harms of Screening Mammography,” Update: February 6, 2015. http://www.cancer.gov/cancertopics/pdq/screening/breast/healthprofessional/page8. Downloaded February 25, 2015.

[7] National Cancer Institute, “Breast Cancer Screening (PDQ®): Harms of Screening Mammography,” Update: February 6, 2015. http://www.cancer.gov/ cancertopics/pdq/screening/breast/healthprofessional/page8. Downloaded February 25, 2015.

[8] National Cancer Institute, “Breast Cancer Screening (PDQ®): Harms of Screening Mammography: Overdiagnosis,” Update: February 6, 2015. http://www.cancer.gov/cancertopics/pdq/screening/breast/healthprofessional/page8. Downloaded February 25, 2015.

[9] See for example, Kathryn Schulz, “Final Forms:  What Death Certificates Tell us, and What They Don’t,” The New Yorker (April 7, 2014), pp. 32-37.

[10] Donald L. Benjamin, “Comment re. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: Randomised screening trial,” British Medical Journal (11 February 2014), http://www.bmj.com/content/348/bmj.g366, Downloaded March 2, 2015; DonaldJ. Benjamin, “The Efficacy of Surgical Treatment of Cancer-20 Years Later,” Medical Hypotheses Vol. 82 (2014), pp. 412-420.

[11] BRAC1 and BRCA2 are human genes and their proteins that participate in the repair of damage to the chromosomes and DNA, and the destruction of cells with damaged DNA.

[12] Monica Morrow, MD, “50 Years in Breast Cancer: Dramatic Progress in Treatment Based On an Improved Understanding of Biology,”  Annual Meeting of the American Society of Clinical Oncology, 2014. http://am.asco.org/50-years-breast-cancer-dramatic-progress-treatment-based-improved-understanding-biology. Downloaded  January 3, 2015.

Post to Twitter Tweet This Post

Posted on: 06.17.2015

Mammography’s Shadows, V: The Doctrine Unravels

by Sylvia Kraemer
No Comments »

Tags: , , , , , ,


Posted in Healthcare

Crab ImageThe American Cancer Society continues to advise “women age 40 and older” to have a mammogram “every year and should continue to do so for as long as they are in good health.” Most privately operated medical institutions in the United States, reliant as they are on revenue streams from diagnostic and treatment procedures, echo the ACS’s guidance. [1]

Like the American Cancer Society, Memorial Sloan Kettering Cancer Center (for example) recommends annual screening mammography for asymptomatic women of “average-risk” beginning at age 40.  The screening guidelines section on MSKCC’s website proclaims “studies have shown that regular screening of women with no symptoms has decreased the number of women who die from breast cancer approximately 45 percent.”[2]  Those studies are not cited.

It is a sad testament to the reliability of medical guidelines emanating from the U.S. healthcare system that such institutions as the ACS and MSKCC continue to advocate annual screening mammography for asymptomatic women of average risk, even though the research fabric supporting the notion that screening mammography saves lives has thoroughly unraveled.  The power of private sector medical revenue streams to influence such guidelines is suggested by the responses of various organizations to the United States Preventative Services Task Force breast cancer screening guidelines, reissued in 2009.

The USPSTF guidelines, based on the most comprehensive meta-analysis of screening data done to date, recommended mammograms for women aged 40-49 only if they are at risk for breast cancer [emphasis added], and every one to two years after age 50.[3]  This revised schedule was widely criticized by medical organizations with a vested interest in the continuation of X-ray breast cancer screening.[4]

Most fierce in their resistance to the USPTF’s revised guidelines were American College of Radiology (ACR) and the Society of Breast Imaging, both medical trade associations:  “These unfounded USPTF recommendations,” alleged the ACR, “ignore the valid scientific data and place a great many women at risk of dying unnecessarily from a disease that we have made significant headway against over the past 20 years.”[5]

The Society of Breast Imaging (SBI) was less temperate, calling the USTPF recommendations “a step backward . . . shocking” and “a significant harm to women’s health.”  Like the ACR, the society defended regular mammograms for women beginning at 40 years as an “approach [that] has overwhelmingly been shown to save lives.”[6]

The National Cancer Institute, however, whose “primary role as a biomedical research agency is to generate scientific knowledge that can be used by the Task Force and other organizations in their deliberations and recommendations,” did not agree.  “Today’s report reflects the fact that more questions need to be answered.”  Neither did eleven other health care and cancer prevention organizations, who wrote the leadership of the U.S. House committee responsible for government oversight and public health:

The US Preventive Services Task Force was established as an independent body to apply rigor and objectivity to the analysis of clinical preventive care—even on issues that arouse passions and political posturing.  The misstatements we have noted are evidence of both of these dangers, and the Task Force is our best defense against both.[7]

What the disputed 50 year threshold for routine mammography for all women further revealed was that a compelling scientific case had not been made that mammography’s “risks outweigh its benefits” on either side of that age.  And, since most everyone who has lived longer than 50 years has noticed that biological and calendar age are not one and the same, the entire proposition of basing mammography screening on calendar age is problematic at the least.

The controversy continued when the British Medical Journal published, on February 11, 2014, a summary of the results of a twenty five year follow-up for breast cancer incidence and mortality by the Canadian National Breast Screening Study.  The article reported that the Canadian study, begun in 1980, after 25 years-

. . . found no reduction in breast cancer mortality from mammography screening in a programme offering five annual screens, neither in women aged 40-49 at study entry nor in women aged 50-59.  Although the difference in survival after a diagnosis of breast cancer was significant between those cancers diagnosed by mammography alone and those diagnosed by physical examination screening, this is due to lead time, length time bias, and overdiagnosis.[8]

Memorial Sloan Kettering’s deputy physician-in-chief for breast cancer programs was quick to denounce the Canadian study, claiming it was so “flawed” that “it should not influence any changes in screening recommendations.”[9]

If the Canadian study’s limitations–imperfect randomization, uneven skills among imaging technologists, and variable quality mammograms—invalidated its conclusions, then so also did those same flaws invalidate the HIP-GNY and BCDDP conclusions (see preceding posts).[10]  In any event, the BMJ article contains extensive discussion of these aspects of the Canadian study, concluding that “the lack of an impact of mammography screening on mortality from breast cancer in this study cannot be explained by design issues, lack of statistical power, or poor quality mammography.”[11]

Close on the heels of the British Medical Journal’s 2014 report of the Canadian study came “Abolishing Mammography Screening Programs? A View from the Swiss Medical Board,” published in the May 22, 2014 issue of the New England Journal of Medicine.[12]  If the Canadian study reported a few months earlier nudged at the conceptual boundaries of previous quantitative studies of mammography’s benefits, the Swiss group created a new outward salient.  No doubt this was partly a result of the wider disciplinary reach of the study group’s members, who included, in addition to physicians, a medical ethicist, a clinical epidemiologist, a nurse scientist, a lawyer, and a health economist.

The debate over mammography consists largely of “reanalyses of the same, predominantly outdated trials,” argued the Swiss group.  More importantly, the extent of over diagnosis (previously detected by the Nordic Cochrane Center’s analyses) reported in the Canadian study meant that over 100 women “were diagnosed with and treated for breast cancer unnecessarily, which resulted in needless surgical interventions, radiotherapy, chemotherapy, or some combination of these therapies.”  Here the Swiss group was amplifying the female patient-centered warnings of a growing minority of American physicians that annual mammography screening was subjecting numerous healthy women to unnecessary expense, emotional turmoil, invasive procedures, toxic treatments and risks from disfiguring surgery.[13]

The Swiss board further extended its recognition of those who had the most at stake in this controversy—women—by incorporating the findings of a four-country population based survey of women’s perception of the benefits of mammography screening.  That survey revealed that “in the US and three European countries a high proportion of women overestimated the benefits that can be expected from screening mammography.”

Whereas the women sampled believed that, without mammography screening, 20% of women would die of breast cancer within 10 years, the actual percentage was one-half of one percent, or .5%, who would die of breast cancer in that period.  “This finding,” concluded the survey, “raises doubts on informed consent procedures within breast cancer screening programmes [sic].” [14]

Still, that finding could also provide gratifying assurances to the American Cancer Society that its 30-year campaign to promote X-ray breast cancer screening among asymptomatic women had been a success.  That success could be confirmed by other numbers:  The proportion of women 40 years and older having mammographies within a 2 year period increased from less than 30% in 1987 to nearly 70% by 2000.  (Among women 50-64 years the increase nearly reached 80 %.)[15]

(Published June 17, 2015.  The next post looks at the National Cancer Institute’s review of the most recent research into the harms and benefits of screening mammography and the resulting update of its own guidelines.)

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

[1] Austin Frakt and Aaron E. Carroll, “If Patients Only Knew How Often Treatments Could Harm Them,” The New York Times (March 2, 2015).

[2] Memorial Sloan Kettering Cancer Center (MSK) in New York, founded in 1884, was one of the sites for the Breast Cancer Detection Demonstration Project and in 1996 it acquired the Guttman Institute founded in 1968 by Dr. Philip Strax, head of the Health Insurance Plan of Greater New York’s highly touted study of breast cancer screening.  Memorial Sloan Kettering Cancer Center, “Screening Guidelines” http://www.makcc.org/cancer-care/adult/breast/screening-guidelines. Downloaded March 2, 2015.

[3]http://www.uspreventiveservicestaskforce.org/Page/Topic/recommendation-summary/breast-cancer-screening.  Downloaded October 13, 2014. The U.S. Preventive Services Task Force, created in 1984 by the federal Agency for Healthcare Research and Quality, is an independent, volunteer panel of national experts in prevention and evidence-based medicine.  The guidelines included a recommendation that women not be taught breast self-exam, arguing that BSE was more likely to lead to “anxiety, unnecessary visits, imaging, and biopsies.”  In December, 2009, the USPTF updated its guidelines to read: “The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms.” US Preventive Services Task Force, “Screening for Breast Cancer,” Updated December 2009.  http://www.uspreventiveservicestaskforce.org/usptf/uspsbrca.htm (Downloaded September 9, 2014).

[4] NBC Nightly News, November 17, 2009.  http://www.nbcnews.com/video/nightly-news/34002015#34002015

[5] Quoted in  “Major Cancer Agencies Respond to USPTF’s New Mammography Guidelines,” Oncology Journal (December 15, 2009).

[6] Quoted in  “Major Cancer Agencies Respond to USPTF’s New Mammography Guidelines,” Oncology Journal (December 15, 2009)

[7] Quoted in  “Major Cancer Agencies Respond to USPTF’s New Mammography Guidelines,” Oncology Journal (December 15, 2009).  The organizations were the American Academy of Family Physicians, American Academy of Nurse Practitioners, American Academy of Physician Assistants, American College of Physicians, American College of Preventive Medicine, American Journal of Preventive Medicine, American Public Health Association, National Association of County and City Health Officials, Partnership for Prevention, and the Trust for America’s Health.

[8] Anthony B.Miller, Claus Wall, Cornelia J. Baines, Ping Sun, Teresa To, and Steven A. Narod, “Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial,” British Medical Journal (11 February 2014), http://www.bmj.com/content/348/bmj.g366, Downloaded March 2, 2015.

[9] Memorial Sloan Kettering Cancer Center, “In the News: Recent Study Should Not Change Mammography Guidelines” (February 12, 2014), http://www.mskcc.org/blog/recent-study-should-not-change-mammography-guidelines.  Downloaded March 2, 2015.

[10] Daniel B.Kopans and Stephen A. Feig, “The Canadian National Brfeast Screenoing Study: A Critical Review,”  American Journal of Roentgenology, Vol. 161 (October, 1993).

[11] Anthony B.Miller, Claus Wall, Cornelia J. Baines, Ping Sun, Teresa To, and Steven A. Narod, “Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial,” British Medical Journal (11 February 2014), http://www.bmj.com/content/348/bmj.g366, Downloaded March 2, 2015.

[12] Nikola Biller-Adorno, M.D., Ph.D. and Peter Jűni, M.D., “Abolishing Mammography Screening Programs? A View from the Swiss Medical Board,” The New England Journal of Medicine (May 22, 2014), pp. 1965- 1967.  Original report published February 2, 2014 on Swiss Medical Board website:  http://www.medical-board.ch/fileadmin/docs/public/mb/Fachberichte/2013-12-15_Bericht_Mammographie_Final_rev.pdf (Downloaded October 6, 2014).

[13] See, for example, Archie Bleyer, M.D., and H. Gilbert Welch, M.D., M. P. H., “Effect of Three Decades of Screening Mammography on Breast Cancer Incidence,” The New England Journal of Medicine (November 22, 2012), pp. 1998-2005.

[14] Domenighetti G., D’Avanzo B., Egger M., et al. “Women’s Perceptions of the Benefits of Mammography Screening: Population Based Survey in Four Countries.”  International  Journal of Epidemiology, Vol. 32 (2003), pp. 816-821.  Over 4,000 randomly sampled women in the United States, Italy, the United Kingdom, and Switzerland were surveyed.

[15] Source: Centers for Disease Control and Prevention, National Center for Health Statistics, http://www.cdc.gov/nchs/faststats/mamogram.htm, downloaded March 23, 2014.

Post to Twitter Tweet This Post

Posted on: 06.09.2015

Mammography’s Shadows, IV: Hunting Cancer with X-Rays

by Sylvia Kraemer
No Comments »

Tags: , , , , , , , , , , , ,


Posted in Healthcare, Science and Policy

Crab ImageAll of us come into the world designed by evolution to survive.  Failing some rare mishap, we arrive equipped with immune systems ready to do battle with unfriendly biologic mischief makers.  The wizards within us that enable this microscopic life-preserving enterprise reside in the nuclei of our 75-100 trillion cells.

Just as millions of  ‘0s’ and ‘1s’ arrayed in lines of computer code serve as the language  of a computer’s operations, a sequence  of roughly 100 millions of four different kinds of organic molecules, or nucleotides, arranged in pairs between two identical DNA strands, provide the  instructional language for our cells’ functions.  These lengthy strands (estimates range from about 3 to 5 feet) are wound in a double helix and folded over themselves repeatedly in order to fit within the chromosomes of cell nuclei, thanks to some very clever engineering work by proteins, our bodies’ ‘hard hats.’

DNA molecules  govern our  cells’ functions, their  development and their reproduction.  After a limited number of generations, they ensure cell  death  to make way for new cell growth.[1]   Cell reproduction requires that the two DNA strands separate and unwind (more work for proteins), each strand then directing the synthesis of a new, identical partner.  The new, double stranded DNA in the new “daughter” cell must be an exact replica of its parent.  To make sure that that happens, DNA is capable of detecting and repairing any damage that might have occurred in a microscopic  process of remarkable complexity, mastered by living organisms eons ago.

These complex molecular structures are composed of intricate flotillas of atoms, atoms that have combined—by exchanging or sharing electrons—to form them.   Imagine, then, the consequences for living cells if their smallest subunits—atoms—lose their electronic stability (their balance of positive and negative electric charges).  They become ionized, or electrically charged ions; we know them as chemically unruly ‘free radicals.’  This can occur in a variety of ways, one of which is bombardment with very high frequency electromagnetic radiation (e.g., x-rays and gamma rays), which can break lose one or more electrons.[2]

The effects of ‘ionizing radiation’ can include the destruction of the molecules that form our DNA.  Certain proteins in our cells will enable those molecules to continue growing—but without the regulatory guidance of their finely constructed DNA.  This unregulated cell growth is what we call ‘cancer,’ named for the crab which it often resembles.

Radiation surrounds us and is as common to our lives as the night follows the day.  The sun’s radiance provides energy that turns into matter by powering natural and vital rearrangements of atoms’ electrons into different molecular combinations.  Among plants, for example, photosynthesis uses light energy from the sun to convert carbon dioxide and water into food, which is then consumed by animals—and ourselves.

Thus a certain amount of background or natural radiation is essential to life, and part of the DNA code that guides our cellular functions includes instructions for the repair of molecules damaged by ionizing radiation.  But at some point for each living organism the radiation it receives may exceed the native cellular repair capacity of its organs.  Just what that point is varies from individual to individual. Beyond a certain dose and duration of exposure, ionizing radiation is certain to overwhelm the orderly cell repair capacity of most people.

Medical x-rays represent a significant net increase to our cumulative radiation exposure over any given period of time.  In the 1970s, when annual mammography screening of asymptomatic women at low or normal risk for breast cancer began, medical x-ray exposure already “accounted for approximately 90 percent of . . . total radiation other than natural background [radiation].”[3]

X-rays effect different organs and tissues in different ways.  Variations in “probability and severity of harm” to living things from radiation are described by the International Atomic Energy Agency as “detriment,” which the IAEA calibrates by using a “tissue weighting factor” to determine the actual effective radiation dose for particular organs and tissues.  These tissue weighting factors (WT) range from 0.01 for skin and bone surface tissue, to 0.12 (or a multiple of 12) for bone marrow, breast, colon, lung and stomach tissue.[4]  Thus comparing x-radiation damage to breast tissue to general background radiation risk may understate the risk by as much as a factor of twelve.

Information about medical x-ray dosing in the case of mammography typically relies on ratings given by manufacturers of specific equipment used.  Such ratings assume a standard thickness of the compressed breast, a standard combination of glandular and adipose tissue (breast density), and standard x-ray beam characteristics.  In real life, however, the absorbed glandular dose (measured in Grays[5]) received during a mammogram can vary by nearly 50%, depending upon breast thickness and density.[6]  The newer three dimensional mammogram, or ‘breast tomosynthesis,’ which is similar to a CAT scan of the breast, involves yet more radiation.

Numbers are useful for calibrating machines, but when we discuss medical x-ray risk in terms of numers we imply that there is a number that represents relative safety, and that we know what that number is.  The numbers that represent radiation doses from mammography machines have little to do with our as yet imperfect understanding of the biology of cancer, which cannot be calibrated.  By relying such numbers—whatever the quantity of millisieverts we might agree upon—we are dissembling, pretending that we can adequately predict what will happen to an individual’s organs when struck by ionizing radiation, what results will follow, and most importantly, how and for how long those results will make a difference to the normal functioning of that person’s body.   But we cannot.

Long before the Health Insurance Plan (HIP) of Greater New York began its mammography trial in 1963,  scientists had demonstrated that carcinogenic capacity of ionizing radiation delivered as x-rays.   A major contribution to that research came from the German cytologist Theodor Heinrich Boveri’s studies of the chromosome in cell division and heredity.

In 1902 Boveri concluded from his work that there was a strong link between cancer and chromosomal abnormalities within the cell:

“The tumour problem is a cell problem . . .  The cells of even the most     malignant tumours can be formed from normal tissue cells.  . . . the differences between the cells of different tissues are ultimately determined by differences in the state of the chromosomes. . . . . The primordial tumorigenic cell . . . is a cell that harbours a specific faulty assembly of chromosomes as a consequence of an abnormal event. This is the main cause of the propensity for unrestrained proliferation that the primordial cell passes to its progeny . . . .”[7]

Boveri’s findings were first published in 1914 in his native German.  By 1929 his booklet was available in six English language editions both in the United States and Great Britain.  A half-century after the first appearance of Boveri’s essay on the chromosome and tumorigenesis, Science magazine in 1964 published an appreciation written by his fellow biologist and biographer, Fritz Baltzer.[8]

Meanwhile, the power of x-rays to infiltrate our bodies’ invisible depths has been known to us since Wilhelm Conrad Röntgen, experimenting with cathode ray (vacuum) tubes in 1895, discovered that electric current passing through a cathode ray tube could penetrate various materials and leave marks on photosensitive plates or film.  When such rays fail to penetrate, or are absorbed by, an intervening material such as the calcium in bone, they leave a white shadow on the dark background of a photosensitive surface.

Five years later, in 1901, Röntgen would receive the Nobel Prize in physics for a discovery which, by then, had—in today’s parlance—gone “viral.”  As medical imaging’s historian Bettyann Holzman Kevles describes it,

“Within weeks . . . X-ray Boy’s Clubs sprouted in the United States, and X-ray slot machines were installed in Chicago and Lawrence, Kansas, where, for a coin, you could examine the bones in your own hand. . . . Anybody could cobble together an X-ray machine, and just about anyone did. . . . There was no hint of danger.”[9]  It did not take long for the possible medical and industrial applications of X-ray machines to become apparent.  But danger, there was.

Initially, in the early 20th century, medical and dental exposures lasted for hours at a time, as patients, dentists, physicians, and x-ray tube makers all endured burns and deeper tissue damage, not to mention fatal metastatic carcinomas.  Thomas Edison famously abandoned work on x-ray tubes after his glassblower, Clarence Madison Dally, died in 1904, having suffered from what would later be called radiation sickness, and then finally losing both arms to cancer.[10]

Soon on the heels of Röntgen’s discovery, English physicist Joseph John Thomson, further investigating the properties of electricity as it passed through vacuum tubes, detected individual particles which were a thousand times smaller than atoms.  These he identified as subparticles of atoms, which he named electrons, produced when x-rays struck atoms with sufficient force to disperse one or more of their electrons, leaving behind unstable ions.

By the end of the 1920s biological investigations of genetic mutations had converged with research into the long-term damage from ionizing radiation.   Geneticist Hermann Joseph Muller, experimenting with varying doses of X-rays, discovered a directly proportional connection between radiation exposure and lethal genetic mutations in fruit flies.  His work, reported in 1926 at a scientific conference in Berlin, earned him the 1946 Nobel Prize in Physiology or Medicine.

Thus by World War II scientists had not only connected abnormal disruptions to the molecular structure of the chromosome and aberrant cell growth, but recognized that x-rays could produce those disruptions.  What had been previously only observed—a link between cumulative or prolonged x-ray exposures and cancer—was now understood.  All that remained was to determine the minimum extent of x-ray exposure that might produce oncogenes—or whether there was such a thing as a safe minimum exposure at all.

Within a few months after the U.S. atomic bombings of Hiroshima (August 6, 1945) and Nagasaki (August 9, 1945), Japanese and American scientists collaborated on the Atomic Bomb Casualty Commission to assess the radiation consequences of the bombings.  (Their work was continued, after 1975, by the Radiation Effects Research Foundation.)  Their efforts were handicapped by the difficulty of establishing the precise nature of the radiation emitted in any given location and relating those findings to other than broad-scale epidemiological data.   Added to that was the difficulty of determining the long-term effects of low-level ionizing radiation, because carcinomas can have long latency periods.  For decades after 1945 attributions of cancer cases to radiation from the bombings relied on estimates, and were regularly disputed.[11]

The National Academy of Sciences created in 1955 a committee on the biological effects of atomic radiation, with six subcommittees which investigated radiation’s effects on genetics, pathology, meteorology, oceanography and fisheries, agriculture and food supplies, and the disposal and dispersal of radioactive wastes.    The committee issued an initial assessment in 1956, which was updated for its 1960 report.[12]

The group examining genetic effects confirmed that irradiation of female mice produced genetic damage.  It also confirmed genetic consequences for the “children of survivors of the atomic bombings at Hiroshima and Nagasaki,” as well as “children elsewhere whose parents received radiation for medical or other reasons.”[13]

However, cautioned the report,  “. . . most of the man-made radiation to which the population of the United States is exposed involves dose rates not yet adequately investigated experimentally. For example, we do not know whether the effects of low doses given at high dose rates, as in medical exposures, will be more like the response from acute irradiation or more like that from chronic irradiation.”  Pathologies such as skin cancer and leukemia may result from “relatively low level” exposure “from time to time over a period of years. . . .” and it is “characteristic” of radiation that its “effects may manifest themselves not only immediately, but perhaps only after a long period of intermittent . . .exposure.

“Delayed manifestation of biological effects results from the fact that “all types of induced and spontaneous tumors appear not to arise at once . . . . There is much evidence indicating that malignant change ordinarily develops only after a series of ‘precancerous’ changes or a state of tissue disorder has taken place.”[14]

Given what the subcommittee on pathological effects had learned, and the questions remaining, it recommended against predicting “human tumor incidences from small radiation doses based on extrapolation from the observed incidences following high dosage,” such as those recorded after the atomic bombings of Japan.  Furthermore, prediction ” . . . requires evaluation of the possibility that there is a threshold dose below which there is no probability of inducing leukemia, a concept which implies a factor of safety that would be most reassuring to those who are exposed to radiation in excess of the natural background . . . .  However, no member of the Subcommittee feels that he can estimate the size of the threshold or, for that matter, even prove its existence. Accordingly, the Subcommittee believes it is prudent to assume that there is no threshold.” [15]

Subsequent reports from the National Academy of Sciences’ Committee to Assess Health Risks from Exposure to Low Level Ionizing Radiation have affirmed this conclusion.  For example, “. . . at the level of cancer-associated gene or chromosomal mutation, the presence of a true dose threshold demands totally error-free DNA damage response and repair.  The detailed information available . . . argues strongly against a DNA repair-mediated low-dose threshold for cancer initiation. [16]  James V. Neel, who served on the Academy’s subcommittee on genetic effects of atomic radiation, ensured that the entire medical profession could readily learn of its findings with his article in the February 22, 1958 issue of the Journal of the American Medical Association, titled “The Delayed Effects of Ionizing Radiation.”[17]                

And so, by 1960 the medical as well as scientific communities should have been fully aware that directing x-rays at any portion of the female body could violate the physician’s ethical duty to “do no harm.”  And yet women are still advised by generally trusted sources that screening mammography “is safe; there is only a very tiny amount of radiation exposure,” and “strict guidelines ensure that mammography equipment is safe and uses the lowest dose of radiation possible.” [18]

The National Cancer Institute has always been was somewhat less breezy on the subject, cautioning women to “always let their health care provider and the x-ray technician know if there is any possibility that they are pregnant, because radiation can harm a growing fetus.”[19]  Embedded in this caution is the recognition that it is not only the breast, but a woman’s entire torso, which is exposed (through x-ray scatter) to ionizing radiation.

Advances in all technological fields that contributed to allied victory in World War II included improvements in x-ray technology, first widely used in military hospitals during the previous world war.  By the 1960s breast compression, improvements in film, and the use of high milliamperage-low voltage x-ray technique had led to successful efforts at M.D. Anderson Cancer Hospital in Houston, TX to find possibly cancerous anomalies in the breasts of 1,000 women with no palpable symptoms.   Nearly all of the 245 ultimately confirmed breast cancers found during the experiment —including one that was as small as eight millimeter in diameter–had been detected by newly specialized mammography x-ray equipment.[20]

The availability of x-ray machines designed for breast imaging, along with the successful experiments at M.D. Anderson, inspired the hope that breast cancer deaths generally could be reduced as a result of x-ray screening for such small (“early”) cancers.[21]  Given the interventionist imperative of modern medicine, reinforced by a capitalist economy in which the conquest of disease is marketable, few questioned the necessity for further diagnostic mammography and biopsies for barely visible white (radiopaque) spots in the breast representing calcification–a sign of possible cell death. Fewer still doubted the need to treat all detected “early” cancers.  Few women were likely to appreciate that such irregularities do not in themselves represent cancerous growths.  Cancers are actually identified through diagnostic mammography and biopsies, which require additional and significantly more radiation exposure.

Only later would physicians begin to question the wisdom of attacking cancers that might otherwise never have caused symptoms or death in a woman’s lifetime, while subjecting women to surgical deformities, toxic radiation and chemotherapy.  Then there were the longer term risks— radiation induced lymphedema, new cancers, breast cancer metastasis, recurring breast cancers, and cardiac toxicity.[22]

All that was necessary at the end of the 1960s for the triumph of the new breast x-ray technology, not to mention its remunerative industrial and institutional infrastructure, was universal adoption of the policy, “early detection saved lives.”  That declaration came, without rigorous theoretical and experimental proof, from the Health Insurance Plan of Greater New York.

Meanwhile, the American Cancer Society in 1972, during the nation’s Cold War against the spread of communism, began its own national campaign to promote routine x-ray screening for breast cancer for all women, benefiting from the Nixon administration’s newly launched national “war on cancer.”  The ACS was ready to begin field testing its own version of a costly new weapon. Thousands upon thousands of trusting and unsuspecting women provided the proving grounds. š

(Published June 9, 2015.  Following posts will examine the risks to which women have been subjected as a result of the screening mammography experiment, and the unraveling of “mammography saves lives” as a medical protocol.)

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

[1] RNA or ribonucleic acid, also resident in the human chromosome, has more varied structures thanks to its principal roles, which are to convey DNA instructions to proteins and to assist in the transfer of DNA during cell division.

[2] Higher frequency ultraviolet radiation begins to have enough energy to break chemical bonds. X-ray and gamma ray radiation, which are at the upper end of magnetic radiation, have very high frequency in the range of 100 billion Hertz and very short wavelengths 1 millionth of a meter. Radiation in this range has extremely high energy, enough to strip off electrons or to break up the nucleus of atoms.  See: “Ionizing & Non-Ionizing Radiation,” Environmental Protection Agency, http://www.epa.gov/radiation/understand/ionize_nonionize.html.  Downloaded November 13, 2014.

[3] J. Samuel Walker, Permissible Dose:  A History of Radiation Protection in the Twentieth Century (University of California Press,  2000), p. 80.

[4] International Atomic Energy Agency, Training Material on Radiation Protection in Diagnostic and Interventional Radiology, “Radiation Units and Dose Quantities.” https://rpop.iaea.org./ Downloaded March 3, 2014. [Slide 26].

[5] A gray is a measure of the radiation energy absorbed per a unit of mass. One ‘gray’ = one joule of radiation energy by one kilogram of matter.

[6] V. Patel et al, “Patient Specific Average Glandular Dose in Mammography,” Paper presented at the 55th Annual Meeting of the American Association of Physicists in Medicine, August 4-8, 2013, Indianapolis, Indiana.

[7]  Theodor Boveri, “Concerning the Origin of Malignant Tumours,” Translated and annotated by Henry Harris, Journal of Cell Science (January 1, 2008).  Originally published as Zur Frage der Entstehung maligner Tumoren (Jena, 1914), trans. by Marcella Boveri as The Origin of Malignant Tumors (Baltimore, 1929).

[8] OCLC WorldCat.  “All Editions for ‘The Origin of Malignant Tumors.”  Fritz Baltzer, “Theodor Boveri,” Science, Vol. 144 (15 May 1964), pp. 809-815. See also Samantha Hansford and David G Huntsman, “Boveri at 100: Theodor Boveri and Genetic Predisposition to Cancer,” The Journal of Pathology, Vol. 234 (October 2014), pp. 142-145.

[9] Bettyann Holtzmann Kevles, Naked to The Bone: Medical Imaging in The Twentieth Century  (Rutgers University Press, 1997). Kindle edition, location 390.

[10] Bettyann Holtzmann Kevles, Naked to The Bone: Medical Imaging in The Twentieth Century  (Rutgers University Press, 1997), Chapter 2.  See also K. Sansare, V. Khanna, and F. Karjodkar, “Early Victims of X-rays: A Tribute and Current Perception,” DMFR: Journal of Head & Neck Imaging (February, 2011), pp. 123-125, and Percy Brown, M.D., American Martyrs to Science  through the Roentgen Rays (Springfield, Ill.: Charles C. Thomas, 1936).

[11] For an account of these post-Hiroshima investigations and the resulting disputes see J. Samuel Walker, Permissible Dose: A History of Radiation Protection in the Twentieth Century (University of California Press, 2000), especially Chapter 5.  Also: M.  Susan Lindee, Suffering Made Real: American Science and the Survivors at Hiroshima (University of Chicago Press, 1994), William J. Schull, Effects of Atomic Radiation: A Half-Century of Studies from Hiroshima and Nagasaki (New York: Wiley-Liss, 1005), and U.S. General Accounting Office, Problems in Assessing the Cancer Risks of Low-Level Ionizing Radiation Exposure (EMD-81-1) January 2, 198l.

[12] National Academy of Sciences-National Research Council, The Biological Effects of Radiation:  Summary Reports (Washington, DC: 1960).

[13] National Academy of Sciences-National Research Council, The Biological Effects of Radiation:  Summary Reports (Washington, DC: 1960), p. 3.

[14] National Academy of Sciences-National Research Council, The Biological Effects of Radiation:  Summary Reports (Washington, DC: 1960), pp. 27-29.

[15] National Academy of Sciences-National Research Council, The Biological Effects of Radiation:  Summary Reports (Washington, DC: 1960), pp. 32-35.

[16] National Academy of Sciences, Biological Effects of Ionizing Radiation, V (National Research Council, 1990),  National Academy of Sciences, Biological Effects of Ionizing Radiation, VII, Phase 2 (National Research Council,  2006), p.245.

[17] James V. Neel, M.D., Ph.D., “The Delayed Effects of Ionizing Radiation,” Journal of the American Medical Association, Vol. 166 (February 22, 1958), p. 908.

[18] “Mammography: Benefits, Risks, What You Need to Know,” www.breastcancer.org, downloaded March 20, 2014;

[19] “Mammograms Fact Sheet,” National Cancer Institute, http://www.cancer.gov, downloaded February 19, 2015.

[20] Barron H. Lerner, “’To See Today with the Eyes of Tomorrow’: A History of Screening Mammography,” Canadian Bulletin of Medical History, Vol. 20:2 (2003), pp. 300-302.  Radiographic image quality is a function of kilovoltage, amperage, and time of exposure.

[21] For a more recent critique of the limits of ever advancing breast imaging technology, see C.W. Stevens and E. Glatstein, “Beware the Medical-Industrial Comples,” Oncologist Vol. 1 (1996). http://www.nvbi.nlm.nih.gov/pubmed/10388005. Downloaded January 5, 2015.

[22]National Cancer Institute, “Brest Cancer Institute: Harms of Screening Mammography,” updated February 6, 2015. http://www.cancer.gov/cancertopics/pdq/screening/breast/healthprofessional/page8.  Downloaded February 21, 2015).

Post to Twitter Tweet This Post

Posted on: 05.26.2015

Mammography’s Shadows, III: The Campaign

by Sylvia Kraemer
No Comments »

Tags: , , , , , , , ,


Posted in Healthcare, Science and Policy

Crab ImageScientists at the National Cancer Institute recognized the limitations of the mammography screening trial conducted during 1963-1969 by the Health Insurance Plan of Greater New York (HIP-GNY).  Those limits prevented the trial from supporting a widespread screening protocol for breast cancer among asymptomatic women of average risk. (See previous post, “Mammography’s Shadows, II:  Numbers and the First Large X-Ray Screening Trial.)  But their concerns were overridden by media inflated fears of breast cancer, and the organizations whose members stood to gain from widespread breast cancer screening.

For the careers and institutions committed to the understanding, diagnosis, and treatment of cancer, 1971 was an annus mirabilis.   That year the Journal of the American Medical Association published a report of the HIP-GNY breast cancer screening study that purportedly proved that early detection with mammography screening “saves lives.”

It was also the year that Congress passed, and President Richard Nixon signed, the National Cancer Act of 1971, which had strong bi-partisan support.   Provisions in the legislation ensured that the NCI, established in 1937, would become a virtually autonomous unit of the National Institutes of Health (NIH),  First, the NCI director would be appointed by the president. Then the institute would be able to submit its own budget to the White House, and have its own independent procurement authority, which meant that it could award grants and contracts without NIH review.  These provisions signaled the success of a masterful maneuver for those who lobbied aggressively for the legislation, among them, the American Cancer Society (ACS).

The influence the American Cancer Society could wield over the National Cancer Institute was foretold by President Nixon himself, who nominally originated the legislation with a message to congress earlier in 1971.  During the bill’s White House signing ceremony Nixon invited to the dais only two (non-congressional) dignitaries:  chair of the President’s Cancer Panel Benno Schmidt, a lawyer and wealthy partner in the New York investment firm J.H. Whitney & Co., and Dr. Alva H. Letton, physician and president of the American Cancer Society.  Each man received one of the two pens Nixon used to sign the act.  Nixon invited Letton to speak, which he did, briefly, commending the new War on Cancer as “the greatest thing ever done by the United States.”[1]

Shortly thereafter the American Cancer Society planned its own campaign in the War on Cancer.  The campaign had two leading salients–a national membership campaign, and a marketing campaign for routine screening mammography.  The mammography

screening campaign would be named the national Breast Cancer Detection Demonstration Project (BCDDP), thereby implying that the detection method being used had been proven to be both safe and effective at defeating breast cancer.

Since its lobbying had resulted in a substantial increase in the NCI’s budget, the American Cancer Society turned to the NCI for funding for its project to recruit over a quarter-million women for annual screening mammography.  The society’s objective was to “search out people who have undetected cancer” by convincing the public that “early detection saves lives.”[2]  Like all large screening programs, the campaign would increase revenue streams not only for physicians and clinics, but for x-ray equipment manufacturers and pharmaceutical companies. [3]

The National Cancer Institute’s own civil service scientists undoubtedly knew at the time that the carcinogenic effects of x-rays had been demonstrated before World War II, and confirmed thereafter by the National Academy of Sciences’ panels on the biological effects of exposure to ionizing radiation.   Moreover, the probability that physical compression of, and piercing or cutting into, breast tumor cells might cause metastasis, could have been readily suspected.  In any event, physicians had been warned of that possibility as early as 1958.[4]  Questioning the validity of the HIP-GNY study, which was cited as having proven the value of screening mammography, scientists at the National Cancer Institute opposed NCI support of the American Cancer Society’s screening mammography campaign.

Most vocal among them was NCI’s John C. Bailar, III, a noted epidemiologist who had also trained in medicine at the Yale University of Medicine before turning to statistics.  As NCI’s deputy associate director for cancer control he reviewed the ACS’s proposed program. Bailar was soon troubled not only by the seemingly indiscriminate exposure to x-radiation of thousands of asymptomatic women, but by the fact that there were no controls to ensure consistent compliance with standard mammography procedures or dosages among the 27 screening centers involved.[5]

His concerns were dismissed at NCI by the explanation that the project’s “objectives have been pretty well dictated by the American Cancer Society.  In summary they are ‘Can American Cancer Society volunteers mobilize a large number (100,000 per year) of volunteers for thermography, mammography, and a physical exam?’”[6]

Civil-service scientists do not typically question work sponsored by their own organizations, so one must suspect that Bailar had considerable support from his peers when he submitted a manuscript to the Annals of Internal Medicine in June of 1975 in which he “regretfully” concluded “that there seems to be a possibility that the routine use of mammography in screening asymptomatic women may eventually take almost as many lives as it saves.”  Using ionizing radiation risk estimates developed by the National Academy of Sciences, he cautioned that mammography doses could substantially increase not only the incidence of breast cancer, but “lesser hazards of radiation induction of leukemia, lung cancer, or other conditions.”[7]

Bailar noted that the methodological deficiencies in the HIP-GNY study (e.g., self-selection by participants and lack of clarity about the clinical breast exam techniques used for both study and control groups) rendered useful interpretation of its numbers difficult.  Perhaps the greatest pitfall of attempting to quantify in years survival as a result of mammography, Bailar pointed out, was reflected in two biases evident in the HIP study:  “lead time” and “length time.”  The lead time bias invites the mistaken view that a cancer detected through mammography three years before it would have been detected clinically or through breast self-exam results in the addition of three years’ life—“survival”–to the patient’s prognosis.

The length-time bias results when an asymptomatic and indolent neoplasm, which would likely result in a good prognosis, is detected through mammography and survival is attributed to mammography.[8]  In short, given the complexities of cancer such as wide variations in latency and aggressiveness, attempting to quantify the relationship of early detection to mortality would produce debatable conclusions at best.

Bailar was not alone in his misgivings about a project that would be largely funded by the NCI.[9]  Scientists at the Institute voiced concerns not only about the lack of standardization in x-ray equipment, but “the possible hazards of ionizing radiation and the ability of an uncontrolled study to generate any meaningful conclusions about the value of screening mammography.”[10]  Other statisticians agreed, also noting “the absence of a control group” which would prevent one from comparing results from the BCDDP with “data derivable from other sources.”

One leading radiation scientist questioned whether “mass screenings involving mammograhy is consistent with good radiation protection theory.”[11]   Roswell Park Memorial Institute (cancer research center) biostatistician Irwin D. J. Bross warned, “many more cancers are produced than cured by x-rays …. This exposure to diagnostic x-ray will probably result in the worst iatrogenic epidemic of breast cancer in history.”[12]

In spite of the NCI scientists’ concerns, director Frank J. Rauscher, Jr. approved the joint project.  Rauscher, who had been a scientist at the NCI since 1959, was appointed to the post by the ACS’s friend Richard Nixon, undoubtedly with the organization’s approval, if not at its suggestion.  He was rewarded in 1976 for his support for the ACS project with a new position as Vice-President for Research at the ACS, at nearly double the salary he had been receiving at the NCI.[13]   His new boss at the ACS, R. Lee Clark (Byrd’s successor), had previously served on the President’s Cancer Panel and president of the Cancer Center at the M.D. Anderson Hospital and Tumor Institute,[14] where some of the earliest uses of mammography had occurred.  That institution would be one of the recipients of NCI funds to participate in the BCDDP.

By October 1975 the NCI was under assault for supporting the project.   To respond to its critics the NCI created three expert panels to review the efficacy and safety of screening mammography.  Having reviewed the HIP-GNY study, which the ACS asserted validated the “benefit” of mammography screening through a random controlled trial, the NCI panels’ report concluded that half of the cancers claimed to have been found only by mammography in the HIP study were, in fact, “palpable, in no sense clinically occult.”  Proper review of any uncertain physical exam results might have prevented the resort to mammography at all in those cases.  At the same time, “mammography was negative” for over 40% of the cancers detected through clinical breast exam. [15]

The institute’s review panels’ report, issued in March of 1976, should have brought the project to a halt.  The report concluded that it was “difficult to assess the independent contribution of mammography” to any benefit of screening for women over 50 [italics added].   But rather than suggest that screening be stopped, the report temporized by recommending that “x-ray dosages should be kept as low as possible.”  As for mammography for younger women, NCI support for such screening should “be concentrated on validating its use through appropriately designed randomized trials.”[16]

The Breast Cancer Detection Demonstration Project was completed in 1981.  During that period controversy over the program continued unabated, so the National Institutes of Health, parent department to the NCI, did what many institutions do when faced with serious controversy:  It sought to achieve a negotiated resolution of the issues—relying on process to obtain an outcome that a majority would accept. In 1977 the NIH convened the first of several “consensus conferences” held during the next two decades on the merits of mammography.  Conference topics in 1977 included reviews of pathology specimens from biopsies conducted as a result of BCDDP screening.

One such review found that 66 of 506 pathological specimens taken thus far in the program “contained neither cancer nor carcinoma in situ.” As a result, 58 of the women from whom those specimens had been taken suffered unnecessary mastectomies.[17]  Rather than regard these grievous errors as a serious risk of screening mammography, NCI declined to halt the program and referred the matter to those who made the diagnoses and performed the surgeries.  As for whether to inform the misdiagnosed women of the mistaken results, the NCI side-stepped that moral obligation by leaving notification up to the women’s own physicians.[18]

When women recruited for the BCDDP were asked the source of their information about the campaign, their answers must have pleased the ACS, for which the project had always been essentially a marketing campaign.  Slightly over 90% had heard about it through social contacts, the media, or ACS volunteers.[19]  But what that number also revealed was that less than 10% had been recruited by their physicians on the basis of individual medical assessment.  Thus over 90% of the BCDDP’s research subjects were self-selected for what most likely was a combination of personal reasons, social persuasion, and American Cancer Society assurances that they would benefit.

Slightly over a quarter of a million women participated in the Breast Cancer Detection Demonstration Project, or only .67% of the entire population in the country of women between the ages of 35 and 74. (In 1970 there were 40.4 million women resident in the United States in that age group.)  Since there is no way we could consider the participants in the BCDDP as representative of that larger population, using data from the project as a basis for establishing health policy or medical screening protocols was scientifically unsupportable.  Given the risks these women were subjected to, risks of which they knew little if anything, it was also ethically reprehensible.

Never adequately examined have been the consequences for these women of the radiation exposures they received during their five annual screenings. In the fall of 1976, not long after the NCI’s review panels issued their report, the Health Research Group of Public Citizen called for stronger informed consent requirements for “women undergoing mammographies at … federally sponsored screening centers across the country.”

In its letter to Dr. Theodore Cooper, assistant secretary at the department of Health, Education and Welfare which oversees the National Institutes of Health, the group cited “mammography machines which are emitting enough excessive radiation so that the absorbed dose is more than one rad per exam, a danger even to women over 50.” [20]  (The NCI’s own BCDDP review panels had found “substantially higher [radiation] exposure levels in unmonitored screening clinics.”[21])

While supporters of mammography screening relied exclusively on unreliable quantitative data in an effort to prove its benefits, quantitative data became magically unimportant when considering its risks.   Responding to the Health Research Group’s warnings about excessive radiation exposure, a National Cancer Institute official declared “’that’s uncertain.  There just isn’t enough information to quantify the risk that much.”[22]

Women who entered the program at ages 35-44 had nearly twice as many instances of new breast cancers detected between the first and fifth year of screening as did women who began five years of screening at age 45 and older (which does not support claims that older women are at greater risk of breast cancer than younger women, and thus can benefit from mammography screening).  At the same time, women between the age of 40 and 45 participating in the BCDDP experienced double the number of new cancers detected in the fifth year as were detected in their first year.[23]

Thus the longer women remained in the program, the more likely they were to have new breast cancer detected in the fifth year of their participation.[24]  The possibility that a higher detection rate in the fifth year might be attributable to cumulative x-ray exposure during the previous four years was not mentioned in the BCDDP five-year summary report.

As with virtually all attempts to justify screening mammography by linking it to breast cancer mortality data, BCDDP-reliant articles in medical literature sampled from the 1980s and 1990s overlooked the important role of breast cancer treatment on survival rates.  Disregarding treatment as a critical variable in cancer mortality assumes that the same treatment was provided to all of the women diagnosed with cancer at the same age and stage in their cancers, and that all women responded to that same treatment uniformly.  Such assumptions are clearly untenable.

In any event, in 1997 the National Institutes of Health convened a 12-member panel for a ‘Consensus Development Conference’ with an audience of 1,100 in hopes of resolving the question of whether women in their 40’s should undergo routine screening mammography.  The panel concluded that “the data currently available do not warrant a universal recommendation for mammography for all women in their forties.” That decision belonged to individual women, deciding for themselves, with “access to the best possible relevant information regarding both benefits and risks.”

Such decisions would be “difficult,” because they involved not only “scientific evidence and . . . her individual medical history;” they also involved each woman’s perception of “each potential risk and benefit, the values she places on each, and how she deals with uncertainty.”  Finally, “a woman’s health care provider must be equipped with sufficient information to facilitate her decision making process.”  Unfortunately, information then available to women and their health care providers was inadequate to warrant annual x-ray breast cancer screening for asymptomatic women of average or low risk.

Women over the age of 50 have occupied a curious category in the ongoing effort to market screening mammography for healthy women at normal risk for breast cancer.  Both proponents and a few critics of adopting the practice as a standard medical protocol opined that the women most in danger of x-ray harm were women under 50, while women over 50 had been shown to “benefit.”   Since the problems with the HIP-GNY study applied to the entire study, it could not be said to support mammography screening for older women any more than younger women.  Nor did the BCDDP demonstrate such a benefit.

Was it that older women were more prone to breast cancer?  If so, they did not become more prone to it until after the inception of mammography screening.  Cancer deaths among women over 45 as well as women over 55 declined steadily during the 1950s and 1960s, only to rise after 1970.  Since a majority of breast cancers are estrogen hormone responsive, it would seem natural that post-menopausal women would be less likely to develop breast cancer.  But after three decades of routine mammography screening, the cancer death rate for women over 45 and 55 (as for all women) in 2000 exceeded the rate in 1950.[25]

Absent compelling epidemiological or laboratory evidence that all women over the age of 45 or 50 are more prone to breast cancer, that age threshold begs other explanations.  Was it that older women could be exposed to x-radiation with less concern about its consequences because their instrumental value was diminished, i.e., they were less likely to get pregnant, or to be nursing, or to have the care of young children?  Was it that if they were, indeed, to get x-ray induced cancer, it would not appear until their late 50s or later, at which time they might be just as likely to die of other causes as well as breast cancer?

Detecting and treating breast cancer at any stage was and remains far more profitable for the medical-industrial complex[26] than is cancer prevention.  It is women–not those who gain materially from their treatment–who endure debilitating chemotherapy and radiation therapy, unnatural hair loss, mutilating surgeries, and catastrophic expense for those who are inadequately insured.

A cavalier disregard for this aspect of ‘curing’ breast cancer is reflected in ACS President (in 1976) Dr. Benjamin F. Byrd, Jr.’s response, when queried about the cancer risk of x-ray screening.  “Even if there is a slightly increased risk of her getting the disease in the distant future, there’s also an excellent chance that by that time science will have learned to control the disease.”[27]

In all probability the 45 or 50 year threshold for routine screening mammography appealed because it offered a compromise in a highly contested medical protocol.  Screening mammography’s opponents could ‘hold the line’ for younger women, at least, who supposedly had more to lose from the ravages of breast cancer than older women.  As a compromise, the 50 year threshold enabled physicians to go about their business without being stymied by the dispute.  Meanwhile, millions of asymptomatic women, urged on by powerful and trusted organizations (and sometimes their own physicians) to get their yearly screening mammograms, conscientiously complied.

(Published May 26, 2015.  The next post examines the radiation risk of low-dose x-ray mammography, noting that those risks were known well before the American Cancer Society’s 1970s campaign to market screening mammography.)

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

[1] “Nixon Signing the National Cancer Act of 1971,” National Cancer Institute, News and Public Affairs.  Video uploaded November 8, 2009 to You Tube.  See https://www.youtube.com/watch?v=E2dzEDnGqHY.

[2] Lane E. Adams, “Executive Vice President’s Report,” American Cancer Society Annual Report, 1977. http://tobaccodocuments.org/rjr/502379608-9644.html. Downloaded December 29, 2014.

[3] For example:  “Guttman Institute Reopens with Expanded Screening Services,” Cancer Network (Sept.01, 1996).

[4] J. W. Hendrick, M.D., Results of Treatment of Carcinoma of the Breast, Five to 18 Years,” Annals of Surgery, Vol. 146, pp. 728-750 (November 1957); J.W. Hendrick, M.D., “Aspiration Biopsy in Breast Cancer,” Journal of the American Medical Association, Vol. 166, No. 8 (February 22, 1958), p. 892.

[5] Daniel S. Greenberg and Judith E. Randal, “The Questionable Breast X-ray Program,” Washington Post (May 1, 1977).

[6] Daniel S. Greenberg and Judith E. Randal, “The Questionable Breast X-ray Program,” Washington Post (May 1, 1977).

[7] John C. Bailar, III, “Mammography: A Contrary View,” Annals of Internal Medicine, Vol. 84 (1976), pp. 80-82.

[8] John C. Bailar, III, “Mammography: A Contrary View,” Annals of Internal Medicine, Vol. 84 (1976), pp. 77.

[9] Daniel S. Greenberg and Judith E. Randall, “The Questionable Breast X-ray Program,” Washington Post (May 1, 1977).

[10] Barron H. Lerner, M.D., The Breast Cancer Wars: Fear, Hope, and the Pursuit of a Cure in Twentieth-Century America (Oxford University Press, 2001), Kindle edition, location 213.

[11] Barron H. Lerner, M.D., The Breast Cancer Wars: Fear, Hope, and the Pursuit of a Cure in Twentieth-Century America (Oxford University Press, 2001), Kindle edition, location 212-213.

[12] Daniel S. Greenberg and Judith E. Randal, “The Questionable Breast X-Ray Program,”  and “Waging the Wrong War on Cancer,” The Washington Post (May 1, 1977).

[13] Daniel S. Greenberg, “X-Ray Mammography: Silent Treatment for a Troublesome Report,” New England Journal of Medicine, Vol. 296, No. 17 (April 28, 1977), p. 1015.

[14] Daniel S. Greenberg, “X-Ray Mammography: Silent Treatment for a Troublesome Report,” New England Journal of Medicine, Vol. 296, No. 17 (April 28, 1977), p. 1015.

[15] Daniel S. Greenberg, “X-Ray Mammography: Silent Treatment for a Troublesome Report,” New England Journal of Medicine, Vol. 296, No. 17 (April 28, 1977), p. 1016.

[16] Daniel S. Greenberg, “X-Ray Mammography: Silent Treatment for a Troublesome Report,” New England Journal of Medicine, Vol. 296, No. 17 (April 28, 1977), p. 1016.

[17] Barron H. Lerner, “To See Today With the Eyes of Tomorrow: A History of Screening Mammography.” Canadian Bulletin of Medical History, Vol. 20, No. 2 (2003), p. 311; Daniel S. Greenberg, “A Cancer Controversy:  Did Doctor Know Best?” The Washington Post, April 4, 1978, p. A19.

[18] Barron H. Lerner, “To See Today With the Eyes of Tomorrow: A History of Screening Mammography.” Canadian Bulletin of Medical History, Vol. 20, No. 2 (2003), p. 311-12; “From the Editor,” New York Times, October 8, 1977.

[19]   Based on 10% sample of initial patient history records. Larry H.  Baker, M.D., “Breast Cancer Detection Demonstration Project: Five-Year Summary Report,” CA-Cancer Journal for Clinicians, Vol. 32, No. 4 (July/August, 1982), pp. 195-196.

[20] “Mammography Risky, Ralph Nader Warns,” The Milwaukee Sentinel, (November 3, 1976), p. 4.

[21] Daniel S. Greenberg, “X-Ray Mammography: Silent Treatment for a Troublesome Report,” New England Journal of Medicine, Vol. 296, No. 17 (April 28, 1977), p. 1016.

[22]  “Mammography Risky, Ralph Nader Warns,” The Milwaukee Sentinel, (November 3, 1976), p. 4.

[23] Larry H.  Baker, M.D., “Breast Cancer Detection Demonstration Project: Five-Year Summary Report,” CA-Cancer Journal for Clinicians, Vol. 32, No. 4 (July/August, 1982), p. 208.

[24] Larry H.  Baker, M.D., “Breast Cancer Detection Demonstration Project: Five-Year Summary Report,” CA-Cancer Journal for Clinicians, Vol. 32, No. 4 (July/August, 1982), p. 208.

[25] Source: Centers for Disease Control, National Center for Health Statistics, Health, United States, 2013: With Special Feature on Prescription Drugs, Hyattsville, MD (2014); Centers for Disease Control, National Center for Health Statistics, Health, United States, 2010: With Special Feature on

Death and Dying, Hyattsville, MD (2011).

[26] Stevens, CW, Glatstein, E, “Beware the Medical-Industrial Complex,” Oncologist,Vol.1,No.4(1996), http://www.ncbi.nlm.nih.gov/pubmed/10388005.

[27] Daniel S. Greenberg and Judith E. Randal, “Waging the Wrong War on Cancer,” The Washington Post, (May 1, 1977).

Post to Twitter Tweet This Post