THE NATIONAL Cancer Institute provided funds for one of the greatest ventures in mass screening for disease - the Breast Cancer Detection Demonstration Project, conceived by the American Cancer Society and conducted at 27 medical centers throughout the country. More than 80 per cent of the total cost of at least $54.6 million was paid by NCI.
The program is worth looking at in detail, for it illustrates the tail-dog relationship that exists between the relatively small but powerful ACS and the timid but affluent giant that is supposed to be in charge of the government's campaign against cancer, the National Cancer Institute.
For both health and aesthetic reasons, breast canser is a fearsome disease of women. Currently, some 90,000 new cases are diagnosed each year; the disease now causes some 33,000 deaths a year. It is said by the ACS to be the leading cause of death among women ages 40-44, though that often-used statistic is true only if one divides fatalities from heart disease into sub-categories.
The risks of getting the disease are linked to various criteria: A family history of breast cancer carries with it an increased likelihood of affliction; susceptibility also increases over age 50; women over 30 who have not had children are more prone than those who have given birth, and there is some evidence that the onset of menstruation prior to age 12 increases the risk.
It is a combination of factors that must be considered and it is not yet possible to weigh the various risks accurlately.
Left untreated, invasive breast cancer is almost always fatal, since the disease spreads to other parts of the body. Success rates in treatment are closely related to the stage of development. Therefore, great efforts have gone into devision detection techniques. The most common of these are physical examination for suspicious lumps - a harmless and highly effective procedure for detecting the disease after the tumor reaches a sufficient size - and X-rays, a possible risky though often effective technique for detection before breast cancer is otherwise evident.
X-rays, however, like other diagnostic methods, are not infallible; studies show they miss many cancers that are detectable by simple physical examination. X-rays are also dangerous and perverse. They are a potent source of cancer, since they promote biological changes that can blossom into malignacy a decade or more later, depending on the dosage. At low dosages, the risk is low; nonetheless, no dose is so low that it can be considered absolutely safe. Thishas been established by a variety of studies, among them careful follow-ups of persons exposed to varying degrees of radiation in the atomic bomb attacks on Japan. Thus, prudent radiologists hold that any exposure must be justified in terms of the potential benefits outweighing the possible risks.
There are also other problems of X-rays. Since the density of breast tissue declines with increasing age, X-rays can "see" more in older women, particularly in those over 50. Significantly, this is the age at which the incidence of the disease tends to rise. In younger women, not only are X-rays less revealing, but they are also more likely to trigger cancer eventually, making them most risky for those who have the longest to live.
Studies of persons who were inadvertently exposed to radiation, or who had received radiation in the course of ill-conceived medical treatments years ago, show that teenagers and young adults are especially susceptible in the long run to X-ray-induced cancer.
There is a third method of breast-cancer detection, thermography, which senses differences in the body's heat radiation patterns to locate suspicious tissues. Unlike X-rays, it is non-intrusive and harmless, but the technique requires further refinement to be reliable.
WITH THIS BACKGROUND in mind, let's look at the origins of the NCI breast cancer screening program.
The genesis of the program was in 1963, when New York's Health Insurance Plan (HIP), one of the leading comprehensive health care plans in the nation, began a study to determine whether periodic screening would reduce the number of deaths from breast cancer.
Some 62,000 women, ages 40-64, were divided into two groups. Half were offered annual physical and X-ray examinations for breast cancer, of whom about 20,000 accepted, and half continued with their usual health care habits. Nine years later, 98 deaths attributed to breast cancer had been reported among those who had received the regular examinations; there were 128 deaths in the control group. On the face of it, periodic screening, including X-rays, had produced a significant increase in lives saved by early detection of the disease.
When the returns first came in, they were received as a major finding. Upon passage of the National Cancer Act of 1971, the ACS Board of Director adopted a resolution calling for a nationwide "demonstration" project aimed at applying the HIP experience on a far broader scale.
The idea was to demonstrate the value of periodic screening so that the both the public and the medical profession would become acquainted with it and adopt it as a standard part of health care.As the plan evolved, it called for designating 20 - later raised to 27 - screening centers around the country at which 280,000 women would be given annual physical, X-ray and thermography examinations for five years. There would be no control group for comparative purposes, since the HIP study was taken as evidence that screening paid off. The object was to evangelize the HIP experience rather than to test it.
The minimum age for participation was set at 35, though it was evident from even early analysis of the HIP findings that the hazards of X-raying women under 50 were not outweighed by the benefits. Records of NCI-ACS planning sessions show that the age issue was raised, but it had no effect on the decision to begin with age 35. Minutes of a meeting held Jan. 9, 1974, report Dr. Philip Strax, president of the Guttman Institute of New York, as remarking "that mammography was of virtually no value in women under 50 years of age." The statement, backed up by the HIP findings, was noted but not heeded.
There were other objections, too. As the program was being formulated, the ACS design for mass screening was reviewed by Dr. John C. Bailar III, who was then NCI's deputy associate director for cancer control.
Bailar, physician-statistician, was troubled by the absence of experimental controls - comparative groups that might yield sophisticated data about the value of screening. His concerns were intensified by the fact that the 27 screening centers were not required to conform to standardized procedures; each was free to conduct the screening in its own way.
In reply to an inquiry from Bailar, Dr. Kenneth B. Olson, chief of the diagnosis branch in NCI's division of cancer biology, wrote a memo, which said in part:
"This project has limited objectives and they 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? . . . Why try to write research or controls in this ongoing program?'"
ACS was calling the signals on this government-financed program. NCI was even told how its own funds for the screening centers were to be allocated geographically.
According to minutes of a 1973 meeting with NCI officials, "ACS was firm in its requirement that the demonstration projects should be distributed equally among the four ACS geographical areas." On top of that, ACS stipulated that the medical institutions serving as screening centers must not solicit public contributions during ACS' traditional spring fund-raising drive.
SINCE NO ONE involved intended to do harm, the question arises as to the motivations for putting into operation an ill-designed and even dangerous program. As Irwin D. J. Bross, director of biostatistics at Roswell Park Memorial Institute, pointed out last year, "Extensive information about the hazards of ionizing radiation used in the mammography of symptom-free women under 50 was available in the early planning stages of the program." Citing various American British and Canadian studies, Bross charged that "all evidence was available," but he cited an ACS statistician as saying that "no one at ACS appears to have looked carefully at these hazards and realized their seriousness" - which was that in symptom-free women under 50, "many more cancers are produced than are cure" by X-rays.
The most probable reasons for steamrollering on are to be found in as assortment of factors, among them:
ACS's traditional desire to reach the public, a goal which has both therapeutic and fund-raising elements to it. The 280,000 women in the screening program would serve as a word-of-mouth force that would spread news of breast screening, and ACS's role in it, to many times that number. ACS has long thrived on promoting "checkups and checks."
Enthusiasm on the part of radiologists, of whom Bross later warned: "When enthusiasts for a technology are making decisions on the use of this technology, it is almost impossible to be 'forceful enough' to transmit a message about hazards that they do not want to hear."
Bailar later referred to the X-ray proponents as "gungho mammographers," and Dr. William Pomerance, chief of the diagnostic branch of the NCI Divison of Cancer Biology and Diagnosis, subsequently wrote to a colleague about a meeting with "some contractors in breast cancer management" at which he expressed concern about X-raying women under age 50. "They all 'fell on me,' "he reported" . . . and even went of far as to decide in their protocol that they would start with age 30."
Finally, the program gained momentum from excitement over the public relations yield that would be had from drawing substantial numbers of women into the War on Cancer. As Dr. Nathaniel I. Berlin, then director of NCI's Division of Cancer Biology and Diagnosis, told a planning session in the early days of the program, according to minutes of the meeting, ". . . both the ACS and the NCI will gain a great deal of favorable publicity because they are bringing 'research findings to the public and applying them.' This will assist in obtaining more research funds for basic and clinical research which is sorely needed."
AS THOUSANDS of women joined the screening program, an assortment of problems developed. Bross and others critics charged that the program was being conducted in violation of regulations that require informed consent from experimental subjects.
NCI replied that the program was a "demonstration," not a research, project, and therefore was not affected by informed-consent requirements - a proposition of dubious legal validity. Nevertheless, minimal forms were adopted and later, under a barrage of criticism, were revised to include warnings of radiation hazard.
More serious, however, was evidence that many of the X-ray machines at the 27 centers were poorly calibrated and were applying radiation far in excess of what was safe or necessary for obtaining useful pictures. Through a freedom of information request, Ralph Nader's Health Research Group obtained data on 57 X-ray machines used in the program and found that 17 were producing radiation levels that were ominously high, including one at Georgetown University that was delivering three times the recommended maximum dosage.
The Cancer Institute has since reported that these shortcomings have been corrected. Monitoring of the overexposed women, however, poses a serious difficulty, since many of the screening centers have neglected to keep careful records for follow-up purposes.
Last August, after doubts about the program began to become public - mainly because of a one-man barnstorming campaign by Bailar - the NCI and ACS jointly issued "interim guidelines" terminating routine X-ray screening of women without symptoms under 50.
Almost immediately, however, ACS began a public relations program that ranged from medical advice columns in womens's magazines to an interview with its past president, Dr. Benjamin F. Byrd Jr., in the Reader's Digest. The main point made in the ACS campaign was that, if a woman is a "high risk," she should be routinely X-rayed, no matter what her age and what the dangers might be.
Perhaps the hardest-hitting part of the pro-mammography counterattack was in an "urgent message," widely distributed to doctors and hospitals, as well as the public, by the New York City division of ACS and identified as a document that "reflects opinions shared by breast cancer authorities."
Listing the usual criteria of high risk - such as family history of breast cancer or suspicious lumps - the New York City division added that a woman should be X-rayed "if at any age she has concern and mammography is recommended by her physician . . . If she has large breasts, mammography is particularly important regardless of age because it is much more difficult to find a lump by palpation [physical examination]" The "urgent message" does not add that lumps are harder to find by mammography, too, in large breasts, or that there is no evidence that cancer is more common in large breasts. At a meeting of regional ACS officials in New York, the "urgent message" was offered to other divisions.
Meanwhile, Ca., a "journal for Clinicians" which the ACS distributes free to physicians and the press, took virtually the same line. So have articles bearing the ACS imprimatur in mass circulation magazines, the society's annual report and its current issue of Cancer News. In screened at the centers have been X-rayed - interim guidelines or no.
When queried about its mammography campaign, ACS insisted that the screening project is a "partnership" between the society and NCI. "The ACS is not pushing mammography for women under 50," said its vice president for public relations, Irving J. Rimer. "We're delineating women who are in high-risk group and we're saying to them, 'Talk to your doctor about the use of mammography.'"
Though there is little dispute that mammography may be justified for women at "high-risk," the definition of that term, as used in the "urgent message" and elsewhere, encompasses about 80 per cent of all women under 50, according to the ACS' own estimates.
No attempt has been made to explain the mathematical absurdity of why - when women have an 8 per cent risk of breast cancer in an entire lifetime - 4 out of 5 should be at "high risk" before reaching age 50.
While ACS sought to sway public and medical opinion against the interim guidelines - which are still in effect - three committees of experts appointed by NCI in October, 1975, were quietly engaged in studies that eventually hit the X-ray screening program like a bomb crashing into a munitions dump. Their conclusions, issued in March, were released in a tiptoe fashion wholly out of character with the usual practice of announcing major new about cancer research.
Only after one of the authors of this article made a freedom of information request was the material made public and then only a selected group of reporters was on the distribution list. Moreover, the information sheet accompanying the reports did not disclose the kernel of their contents, as is ordinarily done in such cases, and on the Friday before publication, Dr. Guy Newell, acting NCI director, Dr. Diane Fink, chief of the Division of Cancer Control, and Paul van Nevel, NCI's chief public information officer, hurried to New York at the behest of the ACS for a consultation. Asked why, Newell responded: "The ACS is very touchy about this project, you know."
What the studies strongly indicated, in short, is that the HIP data were badly interpreted and the NCI-ACS screening program was a mistake, possibly a very dangerous one for many of the 280,000 women involved.
The three committees had been assigned the task of assessing what is known about the risks and benefits of mammography in general and of re-examining the HIP data, a process that included a slide-by-slide review of breast tissue collected in that pioneering venture. Among their findings:
Of the 132 tumors that were detected in the course of the HIP project, 59 (almost 45 per cent) were missed by X-ray examination. Furthermore, "mammography was an ineffectual means of detecting minimal breast cancer" - i.e., cancers in a very early stage of development.
Mammography was best for finding the slow-growing types of cancer, which are not immediately destructive to surronding tissue and which, as it turns out, are the kind least likely to spread and kill. There may be little benefit to be had from finding these types early; some of them never require surgery other than a tissue biopsy and pose no threat to health and life.
Nearly 47 per cent of the aggressive tumore initially detected only by mammography were so large that they could have been detected simply by careful physical examination.
The report suggested, however, that the examination system was loaded in favor of mammography, X-ray examinations, its stated, were done on an "expert" basis, by well-trained physicians employing uniform techniques. The physical examinations are described as leaving "room for doubt about . . . quality and uniformity."
The three study groups urged "that mammography for routine screening of women under 50 years of age be discontinued," which they followed with what amounts to a death warrant for the entire screening program as it now stands:
"We recommend that further National Cancer Institute support of mammography in breast cancer screening of women over 50 now be concentrated on validating its use through appropriately designed randomized trials" - which means an end to indescriminate mass screening for "demonstration" purposes and a switch to reseach-oriented controlled studies.
The report, issued on the eve of the ACS' annual fund-raising drive, has evoked no public comment from AXS or NCI, which said it is awaiting still another report, now in the works, before making a decision on the fate of the program. But at other times, ACS has responded that mammography has inproved considerably since then, and will further improve in safety and reliability.
However, some of the available evidence on this claim is not comforting. For example, in the March 7 issue of the Journal of the American Medical Association, Dr. Gerson Lesnick of the Mt. Sinai School of Medicine, New York, reports that in a group of 106 breast cancer surgery patients under age 45, 84 per cent of the tumors were detected by the patients themselves; only 2 per cent were detected only by mammography. In 63 per cent of these cancer cases, X-rays failed to detect the disease.
On the basis of these findins, he reported, surgery was deferred in 15 cases, thus giving the disease additional time to advance.
Meanwhile, although the first tumors found by the ACS-NCI screening project were reported about four years ago, the data has been made available exclusively to the society and detection center directors. Thus, Bailar and an NCI consultant who have asked to look at the data have been denied the opportunity and no one knows how many of the growths found may prove to have been either non-malignant or cancers of the slow-growing types which could safely have awaited discovery by other means. But even assuming that none of the tumors fit these descriptions, the cost per case found by mammography alone is upward of $75,000.
With the 5-year "demonstration" program at about its midpoint, the ACS-led cancer lobby can now be expected to put new energy into the old formula of fear and hope, checks and checkups. The opening signal came last November in a presentation of old arguments in Ca., ACS' journal for physicians, under the title of "Restoring Confidence in Mammography."
What really needs to be restored, however, is some backbone in the National Cancer Institute, which, after all, is the public's guardian against a disease that threatens us all.
While 280,000 women have participated in the NCI-ACS breast cancer detection project, many more have been spurred by fear of the disease to be screened by mammography in doctor's offices and hospitals. There, unfortunately, the equipment may not be calibrated to deliver minimal radiation. Nor is there assurance that the technicians are properly supervised or even trained. Only New York, New Jersey and California require X-ray technicians to be licensed andno states require periodic reviews of competence.
As a result, many women have probably been exposed to excessive radiation. For example, Dr. Alfed S. Ketcham, professor of surgery at the University of Miami, reported having seen in 18-year-old girl who, without having first had her breasts examined manually, had three sets of breast X-rays in a week. He also cited the case of a 32-year-old woman who had 27 mammograms within seven years.