1575
place them at increased risk of heart disease despite a low risk lifestyle. The UK has yet to promote a national strategy for cholesterol screening; potential options include selective screening based on a positive family history, opportunistic screening guided by an assessment of all risk factors, and universal screening of young men. Is there a convincing case for including cholesterol measurement in child health that
surveillance? A valid
screening
programme should detect
an
important disease about which there is adequate understanding of the natural history, and for which there is effective prevention or therapy. There is no dispute that coronary heart disease is important and that it probably has its origins in childhood, if not earlier.4,5 Raised cholesterol is an established risk factor; trials of serum cholesterol reduction in adults show a decrease in coronary heart disease incidence and in mortality from this condition.6 Age-related population data for blood lipid levels7,8 are available and longitudinal studies are beginning to define the nature of tracking of high levels into adult life.3 It is claimed that 25-50% of adult low-densitylipoprotein-cholesterol variability can be attributed to childhood concentrations. A programme based on 6500 3-18-year-olds living in suburban Ohio2 found that 20% had capillary cholesterol concentrations above 4-8 mmoll, a value previously suggested as the ninetieth centile for this age group. Subsequent fasting blood lipid analysis in 500 high rankers showed that 93% still had high cholesterol concentrations.9 Others have shown substantial variability within individuals, and multiple measurements with reliable techniques are essential before assigning a child to a high-risk category. Several studies report that only half the high rankers would have been detected if screening had been limited to children with a positive family history. 2,10 Before family history is dismissed as a guide to children who merit cholesterol measurement we need more information about the phenotypic and genotypic classification of hyperlipidaemia discovered by population screening. Are hypercholesterolaemic children with apparently healthy parents really at risk, or is it more relevant to ask whether either parent smokes? Family history will
surely become a more reliable guide as strategies for assessing risk factors and conducting cholesterol screening in the adult population evolve. There is no justification for inadequately structured screening generated merely by the availability of equipment and divorced from the support of diagnostic and counselling skills. There is also scant evidence that allocating children who do not have a positive family history to an apparent higher risk category serves as a stimulus to improved healthrelated lifestyle. Any benefit claimed has to be judged against that which can be achieved by public health strategies supported by statutory measures. Allocating ill-defined risk to a child is a threat to the family, and may well have deleterious effects on harmony and
health. Diabetic teenagers have already taught us that emphasising potential health hazards does little to generate compliance. Self-discipline and sustained motivation are fragile qualities in adolescence, and it is unlikely that knowledge of a raised cholesterol concentration will be a reforming influence. In health systems that must decide priorities, risk factor detection and management has to be a staged process, with those at greater risk given preference.6Resources are better directed at children in whom a careful family history suggests a risk of familial hypercholesterolaemia or allied disorders, and in whom there is a clear case for long-term dietary supervision and possible drug therapy. The challenge is to define risk status more precisely, possibly by use of apolipoprotein B measurement," and to develop treatment strategies that are effective and safe in young people. 1. Office of
Population Censuses registrations. OPCS Monitor,
and Surveys. Deaths by cause: 1987 1988 (Sept 17). 2. Garcia RE, Moodie DS. Routine cholesterol surveillance in childhood. Pediatrics 1989; 84: 751-55. 3. Lauer RM, Lee J, Clarke WR. Factors affecting the relationship between childhood and adult cholesterol levels: the Muscatine study. Pediatrics
1988; 82: 309-18. 4. Barker DJP, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet 1989; ii: 577-80. 5. Barker D. The intrauterine origins of cardiovascular and obstructive lung disease in adult life. J R Coll Physicians Lond 1991; 25: 129-33. 6. Lewis B, Rose G. Prevention of coronary heart disease: putting theory into practice. J R Coil Physicians Lond 1991; 25: 21-26. 7. Rifkind B, Sega P. Lipid Research Clinics Program reference values for hyperlipidemia and hypolipidemia. JAMA 1983; 250: 1869-72. 8. Srinivasan S, Frerichs R, Weber L, Berenson G. Serum lipoprotein profile in children from a biracial community: the Bogalusa Heart Study. Circulation 1976; 54: 309-18. 9. Garcia RE, Moodie DS. Lipoprotein profiles in hypercholesterolemic children. AM J Dis Child 1990; 145: 147-50. 10. Dennison BA, Kikuchi DA, Srinivasan SR, Webber LS, Berenson GS. Parental history of cardiovascular disease as an indication for screening for lipoprotein abnormalities in children. J Pediatr 1989; 115: 186-94. 11. Sniderman A, Silberberg J. Is it time to measure apolipoprotein B? Arteriosclerosis 1990; 10: 665-67.
Breast
cancer
screening
in
women
under 50 Recent debate about the optimum treatment for breast cancer1,2 must have alarmed many women who previously had thought that early diagnosis and curative resection were the twin planks on which effective management rested. Their fears will not have been allayed by a front page story in the Sunday Times of June 2 under the headline "Breast scans boost risk of cancer death". The report described interviews with Dr Cornelia Baines (Department of Preventive Medicine and Biostatistics, University of Toronto, Canada) and Prof Anthony Miller (currently at the World Health Organisation, Geneva), the senior investigators of the Canadian National Breast Screening Study. These researchers found that women aged 40-49 years who had undergone mammography and physical examination had a higher death rate from breast cancer than women who had undergone only a single physical breast examination.
1576
In this age group, the Canadian study set out to find "what reduction in breast cancer mortality could be observed with combined annual screening of the and examination [mammography physical care to normal community breasts] compared [yearly self-examination reminders] following a single physical examination of the breasts". 3,4 The study included 50 000 volunteers and was conducted between 1980 and 1988. The study protocol and the reliability of the data have already been fiercely criticised.5 In at least the first 2 years of the study, over 50% of mammograms were inadequate; only in the last 2 years of the trial was image quality technically acceptable in more than 70% of screenings. Modem radiographic equipment was not routinely available to participating centres, and the equipment used was not standardised. In addition, there was no coordinated training programme for either radiologists or radiographers. These discrepancies led two external advisers to resign. Kopans,5 who is a co-author of earlier reports of the Canadian study,4wrote that because of uncertainty as to whether disease severity was equally distributed between the groups of women "the results of this trial will always be suspect". That the Canadian study has no bearing on the UK screening programme, which involves mammography in women aged 50-64 years only and has a centralised organisation with recognised training courses and quality assurance standards, was not made clear in the newspaper article. The latest Canadian results, which have not been published, were discussed at the Second International Cambridge Conference on Breast Cancer Screening in April. Concerns about group comparability because of poor randomisation seem to have been unfounded since there were equal numbers of non-breast-cancer deaths (157) in the screened and control groups. The 44 deaths from breast cancer in the screened group vs 29 in the control group translates into a 52% increase in breast cancer mortality among those screened. Poor quality mammography may lead to a poor quality screening programme but this should not in itself lead to increases in mortality in the study group. Although these results are the first to show a statistically significant increase in breast cancer mortality in a population who underwent screening mammography, other published studies have shown non-significant trends in the same direction, ranging from 3 to 29% The death rates in the with 6-8 years of follow-up.&-9 Canadian study may fall with time since a longer period of follow-up seems to diminish the adverse effect of mammography in this age group (I. Andersson, Second International Cambridge Conference on Breast Cancer Screening, April, 1991).10,ll Why does mortality increase during the initial period of follow-up? One explanation may be the type of treatment offered to women with mammographically detected breast cancers-usually a combination of surgery and radiotherapy. Thus, when many of these trials began in the early 1980s,
adjuvant systemic therapy was not given routinely. Systemic therapy soon after or coincident with surgery for premenopausal women with breast cancer may be the important variable that is missing from the treatment associated with these screening studies. It is possible that systemic therapy is especially important in the younger age group. The implications of these results remain uncertain. There is no evidence to support introduction of
service mammography for women under 50, and some may argue that there should be a moratorium on all mammography for symptom-free women in this age group outside randomised controlled trials.12 In the UK, some private sector schemes are actively recruiting younger women into mammography programmes. The Canadian data and the results of a review of all Swedish screening trials due to be published at the end of this year will have a bearing on a new UK trial that aims to randomise individually 200 000 women aged 40-41 years to assess the value of yearly mammography on breast cancer mortality. One-third of women in the UK trial will be in the study group while two-thirds will act as controls. 3-3 deaths per 1000 women are expected during the 10-year trial. The study group size is sufficient to give an 80% power of detecting a 20% reduction in mortality over a 10-year period-to 2-6 per 1000 women-at the 5% significance level. Recruitment at pilot centres in Guildford and Edinburgh has already begun; it may be necessary to revise the protocol to include recommendations for treatment before extending the trial to other centres. 1. Fentiman IS, Mansel RE. The axilla: not a no-go zone. Lancet 1991; 337: 221-23. 2. Badwe RA, Gregory WM, Chauddry MA, et al. Timing of surgery during menstrual cycle and survival of premenopausal women with operable breast cancer. Lancet 1991; 337: 1261-64. 3. Baines CJ. Evaluation of mammography and physical examination as independent screening modalities in the Canadian National Breast Screening Study. In: Ziant G, ed. Practical modalities of an efficient screening for breast cancer in the European community. Amsterdam: Elsevier, 1989: 3-9. 4. Baines CJ, Miller AB, Kopans DB, et al. Canadian National Breast Screening study: assessment of technical quality by external review. AJR 1990; 155: 743-47. 5. Kopans DB. The Canadian Screening Program: a different perspective. 6.
AJR 1990; 155: 748-49. Shapiro S, Venet N, Strax P, Venet L, Roeser R. Ten to fourteen year effect of breast cancer screening on mortality. J Natl Cancer Inst 1982;
69: 349-55. 7. Tabar L, Gad A, Homberg LH, et al. Reduction in mortality from breast cancer after mass screening with mammography. Lancet 1985; i: 829-32. 8. Verbeek ALM, Hendriks JHCL, Holland R, Mravunac M, Sturmans F.
Mammographic screening and breast cancer mortality: age-specific effects in Nijmegen project 1975-82. Lancet 1985; i: 865-66. 9. Andersson I, Aspegren K, Janzon L, et al. Mammographic screening and mortality from breast cancer: the Malmo mammographic screening trial. Br Med J 1988; 297: 943-48. 10. Shapiro S, Venet W, Strax P, Venet L. Periodic screening for breast cancer: the Health Insurance Plan Project and its sequelae. Baltimore: Johns Hopkins University Press, 1988: 1963-86. 11. Tabar L, Fagerberg F, Duffy SW, Day NE. The Swedish Two Counties Trial of Mammographic Screening for Breast Cancer: recent results and calculation of benefit. J Epidemiol Community Health 1989; 43: 107-14. 12.
of Radiologists and National Radiological Protection Board. Patient dose reduction in diagnostic radiology. Documents of the NRPB, vol 1. London: HM Stationery Office, 1990.
Royal College
place them at increased risk of heart disease despite a low risk lifestyle. The UK has yet to promote a national strategy for cholesterol screening; potential options include selective screening based on a positive family history, opportunistic screening guided by an assessment of all risk factors, and universal screening of young men. Is there a convincing case for including cholesterol measurement in child health that
surveillance? A valid
screening
programme should detect
an
important disease about which there is adequate understanding of the natural history, and for which there is effective prevention or therapy. There is no dispute that coronary heart disease is important and that it probably has its origins in childhood, if not earlier.4,5 Raised cholesterol is an established risk factor; trials of serum cholesterol reduction in adults show a decrease in coronary heart disease incidence and in mortality from this condition.6 Age-related population data for blood lipid levels7,8 are available and longitudinal studies are beginning to define the nature of tracking of high levels into adult life.3 It is claimed that 25-50% of adult low-densitylipoprotein-cholesterol variability can be attributed to childhood concentrations. A programme based on 6500 3-18-year-olds living in suburban Ohio2 found that 20% had capillary cholesterol concentrations above 4-8 mmoll, a value previously suggested as the ninetieth centile for this age group. Subsequent fasting blood lipid analysis in 500 high rankers showed that 93% still had high cholesterol concentrations.9 Others have shown substantial variability within individuals, and multiple measurements with reliable techniques are essential before assigning a child to a high-risk category. Several studies report that only half the high rankers would have been detected if screening had been limited to children with a positive family history. 2,10 Before family history is dismissed as a guide to children who merit cholesterol measurement we need more information about the phenotypic and genotypic classification of hyperlipidaemia discovered by population screening. Are hypercholesterolaemic children with apparently healthy parents really at risk, or is it more relevant to ask whether either parent smokes? Family history will
surely become a more reliable guide as strategies for assessing risk factors and conducting cholesterol screening in the adult population evolve. There is no justification for inadequately structured screening generated merely by the availability of equipment and divorced from the support of diagnostic and counselling skills. There is also scant evidence that allocating children who do not have a positive family history to an apparent higher risk category serves as a stimulus to improved healthrelated lifestyle. Any benefit claimed has to be judged against that which can be achieved by public health strategies supported by statutory measures. Allocating ill-defined risk to a child is a threat to the family, and may well have deleterious effects on harmony and
health. Diabetic teenagers have already taught us that emphasising potential health hazards does little to generate compliance. Self-discipline and sustained motivation are fragile qualities in adolescence, and it is unlikely that knowledge of a raised cholesterol concentration will be a reforming influence. In health systems that must decide priorities, risk factor detection and management has to be a staged process, with those at greater risk given preference.6Resources are better directed at children in whom a careful family history suggests a risk of familial hypercholesterolaemia or allied disorders, and in whom there is a clear case for long-term dietary supervision and possible drug therapy. The challenge is to define risk status more precisely, possibly by use of apolipoprotein B measurement," and to develop treatment strategies that are effective and safe in young people. 1. Office of
Population Censuses registrations. OPCS Monitor,
and Surveys. Deaths by cause: 1987 1988 (Sept 17). 2. Garcia RE, Moodie DS. Routine cholesterol surveillance in childhood. Pediatrics 1989; 84: 751-55. 3. Lauer RM, Lee J, Clarke WR. Factors affecting the relationship between childhood and adult cholesterol levels: the Muscatine study. Pediatrics
1988; 82: 309-18. 4. Barker DJP, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet 1989; ii: 577-80. 5. Barker D. The intrauterine origins of cardiovascular and obstructive lung disease in adult life. J R Coll Physicians Lond 1991; 25: 129-33. 6. Lewis B, Rose G. Prevention of coronary heart disease: putting theory into practice. J R Coil Physicians Lond 1991; 25: 21-26. 7. Rifkind B, Sega P. Lipid Research Clinics Program reference values for hyperlipidemia and hypolipidemia. JAMA 1983; 250: 1869-72. 8. Srinivasan S, Frerichs R, Weber L, Berenson G. Serum lipoprotein profile in children from a biracial community: the Bogalusa Heart Study. Circulation 1976; 54: 309-18. 9. Garcia RE, Moodie DS. Lipoprotein profiles in hypercholesterolemic children. AM J Dis Child 1990; 145: 147-50. 10. Dennison BA, Kikuchi DA, Srinivasan SR, Webber LS, Berenson GS. Parental history of cardiovascular disease as an indication for screening for lipoprotein abnormalities in children. J Pediatr 1989; 115: 186-94. 11. Sniderman A, Silberberg J. Is it time to measure apolipoprotein B? Arteriosclerosis 1990; 10: 665-67.
Breast
cancer
screening
in
women
under 50 Recent debate about the optimum treatment for breast cancer1,2 must have alarmed many women who previously had thought that early diagnosis and curative resection were the twin planks on which effective management rested. Their fears will not have been allayed by a front page story in the Sunday Times of June 2 under the headline "Breast scans boost risk of cancer death". The report described interviews with Dr Cornelia Baines (Department of Preventive Medicine and Biostatistics, University of Toronto, Canada) and Prof Anthony Miller (currently at the World Health Organisation, Geneva), the senior investigators of the Canadian National Breast Screening Study. These researchers found that women aged 40-49 years who had undergone mammography and physical examination had a higher death rate from breast cancer than women who had undergone only a single physical breast examination.
1576
In this age group, the Canadian study set out to find "what reduction in breast cancer mortality could be observed with combined annual screening of the and examination [mammography physical care to normal community breasts] compared [yearly self-examination reminders] following a single physical examination of the breasts". 3,4 The study included 50 000 volunteers and was conducted between 1980 and 1988. The study protocol and the reliability of the data have already been fiercely criticised.5 In at least the first 2 years of the study, over 50% of mammograms were inadequate; only in the last 2 years of the trial was image quality technically acceptable in more than 70% of screenings. Modem radiographic equipment was not routinely available to participating centres, and the equipment used was not standardised. In addition, there was no coordinated training programme for either radiologists or radiographers. These discrepancies led two external advisers to resign. Kopans,5 who is a co-author of earlier reports of the Canadian study,4wrote that because of uncertainty as to whether disease severity was equally distributed between the groups of women "the results of this trial will always be suspect". That the Canadian study has no bearing on the UK screening programme, which involves mammography in women aged 50-64 years only and has a centralised organisation with recognised training courses and quality assurance standards, was not made clear in the newspaper article. The latest Canadian results, which have not been published, were discussed at the Second International Cambridge Conference on Breast Cancer Screening in April. Concerns about group comparability because of poor randomisation seem to have been unfounded since there were equal numbers of non-breast-cancer deaths (157) in the screened and control groups. The 44 deaths from breast cancer in the screened group vs 29 in the control group translates into a 52% increase in breast cancer mortality among those screened. Poor quality mammography may lead to a poor quality screening programme but this should not in itself lead to increases in mortality in the study group. Although these results are the first to show a statistically significant increase in breast cancer mortality in a population who underwent screening mammography, other published studies have shown non-significant trends in the same direction, ranging from 3 to 29% The death rates in the with 6-8 years of follow-up.&-9 Canadian study may fall with time since a longer period of follow-up seems to diminish the adverse effect of mammography in this age group (I. Andersson, Second International Cambridge Conference on Breast Cancer Screening, April, 1991).10,ll Why does mortality increase during the initial period of follow-up? One explanation may be the type of treatment offered to women with mammographically detected breast cancers-usually a combination of surgery and radiotherapy. Thus, when many of these trials began in the early 1980s,
adjuvant systemic therapy was not given routinely. Systemic therapy soon after or coincident with surgery for premenopausal women with breast cancer may be the important variable that is missing from the treatment associated with these screening studies. It is possible that systemic therapy is especially important in the younger age group. The implications of these results remain uncertain. There is no evidence to support introduction of
service mammography for women under 50, and some may argue that there should be a moratorium on all mammography for symptom-free women in this age group outside randomised controlled trials.12 In the UK, some private sector schemes are actively recruiting younger women into mammography programmes. The Canadian data and the results of a review of all Swedish screening trials due to be published at the end of this year will have a bearing on a new UK trial that aims to randomise individually 200 000 women aged 40-41 years to assess the value of yearly mammography on breast cancer mortality. One-third of women in the UK trial will be in the study group while two-thirds will act as controls. 3-3 deaths per 1000 women are expected during the 10-year trial. The study group size is sufficient to give an 80% power of detecting a 20% reduction in mortality over a 10-year period-to 2-6 per 1000 women-at the 5% significance level. Recruitment at pilot centres in Guildford and Edinburgh has already begun; it may be necessary to revise the protocol to include recommendations for treatment before extending the trial to other centres. 1. Fentiman IS, Mansel RE. The axilla: not a no-go zone. Lancet 1991; 337: 221-23. 2. Badwe RA, Gregory WM, Chauddry MA, et al. Timing of surgery during menstrual cycle and survival of premenopausal women with operable breast cancer. Lancet 1991; 337: 1261-64. 3. Baines CJ. Evaluation of mammography and physical examination as independent screening modalities in the Canadian National Breast Screening Study. In: Ziant G, ed. Practical modalities of an efficient screening for breast cancer in the European community. Amsterdam: Elsevier, 1989: 3-9. 4. Baines CJ, Miller AB, Kopans DB, et al. Canadian National Breast Screening study: assessment of technical quality by external review. AJR 1990; 155: 743-47. 5. Kopans DB. The Canadian Screening Program: a different perspective. 6.
AJR 1990; 155: 748-49. Shapiro S, Venet N, Strax P, Venet L, Roeser R. Ten to fourteen year effect of breast cancer screening on mortality. J Natl Cancer Inst 1982;
69: 349-55. 7. Tabar L, Gad A, Homberg LH, et al. Reduction in mortality from breast cancer after mass screening with mammography. Lancet 1985; i: 829-32. 8. Verbeek ALM, Hendriks JHCL, Holland R, Mravunac M, Sturmans F.
Mammographic screening and breast cancer mortality: age-specific effects in Nijmegen project 1975-82. Lancet 1985; i: 865-66. 9. Andersson I, Aspegren K, Janzon L, et al. Mammographic screening and mortality from breast cancer: the Malmo mammographic screening trial. Br Med J 1988; 297: 943-48. 10. Shapiro S, Venet W, Strax P, Venet L. Periodic screening for breast cancer: the Health Insurance Plan Project and its sequelae. Baltimore: Johns Hopkins University Press, 1988: 1963-86. 11. Tabar L, Fagerberg F, Duffy SW, Day NE. The Swedish Two Counties Trial of Mammographic Screening for Breast Cancer: recent results and calculation of benefit. J Epidemiol Community Health 1989; 43: 107-14. 12.
of Radiologists and National Radiological Protection Board. Patient dose reduction in diagnostic radiology. Documents of the NRPB, vol 1. London: HM Stationery Office, 1990.
Royal College
