“A document in perspective” is a new feature of the Cancer History Project.
The objective is to take a noteworthy document—be it prescient or naive—and illuminate it by placing it in proper historical and scientific context.
We begin with a 1975 report by then NCI Director Frank J. Rauscher, Jr. The report’s title—Cancer Program is Well Underway—reflects the triumphalism of its time. The National Cancer Act was signed not quite four years earlier, and the most optimistic of its boosters had promised the cure by the U.S. Bicentennial a year hence.
The document is put in perspective by Otis W. Brawley, the Bloomberg Distinguished Professor of Oncology and Epidemiology, Johns Hopkins University and co-editor of the Cancer History Project.
“In this press report, issued four years after the signing of the National Cancer Act, Dr. Frank Rauscher, then director of the National Cancer Program and the National Cancer Institute discusses progress in implementation of the National Cancer Act,” Brawley writes.
“This type of report was common in trying to maintain momentum and public support for the National Cancer Program. Dr. Rauscher emphasizes that the goal of the National Cancer Act was “development and application of the means to reduce cancer incidence, morbidity, and mortality among the population of the United States.”
As editors of the Cancer History Project, we invite our collaborators to suggest other documents—and use this format to put them in perspective.
Cancer Program is well underway
Frank J. Rauscher, Jr., Ph.D.
Director, National Cancer Program
National Cancer Institute
January 15, 1975
U.S. Medicine
Reprinted by the U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE
National Institutes of Health
Under the National Cancer Act Amendments of 1974, the National Cancer Program (NCP) is now well into its second three-year authorization.
The NCP has moved forward under its various mandates in the past year in activities aimed at forging a national focus for the ultimate conquest of cancer. The activities have been designed to work toward that goal by initiating immediately development and application of the means to reduce cancer incidence, morbidity, and mortality among the population of the United States.
Progress has been made, first, in the research mandate, which provides for scientific efforts ranging from basic research on cancer biology to applied research on all aspects of the management of cancer.
Second, progress has been made in the cancer control, or demonstration and communication, mandate, which provides for bridging the gap between knowledge produced through research and its general application in people.
Third, progress has been made in coordination of NCP activities. Advances were made in establishing and expanding the interrelationships between the programs of the National Cancer Institute and other relevant federal and non-federal programs required for the most expeditious use of the national resources for cancer.
Such interrelationships are fostered through a variety of programs, such as cancer centers, organ-site task forces, cancer control program, international activities, and the extramural program, which supports grants, contracts, and interagency agreement.
Progress against breast cancer
Among the highlights of progress reported during the year, the advances against breast cancer are especially worthy of note.
In American women, the breast is the leading site of cancer incidence (90,000 last year) and deaths (33,000), and its mortality rate has not been significantly reduced in the past 35 years, despite all efforts. The first results from an intensive program mounted by NCI’s breast cancer task force to improve the diagnosis and treatment of this dreaded disease were reported in September at a symposium for practicing physicians.
One of the reports was on results from a nationwide breast cancer screening demonstration program sponsored jointly by the American Cancer Society and NCI.
It indicated an increase in the percentage of women who did not have cancer in the regional lymph nodes at the time their breast cancer was diagnosed.
About 75 percent of approximately 300 symptom-free women whose breast cancer was detected by the screening program had cancer-free nodes, as compared with the usual figure in the United States of 45 per cent. Patients whose nodes are free of cancer at the time of diagnosis have a 5-year survival rate of about 75 per cent and a 10-year survival rate of about 65 per cent. But women with positive nodes have a 5-year survival rate of about 50 per cent and only about 25 per cent live 10 years.
The NCI-ACS program involves some two dozen breast cancer screening projects, which will screen annually up to 270,000 women 35 years of age and older with a physical examination, X-rays (film mammography or xeroradiography), and thermography.
An NCI-supported study has shown that early detection does decrease breast cancer death rates. A group of 31,000 women screened for breast cancer by a combination of physical examination and x-ray mammography had a one-third reduction in breast cancer deaths over a 5-year follow up period. One-third (44 out of 132) of the breast cancers detected in the study were found by mammography before the tumors were large enough to be detected physically. Forty-three of these 44 women survived their disease during the 5-year period, indicating that early detection led to increased effectiveness of treatment.
Another report to the symposium was on a large clinical study conducted by the national surgical adjuvant breast project to determine the optimal treatment for primary breast cancer. The study involves 34 institutions and some l,700 patients.
Results after two years show that, in women with clinically negative nodes treatment with total mastectomy (removal of the breast only), total mastectomy with radiotherapy of the chest, or radical mastectomy yielded essentially equal recurrence rates.
In women whose disease involved the breast and axillary nodes, radical mastectomy or total mastectomy combined with postoperative radiotherapy also yielded essentially equal recurrence rates. The recurrence rate for the latter group was 35 per cent, about twice that for the group without apparent spread of cancer outside the breast.
A new, larger study is being organized to extend the observations, and possibly to include a determination of the effectiveness of “lumpectomy,” surgical removal of the tumor but not the entire breast.
A second treatment study, aimed at metastatic disease, is investigating the use of postoperative systemic chemotherapy in women who were found at surgery to have positive axillary nodes. The study encompasses 37 hospitals and about 250 patients.
Brawley: Dr. Rauscher declares that there has been progress in the research mandate, as well as in cancer control, and in coordination of activities in the National Cancer Program. Specifically, he lauds progress in breast cancer.
This was just after the wife of the president, Betty Ford, and the wife of the vice president, Margaretta (Happy) Rockefeller had both been diagnosed and treated for breast cancer. It was also just several years after the first prospective randomized study to suggest the x-ray of the breast or mammography reduced risk of death.
The reader will note that orthodox epidemiology had not yet arrived at NCI. There are several times when surrogates for reducing the number of deaths are espoused. The report talks a great deal about finding tumors early or increasing the number or proportion surviving five years.
There would be a series of arguments in The New England Journal of Medicine in the mid-1980s as to what is evidence of progress. It’s an argument that continues to this day as survival statistics are frequently misused to claim progress.
The data after two years indicated that the rate of cancer recurrence was significantly reduced for women receiving L-phenyl-alanine mustard (LPAM), an oral anticancer drug.
The results were particularly striking in premenopausal women: 1 out of 30 patients receiving L-PAM had recurrence, as compared with 11 out of 37 receiving a placebo. For postmenopausal women, the recurrence rates were also reduced in the L-PAM-treated group, but not as markedly.
The L-PAM treatment produces minimal side effects and can be widely used. Further studies of drugs, in combination with L-PAM, in other combinations, and including the addition of immunostimulants, such as the attenuated tubercle bacillus, BCG, and another bacterial agent, C. Parvum, are planned.
The meeting also included a report on research to determine the role of hormone receptors (estrogen-binding proteins) in predicting response to hormone therapy.
Using these markers, investigators found that 63 patients (97 per cent) in a group of 65 had abnormal levels of at least one of these markers. In a group of 15 post-operative patients with positive nodes, 10 (67 per cent) had elevated levels.
Altogether, the findings from the two-year report of the breast cancer task force suggest that less-than-radical surgery may be acceptable for treatment of primary breast cancer and that subclinical metastasis may be successfully treated with drugs.
The response of an individual patient to such therapy can be predicted on the basis of a laboratory determination of whether cancer cells removed at surgery carry a hormone receptor on their surfaces. About 50 per cent of biopsies of breast cancer contain the receptors. Those who will respond can receive ·hormone therapy, and non-responders can be given other therapies without delay.
Another report dealt with the research to improve the assessment of tumor burden by measurement of levels of biologic markers-substances found in the blood or urine correlating with the presence of tumor.
Ideally, levels of these substances will be high in the presence of tumor in the patient and should decrease as the tumor responds to therapy. Out of eight biologic markers studied, three (human chorionic gonadotrophin, HCG; carcinoembryonic antigen, CEA; and a transfer RNA nucleoside N2N2dimethyl-guanosine) were found to be present in abnormal amounts in breast cancer patients.
If the results from numerous other studies of combination therapy are similarly encouraging, including the use of one or more of the drugs known to be effective against breast cancer, both the cure and survival rates should be improved substantially. (Alkylating agents such as cytoxan; antimetabolites, such as 5-fluorouracil and methotrexate; vinca alkaloids, such as vincristine; and antitumor antibiotics such as adriamycin. Combination; such as 5-FU, cytoxan, and predni-. sone; cytoxan, 5-FU, and methotrexate; and cytoxan, 5-FU, and adriamycin.) At the same time, the degree of disfigurement due to radical mastectomy should be reduced.
Brawley: The reader will note Dr. Rauscher lauds the use of a number of chemotherapies at the time. Among them L phenylalanine mustard or LPAM, CCNU and some that are still commonly used such as cyclophosphamide, methotrexate, leucovorin. There is mention of some of the original modern day attempts at immunotherapy with BCG in breast cancer and melanoma.
This press release has some of the earliest discussion of measuring the estrogen receptor in breast cancer and the use of tumor markers to follow the course of disease and there was even speculation about tumor markers for screening.
Is also most interesting that he highlights the National Cancer Institute-American Cancer Society Breast Cancer Demonstration Project. This program, which began in 1972, would enroll more than 270,000 women ages 35 to 74 and provide them with physical examination and mammography or thermography of the breast.
It was lauded for showing a one third reduction in breast cancer deaths over a five-year period of time among women getting mammography and the fact that the procedure clearly resulted in earlier detection.
A little piece of history not in this press release. This would become an example of when science is implemented too fast.
The value of mammography had yet to be fully assessed and radiologists were not adequately trained to read mammography and pathologists were not adequately trained to read breast biopsies.
Two years later, a reference pathologist would review the 506 so-called minimal breast lesions found in this study and 66 of the 506 lesions were determined not to be invasive cancer nor ductal carcinoma in situ (Greenberg et al, 1976)(Culliton, 1976).
Almost all those 66 women had already received definitive therapy, which at the time was usually a Halsted radical mastectomy. An audit of the mammography equipment used in the study also found that radiation dosing and quality of equipment was highly variable (Fischer et al, 1998) (Destouet et al, 2005).
Sources:
- Greenberg DS . Medicine and public affairs. X-ray mammography—background to a decision. N Engl J Med . 1976;295:739–740
- Culliton BJ . Breast cancer: second thoughts about routine mammography. Science . 1976;193:555–558 .
- Fischer R , Houn F , Van De Griek A , et al. The impact of the Mammography Quality Standards Act on the availability of mammography facilities. Prev Med . 1998;27:697–701 .
- Destouet JM , Bassett LW , Yaffe MJ , ButlerPF , Wilcox PA .The ACR’sMammography Accreditation Program: ten years of experience since MQSA. J Am Coll Radiol . 2005;2:585–594 .
Combination therapy of cancer
Growing clinical evidence confirms the concept that combinations of therapeutic methods tailored to have a maximum impact on individual cancers produce significantly increased survival rates. Numerous clinical studies conducted and supported by NCI have shown the effectiveness of combination therapy against many types of cancer.
Among the recent progress reports are the following: In one type of lung cancer (oat cell), a response rate of more than 50 per cent and a significant prolongation of survival were achieved using a drug combination of cytoxan, methotrexate, and CCNU [1-(2-chloroethyl)-3-cyclohexyl-I-nitro-sourea].
In advanced non-Hodgkin’s lymphomas, combination chemotherapy programs have produced complete responses in 45 per cent of 80 patients, with a median duration of about 4 years. Cytoxan, vincristine, and prednisone; nitrogen, mustard, vincristine, procarbazine, and prednisone; and cytoxan, vincristine, procarbazine, and prednisone.)
In advanced ovarian cancer, a four-drug combination of cytoxan, hexamethylmelamine, 5-fluorouracil, and methotrexate has produced an overall response rate of more than 70 per cent, as compared with 45 per cent for standard, single agent, PAM therapy. Treatment with a drug (BCNU) combined with radiotherapy following initial surgery has been shown effective against malignant gliomas of the brain. Median survival was 40 weeks as compared with 14 weeks in untreated patients.
Chemoimmunotherapy of malignant melanoma with a combination of a drug (dimethyl triazeno imidazole carboxamide, DTIC) and BCG produced a remission rate of 55 per cent m a group of patients with lymph-node metastasis, as compared with a rate of I 8 per cent for patients treated with chemotherapy alone. The duration of remissions and survival was significantly longer for patients treated with DTIC and BCG.
Similar results have been obtained with a multimodality approach to the treatment of childhood cancers.
In osteogenic sarcoma, surgery and infusion of large doses of methotrexate, followed by citrovorum factor to protect against the toxicity of the anticancer drug, have produced regressions of metastatic pulmonary lesions and increased survivals.
A report of followup of 4 to 12 months among 121 patients indicated that about 80 per cent had no evident disease; these results compare favorably with the usual 50-per cent survival at 6 months. Adriamycin is also being used in some studies.
The National Wilms’ Tumor Study, another example of a cooperative, multidisciplinary approach, has shown the effectiveness of combinations of surgery, radiation therapy, and drugs, such as vincristine and actinomycin D. Overall 3-year survival rates of 60 per cent have been reported, and in certain early stages of the disease, survivals are approaching 100 per cent.
The message of the treatment research results is that there is a need for rethinking the approaches to the management of a broad spectrum of cancers. In the current thinking of research clinicians, planning for treatment must recognize that cancer usually is not a localized phenomenon, and that the use of drugs should be introduced earlier in the treatment schedule, before the cancer is far advanced.
The NCP has implemented its clinical program of treatment research to take advantage of combinations of methods in the primary treatment of local and regional disease, and disseminated disease.
In addition, research continues on the various treatment methods–surgery, radiotherapy, chemotherapy, and a possible new tool, immunotherapy; on drug development; and on studies in cellular control mechanisms that should lead to the design of increasingly effective antitumor agents.
Research progress in diagnosis and prevention
On the premise that early diagnosis is crucial to effective treatment, and that prevention is the best possible approach to the management of cancer, NCP activities in these areas have moved in a number of directions.
Among the advances, improved early detection has yielded encouraging results in lung cancer. In the early results of a large clinical trial of sputum cytology and chest x-ray to detect lung cancer before symptoms appear in heavy smokers, the cancers found were much smaller than in patients with symptoms.
In the burgeoning research area of immunodiagnosis, more than 25 potential immunodiagnostic tests for cancer were evaluated with the aid of a bank of stored serum specimens. In one evaluation, a test for a new purified fraction of carcinoembryonic antigen (CEA) was positive in about 50 per cent of patients with gastrointestinal cancer; there were very few false positives. This high level of discrimination is a major advance in improving the CEA test as an aid in the diagnosis of cancer.
In research on cancer cause and prevention, preliminary reports were issued from the Third National Cancer Survey, which collected demographic and medical information on all cancers newly diagnosed during the three year period 1969-71 in seven metropolitan areas and two entire states.
Among the important findings were indications of a significant increase in cancer among U.S. black men, particularly cancer of the prostate and the esophagus, and a trend toward a more uniform incidence of cancer across the country.
It was also found that the most frequent site of cancer for both men and women is the large intestine, and that skin cancer occurs much more often than hitherto estimated.
Another new publication that is expected to provide a valuable tool for research leads to cancer risk by region is a compendium of cancer mortality data for each county in the country for the period, 1950-69.
An indication of a link between diet and cancer of the colon resulted from a study of Japanese migrants to Hawaii. The risk of developing colon cancer increased as this population of Hawaiian residents of Japanese descent adopted a western diet high in beef.
More and more evidence accrues to confirm the belief that environmental agents and social practices, rather than genetic factors, are largely responsible for variations in occurrence of cancer in different populations. In this context, the possibility of developing means for preventing cancer becomes an increasingly achievable goal.
Research in many scientific disciplines—immunology, cell biology, molecular biology, viral oncology, and chemical and other environmental carcinogenesis—is producing new information on the nature of the cancerous change from the normal state of an organism. Such new findings are incorporated into the research strategy aimed at ultimately developing the means to prevent cancer or diagnose it as early as possible in the course of the disease.
Brawley: Dr. Rauscher spends significant time discussing the Cancer Control Program. He heralds the publication of the third National Cancer Survey, which collected demographic and medical information in seven metropolitan areas from 1969 to 1971. This paper discussed variation in the occurrence of cancer and the likelihood that environmental agents play a substantial role rather than genetics.
Cancer control program
Progress has been made in disseminating information on cancer nationwide into general use primarily through the cancer control program. This program engages in field testing, demonstration, and development of model systems, rather than delivery of health care. It aims to systematically disseminate “practice-ready” research information on all aspects of cancer: prevention, detection and diagnosis, treatment, and rehabilitation and continuing care.
In its first full year of activity more than 100 contracts and grants were awarded across the country. Most states have cancer control projects within their borders and some have connections with cancer control activities in other States through network arrangements with nearby primary cancer control institutions. These projects are organized to assure active involvement of community hospitals, family physicians, state and local health departments, medical societies, lay and voluntary organizations, and other community resources.
In recognition of the fact that the best defense against death due to cancer is early diagnosis, the cancer control program placed a major emphasis on detection projects. These included the breast cancer screening projects already cited, projects established with 20 state health departments for uterine cervical cancer screening, and a few projects for lung cancer detection.
To assure optimal treatment for cancer patients throughout the country is another major objective of NCI’s cancer effort. Effective cancer therapy requires an integrated approach involving the clinical oncologist, surgeon, radiotherapist, and pathologist.
This team should begin with diagnosis of the extent of the patient’s disease in order to make decisions about combining surgery, irradiation, and anticancer drugs early in the treatment. The family physician should join this team to guide the course of diagnosis, treatment, and recovery.
Through a series of demonstration projects involving networks of cooperating community physicians and hospitals linked to major hospitals, the latest information on cancer treatment is disseminated.
The types of cancers currently being emphasized are breast cancer, head and neck cancer, acute leukemia of childhood, Hodgkin’s disease, and non-Hodgkin’s lymphomas. The primary hospital in the network may be an NCl-funded cancer center, or a centrally located hospital with a large cancer patient load. A wide range of consultation possibilities and care facilities will thus become available to the cancer patient.
As soon as possible in the cancer treatment process, attention should be given to rehabilitation of the patient. NCI is funding a wide range of projects demonstrating rehabilitation facilities, techniques, services, and training for professional and auxiliary health workers.
For example, a model patient rehabilitation service system is being developed to provide medical, psychological, and social support required to return the cancer patient to a normal and productive life.
Progress was also made in disseminating cancer knowledge through development of community outreach programs under the aegis of comprehensive cancer centers and clinical cooperative groups. Nine programs are being supported for development of methods to extend cancer control efforts to community hospitals, practicing physicians, and the general public.
Brawley: Dr. Rauscher discusses the beginning of what will become the Community Clinical Oncology Program as it tries to link cancer centers to doctors practicing medicine in the community.
This is a time when there are very few medical oncologists practicing in the community. Indeed, medical oncology programs would be building at this time and would ultimately start providing practitioners in the community in the 1980s.
NCI would eventually launch the community clinical oncology program or CCOP program which is now known as the National Community Oncology Research Program (NCORP).
The press release discusses programs and rehabilitation. This is an early effort at the promotion of cancer patient survivorship programs.
Cancer centers and cooperative groups
The NCI has also moved ahead under its mandate to establish comprehensive cancer centers. These will constitute a nationwide network of institutions whose purposes are to conduct a broad range of cancer research , projects and to develop and demonstrate the best methods of cancer prevention, diagnosis, treatment, and rehabilitation. The number of recognized cancer centers was increased by five during the year to a total of 17.
Fourteen are developing comprehensive cancer center programs: Fox Chase Cancer Center, affiliated with University of Pennsylvania, Philadelphia; the Sidney Farber Cancer Center, Boston; Colorado Regional Cancer Center, Denver; Duke University Medical Center, Durham; Georgetown University-Howard University Comprehensive Cancer Cancer Program, Washington, D.C.; Fred Hutchinson Cancer Research Center affiliated with the University of Washington, Seattle.
lllinois Cancer Council, Chicago; the Johns Hopkins Medical Institutions, Baltimore; the Mayo Foundation, Rochester, Minnesota; University of Southern California (with the Birmingham; University of Miami School of Medicine, Miami; University of Southern California (with the Los Angeles County Department of Hospitals), Los Angeles; the University of Wisconsin Medical Center, Madison; and Yale University Medical School, New Haven.
Three other institutions were recognized as having Comprehensive Cancer Centers at the time of enactment of the National Cancer Act of 1971: M.D. Anderson Hospital and Tumor Institute, Houston; Memorial Sloan-Kettering Cancer Center, New York; and Roswell Park Memorial Institute Buffalo.
NCI supports specialized cancer centers to conduct research in specialized or well defined areas, such as chemotherapy or pediatrics; clinical cooperative groups to treat patients with various forms of cancer under specified research protocols; and organ-site task forces to study laboratory and clinical aspects of cancer of the breast, lung, large bowel, bladder, and prostate.
Large numbers of patients hopefully will benefit from the treatment methods resulting from the various research and demonstration activities. The physicians participating in the centers programs, cooperative research trials, and task forces will use the treatments on a non-research basis for many cancer patients not participating in studies.
International cancer research data bank program
Another of NCP mandates for which progress is reported is the implementation of a major new communication activity, the International Cancer Research Data Bank (ICRDB) program. Its objective is to actively promote and facilitate worldwide exchange of information between cancer scientists and dissemination of information to all physicians, through cancer centers and other appropriate organizations.
There will be four major segments of the ICRDB program: cancer information dissemination and analysis centers, scientist-to-scientist communication, clinical cancer data methods, and special cancer information projects.
At the present time, a specialized cancer database has been developed by the National Library of Medicine in collaboration with NCI, and made available to scientists.
The system, called Cancerline, contains about 15,000 cancer chemotherapy abstract; these are now available for all on-line search throughout the United States to all scientists with access to a terminal linked to the NLM computer network.
In addition, the data can be repackaged to the special needs of practicing physicians, managers, educators, and other audiences. These abstracts represent the best published information, and can be immediately retrieved with printout if desired. This system permits search according to author, disease, drug, and other factors.
The ICRDB program also is negotiating an interagency agreement with the Smithsonian Science Information Exchange to produce an additional 10,000 descriptions of ongoing cancer research projects.
At the same time, negotiations are under way with the International Union Against Cancer for expanding the coverage of its clinical protocol registry and computerization of its information. The additional information obtained through these agreements will be added to the NLM data bank and be available for on-line searching throughout the United States.
In conclusion, we are constantly aware that the NCP is unique for the federal government and for medicine. It has responsibility not only to conduct and foster cancer and related research, but to coordinate all cancer research done in the United States and to establish interrelationships in other countries as well.
Furthermore, it has an additional important responsibility to encourage the immediate application of knowledge gained from research to the cancer patient and the prospective cancer patient.
The legislative mandates have also provided an unprecedented opportunity for an intensive, coordinated attack on cancer, which is now in full operation.
Remarkable recent progress has been made in detection of cancer risk for some types of cancer, in early diagnosis, in treatment and rehabilitation, and in prevention.
All told, the outlook is brighter than it was for reducing the impact of cancer from its present status as the most dreaded disease of Americans.
