EDITORIALS
brain. The psychobiology of all of these synaptic transmitters and modulators remains less clear and our knowledge is fragmentary. There is enough information to indicate quite clearly that they interact with each other in complex patterns to mediate aversive and appetitive behavior, attention, memory and mood. How they do so, and what derangements in their normal function occur in the major mental illnesses are questions that can now be plausibly addressed. SEYMOUR S. KETY, MD
Professor of Psychiatry
Harvard Medical School
Boston
REFERENCES 1. Klein DF, Davis JM: Diagnosis and Drug Treatment of Psychiatric Disorders. Baltimore, Williams & Wilkins Co., 1969 2. Swazey J: Chlorpromazine in Psychiatry; A Study of Therapeutic Innovation. Cambridge, MIT Press, 1974 3. Heston LL: Psychiatric disorders in foster home reared children of schizophrenic mothers. Br J Psychiatry 112:819-828, 1966 4. Kety SS, Rosenthal D, Wender PH, et al: Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic: A preliminary report based upon psychiatric interviews, In Fieve R, Rosenthal D, Brill H (Eds): Genetic Research in Psychiatry. Baltimore and London, The Johns Hopkins University Press, 1975, pp 147-165 5. Usdin E (Ed): Neuropharmacology of Monoamines and their Regulatory Enzymes. New York, Raven Press, 1974 6. Snyder SH: The dopamine hypothesis of schizophrenia: Focus on the dopamine receptor. Am J Psychiatry 133:197-202,
1976
SPECIAL EDITORIAL
Radiation Risks of Mammography IN THIS DECADE of increased public awareness of environmental hazards, it is hardly surprising that extensive publicity be given to statements on the potential carcinogenic effects of widely-used x-ray examinations. Such adverse publicity has recently been circulated concerning mammography, publicity that unfortunately contains many inaccuracies and gross overstatements. Mammography is a valuable diagnostic tool for detection of breast cancer. When used in conjunction with physical examination, the diagnosis of carcinoma can be made with a high degree of accuracy, especially in women over age 50.1-3 Mammography is particularly useful in discovering early breast cancer. Fully a third of the early cancer found among asymptomatic women is found by mammography alone;4'5 this applies equally to women above and below age 50.6 Despite these proved advantages, the full bene-
fits and potential risks of mammography are not fully known. For these reasons and others the American Cancer Society (ACS) and the National Cancer Institute (NCI) jointly are sponsoring a nationwide breast cancer detection project designed to screen 270,000 asymptomatic women. It is hoped that this project will result in a determination of the proper role that mammography should play in detection of early breast cancer. Specifically, information should be forthcoming on (1) the optimal age for the initial mammogram, (2) the proper frequency of screening mammograms and (3) whether or not there are significant long-term radiation risks. There is a wealth of information on the carcinogenic effect of large doses of x-rays (100 rads or more). However, despite numerous controlled animal experiments and extensive epidemiologic analyses of human cancer, remarkably little is known of the sequelae of low doses of radiation, especially in the range in which mammography now functions (0.5 to 5 rads surface dose, breast tissue dose substantially lower). In fact, there is no hard evidence of x-ray induction of cancer in any adult human being with radiation doses less than 50 rads;7 specifically for the breast this limit appears to be 90 rads.8-11 In order to apply the data from high-dose studies to the much lower doses used in diagnostic radiology, most radiobiologists construct a doseresponse curve and extrapolate linearly back toward zero, assuming that there is no threshold dose below which carcinogenic effects are absent. However, this type of approach is misleading, especially since the calculations result in highly specific conclusions having the ring of scientific accuracy. In fact, such analyses are based on assumptions that have never been proved, and about which there is considerable disagreement.'2-14 Conclusive evidence does not exist for either a linear dose-response curve or lack of a threshold dose.12-'5 Therefore, even the most impressive statistical analysis that leads to these assumptions must be considered inaccurate, with the probability that this inaccuracy will result in significant overestimations of risk.15-16 The recent analyses that have received national press coverage attempted to evaluate the benefits and cumulative radiation risk of multiple mammographic examinations in asymptomatic women. These analyses by Bailar16 and Breslow17 were based on the best available study (the HIP [Health Insurance Plan of Greater New York] study) of THE WESTERN JOURNAL OF MEDICINE
493
EDITORIALS
screening mammography, begun in 1963, which showed a substantial reduction in breast cancer mortality only for women over age 50.1,5 Breslow used the HIP study to conclude that screening mammography under age 50 was not recommended, but that the benefits outweighed the risks in women over 50. Neither Breslow nor Bailar attacked the advisability of single mammographic examinations, probably since the resultant radiation doses were so small. However, both analyses suffer from two serious weaknesses: (1) the risk analysis was based on the unproved assumptions of a linear dose-response curve and lack of threshold dose and (2) no allowance was made for the improvements in mammographic equipment, technique and knowledge that have accrued in the greater than ten-year interval since the HIP study mammograms were taken. These improvements are illustrated by preliminary data from the breast cancer detection project, which show that a third of the breast cancer so far detected has been in women under age 50, and that 45 percent of this cancer was detected by mammography alone.6 Unfortunately, the effects of the Bailar and Breslow analyses have been quite far-reaching, almost certainly due to extensive and misleading lay press coverage. By elevating what are in fact unproved estimates of risk to the status of scientific acceptance, the press has unduly alarmed the public about radiation hazards of mammography. This error is further compounded by grossly overstating the conclusions to apply to all mammography situations rather than only to multiple screening examinations in women under age 50. Headlines such as "Breast Cancer: Does One Exam Cause a Tumor?"'8 are to be deplored. One adverse effect of this publicity has been a substantial reduction (as much as 30 to 40 percent) in mammographic examinations across the country, not only among asymptomatic women above and below age 50 but also in women with signs and symptoms suggesting the presence of breast cancer. Of the many women who are now avoiding mammography, some most probably have early cancer detectable only by the examination they have been misled to refuse. This will inevitably result in isolated individual tragedies. More disturbing is the recent decision of the ACS and NCI to recommend against mammography for asymptomatic women aged 35 to 50 in their nationwide screening centers. This amounts to abandonment of a portion of the breast cancer 494
DECEMBER 1976 * 125 * 6
detection project, a step backwards which will result in loss of the very benefit-versus-risk data that promise to indicate accurately the extent to which screening mammography is advisable. It is ironic that the ACS-NCI decision is based on the same inadequate and probably inaccurate data that helped prompt the breast cancer detection project in the first place; and it is unfortunate that the ACS and NCI seem to have based their decision on public reaction to misleading and overstated media reports rather than on any conclusive scientific evidence. Now is the time to put the situation straight. To that end I offer the following suggestions. (1) Mammography should remain an integral part of the evaluation of women who have symptoms or physical findings suggestive of breast cancer, regardless of age. (2) Screening mammography in asymptomatic women over 50 should continue to be done at regular intervals since even now there is general agreement that its benefits outweigh the risks. (3) The ACS and NCI should reverse their decision and encourage screening mammography in asymptomatic women in the 35 to 50 age group. The data to be compiled from the nationwide breast cancer detection project currently offer the best hope for determining the proper role for mammography for women of all ages. Let us not abandon this hope because of admittedly insufficient risk evidence, especially since preliminary findings of the screening project indicate substantial benefits for women under 50. (4) Mammography should be carried out at the lowest possible radiation dose consistent with current diagnostic accuracy. Radiologists should strongly consider using high-filtration xeroradiographic techniques or the even lower dose screenfilm systems that have recently been marketed. Mammography done in this fashion produces a fourth or less radiation than assumed in the calculations of Bailar, and even allowing for his inaccurate analytic methods would shift his conclusions clearly in favor of mammography. All involved in the current mammography controversy agree that we know too little about radiation risks to draw firm conclusions. Some, relying heavily on the "best" evidence now available, would limit the scope of mammography until more conclusive data can be generated. I must remind them, however, that no animal experiments and no retrospective statistical analyses can produce data any more meaningful than those which are available now. Rather, we must design
-EDITORIALS
prospective clinical studies to determine benefits and risks as accurately as possible. Such studies, of course, should require informed consent of all participants. The most promising attempt to date has been the joint ACS-NCI project. Mammography is already known to be beneficial for symptomatic patients of all ages and for the screening of asymptomatic women over 50. Let us now find out whether this also applies to the screening of women under 50 by proceeding with the breast cancer detection project without alteration or delay. EDWARD A. SICKLES, MD Chief, Mammography Section Department of Radiology University of California, San Francisco
REFERENCES 1. Strax P, Venet L, Shapiro S: Value of mammography in reduction of mortality from breast cancer in mass screening. Am J Ronetgenol 117:686-689, 1973 2. Stark AM, Way S: The screening of well women for the early detection of breast cancer using clinical examination with thermography and mammography. Cancer 33:1671-1679, 1974 3. Sadowsky NL, Kalisher L, White G, et al: Radiologic detection of breast cancer-Review and recommendations. N Engl J Med 294:370-373, 1976
EDITOR'S NOTE: The above editorial was sent to Lester Breslow, MD, for comment. Dr. Breslow's views are presented below. A reply from Dr. Sickles will appear in the Correspondence section next month.
Radiation Risks of Mammography: Another View IT IS PROBABLY TRUE that recent and unfortunately sometimes misleading publicity has created some undue alarm about the risks of mammography. Matters are not set straight, however, by statements such as that of Sickles. He touches mainly on two points. One point advanced by Sickles can be represented by quoting from his editorial: ". . . potential risks of mammography are not fully known." most radiobiologists construct a doseresponse curve and extrapolate linearly back toward zero, assuming that there is no threshold below which carcinogenic effects are absent." ". . . such analyses are based on assumptions that have never been proved, and about which there is considerable disagreement. Conclusive
4. Wolfe JN: Analysis of 462 breast carcinomas. Am J Roentgenol 121:846-853, 1974 5. Strax P: Control of breast cancer through mass screening. JAMA 235:1600-1602, 1976 6. Preliminary unedited (current) statistics, Breast Cancer Detection Demonstration Project, Bethesda, Md, Jul 19, 1976 7. Margulis AR: The lesions of radiobiology for diagnostic radiology. Caldwell Lecture, 1972. Am J Roentgenol 117:741756, 1973 8. MacKenzie I: Breast cancer following multiple fluoroscopies. Br J Cancer 19:1-8, 1965 9. Wanebo CK, Johnson KG, Sato K, et al: Breast cancer after exposure to the atomic bombings of Hiroshima and Nagasaki. N Engl J Med 279:667-671, 1968 10. Myrden JA, Hiltz JE: Breast cancer following multiple fluoroscopies during artificial pneumothorax treatment of pulmonary tuberculosis. Canad Med Assoc J 100:1032-1034, 1969 11. Mettler FA Jr, Hempelmann LH, Dutton AM, et al: Breast neoplasms in women treated with x-rays for acute postpartum mastititis-A pilot study. J Nat Cancer lnst 43:803-811, 1969 12. Rossi HH, Kellerer AM: Radiation carcinogenesis at low doses. Science 175:200-202, 1972 13. Mole RH: Ionizing radiation as a carcinogen: Practical questions and academic pursuits. Br J Radiol 48:157-169, 1975 14. Morgan KZ: Reducing medical exposure to ionizing radiation. J Am Industr Hyg Assoc 36:358-368, 1975 15. National Council on Radiation Protection and Measurements: Review of the Current State of Radiation Protection Philosophy. NCPR Report No. 43. Washington, National Council on Radiaticn Protection, 1975 16. Bailar JC III: Mammography: A contrary view. Ann Intern Med 84:77-84, 1976 17. Breslow L: Unpublished data, released Jul 15, 1976 18. San Francisco Chronicle: Jul 29, 1976, p 17
evidence does not exist for either a linear doseresponse curve or lack of a threshold dose." In our report to the National Cancer Institute of 15 July 1976,1 we stated: "The basis for believing that mammography may induce breast cancer lies in a series of studies indicating that exposure of the breast to radiation can cause breast cancer. These studies show that women (a) exposed to radiation in the Japan atomic bomb explosion;2-4 (b) treated by radiation for benign breast disease;5 or (c) subjected to repeated x-ray fluoroscopy of the chest in connection with treatment for tuberculosis,6-'0 all suffered a significantly higher incidence of breast cancer in later years than did comparable groups of women considered as controls. Although the amount of radiation exposure in these series of women was many times greater than that encountered in mammography, a National Academy of Sciences review indicated (and we concur) that one must assume a linear dose-response relationship on the basis of present evidence and in the absence of any clear information to the contrary." This means that there is no absolutely safe dose and that, in the case of breast cancer induced by x-rays, the number of cases resulting from the exposure will be simply proportional to THE WESTERN JOURNAL OF MEDICINE
495
brain. The psychobiology of all of these synaptic transmitters and modulators remains less clear and our knowledge is fragmentary. There is enough information to indicate quite clearly that they interact with each other in complex patterns to mediate aversive and appetitive behavior, attention, memory and mood. How they do so, and what derangements in their normal function occur in the major mental illnesses are questions that can now be plausibly addressed. SEYMOUR S. KETY, MD
Professor of Psychiatry
Harvard Medical School
Boston
REFERENCES 1. Klein DF, Davis JM: Diagnosis and Drug Treatment of Psychiatric Disorders. Baltimore, Williams & Wilkins Co., 1969 2. Swazey J: Chlorpromazine in Psychiatry; A Study of Therapeutic Innovation. Cambridge, MIT Press, 1974 3. Heston LL: Psychiatric disorders in foster home reared children of schizophrenic mothers. Br J Psychiatry 112:819-828, 1966 4. Kety SS, Rosenthal D, Wender PH, et al: Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic: A preliminary report based upon psychiatric interviews, In Fieve R, Rosenthal D, Brill H (Eds): Genetic Research in Psychiatry. Baltimore and London, The Johns Hopkins University Press, 1975, pp 147-165 5. Usdin E (Ed): Neuropharmacology of Monoamines and their Regulatory Enzymes. New York, Raven Press, 1974 6. Snyder SH: The dopamine hypothesis of schizophrenia: Focus on the dopamine receptor. Am J Psychiatry 133:197-202,
1976
SPECIAL EDITORIAL
Radiation Risks of Mammography IN THIS DECADE of increased public awareness of environmental hazards, it is hardly surprising that extensive publicity be given to statements on the potential carcinogenic effects of widely-used x-ray examinations. Such adverse publicity has recently been circulated concerning mammography, publicity that unfortunately contains many inaccuracies and gross overstatements. Mammography is a valuable diagnostic tool for detection of breast cancer. When used in conjunction with physical examination, the diagnosis of carcinoma can be made with a high degree of accuracy, especially in women over age 50.1-3 Mammography is particularly useful in discovering early breast cancer. Fully a third of the early cancer found among asymptomatic women is found by mammography alone;4'5 this applies equally to women above and below age 50.6 Despite these proved advantages, the full bene-
fits and potential risks of mammography are not fully known. For these reasons and others the American Cancer Society (ACS) and the National Cancer Institute (NCI) jointly are sponsoring a nationwide breast cancer detection project designed to screen 270,000 asymptomatic women. It is hoped that this project will result in a determination of the proper role that mammography should play in detection of early breast cancer. Specifically, information should be forthcoming on (1) the optimal age for the initial mammogram, (2) the proper frequency of screening mammograms and (3) whether or not there are significant long-term radiation risks. There is a wealth of information on the carcinogenic effect of large doses of x-rays (100 rads or more). However, despite numerous controlled animal experiments and extensive epidemiologic analyses of human cancer, remarkably little is known of the sequelae of low doses of radiation, especially in the range in which mammography now functions (0.5 to 5 rads surface dose, breast tissue dose substantially lower). In fact, there is no hard evidence of x-ray induction of cancer in any adult human being with radiation doses less than 50 rads;7 specifically for the breast this limit appears to be 90 rads.8-11 In order to apply the data from high-dose studies to the much lower doses used in diagnostic radiology, most radiobiologists construct a doseresponse curve and extrapolate linearly back toward zero, assuming that there is no threshold dose below which carcinogenic effects are absent. However, this type of approach is misleading, especially since the calculations result in highly specific conclusions having the ring of scientific accuracy. In fact, such analyses are based on assumptions that have never been proved, and about which there is considerable disagreement.'2-14 Conclusive evidence does not exist for either a linear dose-response curve or lack of a threshold dose.12-'5 Therefore, even the most impressive statistical analysis that leads to these assumptions must be considered inaccurate, with the probability that this inaccuracy will result in significant overestimations of risk.15-16 The recent analyses that have received national press coverage attempted to evaluate the benefits and cumulative radiation risk of multiple mammographic examinations in asymptomatic women. These analyses by Bailar16 and Breslow17 were based on the best available study (the HIP [Health Insurance Plan of Greater New York] study) of THE WESTERN JOURNAL OF MEDICINE
493
EDITORIALS
screening mammography, begun in 1963, which showed a substantial reduction in breast cancer mortality only for women over age 50.1,5 Breslow used the HIP study to conclude that screening mammography under age 50 was not recommended, but that the benefits outweighed the risks in women over 50. Neither Breslow nor Bailar attacked the advisability of single mammographic examinations, probably since the resultant radiation doses were so small. However, both analyses suffer from two serious weaknesses: (1) the risk analysis was based on the unproved assumptions of a linear dose-response curve and lack of threshold dose and (2) no allowance was made for the improvements in mammographic equipment, technique and knowledge that have accrued in the greater than ten-year interval since the HIP study mammograms were taken. These improvements are illustrated by preliminary data from the breast cancer detection project, which show that a third of the breast cancer so far detected has been in women under age 50, and that 45 percent of this cancer was detected by mammography alone.6 Unfortunately, the effects of the Bailar and Breslow analyses have been quite far-reaching, almost certainly due to extensive and misleading lay press coverage. By elevating what are in fact unproved estimates of risk to the status of scientific acceptance, the press has unduly alarmed the public about radiation hazards of mammography. This error is further compounded by grossly overstating the conclusions to apply to all mammography situations rather than only to multiple screening examinations in women under age 50. Headlines such as "Breast Cancer: Does One Exam Cause a Tumor?"'8 are to be deplored. One adverse effect of this publicity has been a substantial reduction (as much as 30 to 40 percent) in mammographic examinations across the country, not only among asymptomatic women above and below age 50 but also in women with signs and symptoms suggesting the presence of breast cancer. Of the many women who are now avoiding mammography, some most probably have early cancer detectable only by the examination they have been misled to refuse. This will inevitably result in isolated individual tragedies. More disturbing is the recent decision of the ACS and NCI to recommend against mammography for asymptomatic women aged 35 to 50 in their nationwide screening centers. This amounts to abandonment of a portion of the breast cancer 494
DECEMBER 1976 * 125 * 6
detection project, a step backwards which will result in loss of the very benefit-versus-risk data that promise to indicate accurately the extent to which screening mammography is advisable. It is ironic that the ACS-NCI decision is based on the same inadequate and probably inaccurate data that helped prompt the breast cancer detection project in the first place; and it is unfortunate that the ACS and NCI seem to have based their decision on public reaction to misleading and overstated media reports rather than on any conclusive scientific evidence. Now is the time to put the situation straight. To that end I offer the following suggestions. (1) Mammography should remain an integral part of the evaluation of women who have symptoms or physical findings suggestive of breast cancer, regardless of age. (2) Screening mammography in asymptomatic women over 50 should continue to be done at regular intervals since even now there is general agreement that its benefits outweigh the risks. (3) The ACS and NCI should reverse their decision and encourage screening mammography in asymptomatic women in the 35 to 50 age group. The data to be compiled from the nationwide breast cancer detection project currently offer the best hope for determining the proper role for mammography for women of all ages. Let us not abandon this hope because of admittedly insufficient risk evidence, especially since preliminary findings of the screening project indicate substantial benefits for women under 50. (4) Mammography should be carried out at the lowest possible radiation dose consistent with current diagnostic accuracy. Radiologists should strongly consider using high-filtration xeroradiographic techniques or the even lower dose screenfilm systems that have recently been marketed. Mammography done in this fashion produces a fourth or less radiation than assumed in the calculations of Bailar, and even allowing for his inaccurate analytic methods would shift his conclusions clearly in favor of mammography. All involved in the current mammography controversy agree that we know too little about radiation risks to draw firm conclusions. Some, relying heavily on the "best" evidence now available, would limit the scope of mammography until more conclusive data can be generated. I must remind them, however, that no animal experiments and no retrospective statistical analyses can produce data any more meaningful than those which are available now. Rather, we must design
-EDITORIALS
prospective clinical studies to determine benefits and risks as accurately as possible. Such studies, of course, should require informed consent of all participants. The most promising attempt to date has been the joint ACS-NCI project. Mammography is already known to be beneficial for symptomatic patients of all ages and for the screening of asymptomatic women over 50. Let us now find out whether this also applies to the screening of women under 50 by proceeding with the breast cancer detection project without alteration or delay. EDWARD A. SICKLES, MD Chief, Mammography Section Department of Radiology University of California, San Francisco
REFERENCES 1. Strax P, Venet L, Shapiro S: Value of mammography in reduction of mortality from breast cancer in mass screening. Am J Ronetgenol 117:686-689, 1973 2. Stark AM, Way S: The screening of well women for the early detection of breast cancer using clinical examination with thermography and mammography. Cancer 33:1671-1679, 1974 3. Sadowsky NL, Kalisher L, White G, et al: Radiologic detection of breast cancer-Review and recommendations. N Engl J Med 294:370-373, 1976
EDITOR'S NOTE: The above editorial was sent to Lester Breslow, MD, for comment. Dr. Breslow's views are presented below. A reply from Dr. Sickles will appear in the Correspondence section next month.
Radiation Risks of Mammography: Another View IT IS PROBABLY TRUE that recent and unfortunately sometimes misleading publicity has created some undue alarm about the risks of mammography. Matters are not set straight, however, by statements such as that of Sickles. He touches mainly on two points. One point advanced by Sickles can be represented by quoting from his editorial: ". . . potential risks of mammography are not fully known." most radiobiologists construct a doseresponse curve and extrapolate linearly back toward zero, assuming that there is no threshold below which carcinogenic effects are absent." ". . . such analyses are based on assumptions that have never been proved, and about which there is considerable disagreement. Conclusive
4. Wolfe JN: Analysis of 462 breast carcinomas. Am J Roentgenol 121:846-853, 1974 5. Strax P: Control of breast cancer through mass screening. JAMA 235:1600-1602, 1976 6. Preliminary unedited (current) statistics, Breast Cancer Detection Demonstration Project, Bethesda, Md, Jul 19, 1976 7. Margulis AR: The lesions of radiobiology for diagnostic radiology. Caldwell Lecture, 1972. Am J Roentgenol 117:741756, 1973 8. MacKenzie I: Breast cancer following multiple fluoroscopies. Br J Cancer 19:1-8, 1965 9. Wanebo CK, Johnson KG, Sato K, et al: Breast cancer after exposure to the atomic bombings of Hiroshima and Nagasaki. N Engl J Med 279:667-671, 1968 10. Myrden JA, Hiltz JE: Breast cancer following multiple fluoroscopies during artificial pneumothorax treatment of pulmonary tuberculosis. Canad Med Assoc J 100:1032-1034, 1969 11. Mettler FA Jr, Hempelmann LH, Dutton AM, et al: Breast neoplasms in women treated with x-rays for acute postpartum mastititis-A pilot study. J Nat Cancer lnst 43:803-811, 1969 12. Rossi HH, Kellerer AM: Radiation carcinogenesis at low doses. Science 175:200-202, 1972 13. Mole RH: Ionizing radiation as a carcinogen: Practical questions and academic pursuits. Br J Radiol 48:157-169, 1975 14. Morgan KZ: Reducing medical exposure to ionizing radiation. J Am Industr Hyg Assoc 36:358-368, 1975 15. National Council on Radiation Protection and Measurements: Review of the Current State of Radiation Protection Philosophy. NCPR Report No. 43. Washington, National Council on Radiaticn Protection, 1975 16. Bailar JC III: Mammography: A contrary view. Ann Intern Med 84:77-84, 1976 17. Breslow L: Unpublished data, released Jul 15, 1976 18. San Francisco Chronicle: Jul 29, 1976, p 17
evidence does not exist for either a linear doseresponse curve or lack of a threshold dose." In our report to the National Cancer Institute of 15 July 1976,1 we stated: "The basis for believing that mammography may induce breast cancer lies in a series of studies indicating that exposure of the breast to radiation can cause breast cancer. These studies show that women (a) exposed to radiation in the Japan atomic bomb explosion;2-4 (b) treated by radiation for benign breast disease;5 or (c) subjected to repeated x-ray fluoroscopy of the chest in connection with treatment for tuberculosis,6-'0 all suffered a significantly higher incidence of breast cancer in later years than did comparable groups of women considered as controls. Although the amount of radiation exposure in these series of women was many times greater than that encountered in mammography, a National Academy of Sciences review indicated (and we concur) that one must assume a linear dose-response relationship on the basis of present evidence and in the absence of any clear information to the contrary." This means that there is no absolutely safe dose and that, in the case of breast cancer induced by x-rays, the number of cases resulting from the exposure will be simply proportional to THE WESTERN JOURNAL OF MEDICINE
495
