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Breast screening programme: should the interval between tests depend on age?
THE LANCET
5
polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet 1995; 4: 337–40. Eccles DM, Vanderluijt R, Breukel C, et al. Hereditary desmoid disease due to a frameshift mutation of codon-1924 of the APC gene. Am J Hum Genet 1996; 59: 1193–201.
ICRF Colorectal Cancer Unit, St Mark’s Hospital, Northwick Park, Harrow; Department of Haematology and Oncology, Great Ormond Street Hospital for Children, London; and South Thames Regional Genetics Centre (East), Guy’s Hospital, London SE1 9RT, UK (S V
screening programme can offer then a different scheduling of visits might produce a greater return on the same investment. 1
2
3
Breast screening programme: should the interval between tests depend on age? Anthony G Threlfall, Ciaran B J Woodman, Pat Prior
The NHS breast screening programme was introduced in 1988 following the report of a committee, which recommended that women aged 50–64 years should be screened every 3 years, but also concluded that for different age groups the optimum screening interval may not be the same and that this should have a high research priority.1 We now describe the frequency with which cancers present between screening appointments (interval cancers) in relation to age at time of screening. Interval cancers provide an early indication of the appropriateness of a screening interval and recent reports show that the overall occurrence of these cancers in the screening programme is substantially higher than predicted, especially in the third year after screening.2,3 The occurrence of interval cancers in 79 918 women screened with single-view mammography at three screening units in northwestern England between 1988 and March 31, 1991, is shown in the table. Interval cancers are presented for each year following a negative screen in women above and below the age of 60 at the time of screening. The number of cancers expected to occur in these women, assuming they had not been screened, was estimated by extrapolating from an age-period model,4 allowing for ageing of the cohort and a small general increase in incidence over a calendar year. The relative risk (observed interval cancers/expected number of cancers in the absence of screening) of a breast cancer occurring within 3 years of a negative screen was 0·523 in women aged 50–59 but was 0·317 in the older age group (x2test; p<0·001). Interval cancer targets for the NHS breast screening programme are based on the results of the Swedish Two County Trial, because this large randomised trial achieved a 31% reduction in mortality from breast cancer. In northwestern England interval cancer rates are unacceptably high in younger women but are substantially lower in older women, and only in this latter age group are similar to those achieved in the Swedish Two County Trial.5 If our findings are replicated elsewhere and financial considerations continue to limit the number of tests which the NHS breast Time from negative 1st screen (yr)
<1 1–2 2–3 0–3
Age at first screening (yr) 50–59 (n=53 643)
60–64 (n=26 275)
O
E
O/E
O
E
O/E
34 52 79 165
101·1 105·3 109·0 315·4
0·336 0·494 0·725 0·523
9 13 37 59
59·7 62·1 64·5 186·3
0·151 0·209 0·574 0·317
O=observed number of interval cancers. E=expected numbers of cancers predicted by the age-period model for unscreened women.
Observed (O) and expected (E) number of cancers in relation to age and time from screening
472
4
5
Forrest P. Breast cancer screening: report to the health ministers of England, Scotland and Northern Ireland. London: HM Stationery Office, 1986. Woodman CBJ, Threlfall AG, Boggis CRM, Prior P. Is the three year breast screening interval too long? Occurrence of interval cancers in the NHS breast screening programme’s north western region. BMJ 1995; 310: 224–26. Day N, McCann J, Camilleri-Ferrante C, et al. Monitoring interval cancers in breast screening programmes: the East Anglian experience. J Med Screen 1995; 2: 180–85. Prior P, Wilson S, Woodman CBJ, Threlfall AG. The reliability of underlying incidence rates for estimating the effect and efficiency of screening for breast cancer. J Med Screen 1996; 3: 119–22. Tabar L, Faberberg G, Day NE, Holmberg L. What is the optimum interval between mammographic screening examinations? An analysis based on the latest results of the Swedish two-county breast cancer screening trial. Br J Cancer 1987; 55: 547–51.
Centre for Cancer Epidemiology, Christie Hospital NHS Trust, Withington, Manchester M20 4QL, UK (A G Threlfall)
Infant mortality and the incidence of inflammatory bowel disease Scott M Montgomery, Roy E Pounder, Andrew J Wakefield
The last half of this century has seen a rising incidence of inflammatory bowel disease (IBD) in developed countries. Gent et al suggested that the increasing incidence of Crohn’s disease could be due to delayed exposure to enteric infections.1 We investigated the relation between infant mortality (an indicator of social circumstances and infections in early life) and incidence of IBD. To avoid bias due to changing diagnostic criteria, we used data from the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD), which prospectively identified newly diagnosed cases of IBD with a standard protocol between October, 1991 and September, 1993.2 Published EC-IBD data provided estimates of the incidence of Crohn’s disease and ulcerative colitis in 13 countries in the age range 15–44 years.2 An average was calculated when more than one incidence rate per country was reported. The infant mortality rates in each country for the years 1960–80 were used to calculate an average rate for the period when most of these patients were infants.3–5 The figure shows the relation between infant mortality rate in 1960–80 and the 1991–93 incidence of Crohn’s disease in 15–44 year olds in 13 countries. A lower infant mortality rate is significantly correlated with a higher incidence of Crohn’s disease (Pearson correlation coefficient =–0·71, p=0·006). A similar but weaker relation was found for ulcerative colitis (Pearson correlation coefficient=–0·53, p=0·062; data not shown). The data suggest a threshold effect: once infant mortality drops below a certain level, the incidence of IBD increases at a steeper gradient with decreasing infant mortality. Portugal, which had a relatively high infant mortality, is well below the hypothesised threshold, so its exclusion from the analysis provides information about the relation in countries above the threshold. The Pearson correlation coefficient for the relation of infant mortality with incidence of Crohn’s disease among these 12 countries is –0·84 (p=0·001). These observations may provide a clue to explain the rise in incidence of IBD in recent years, and also the apparent absence of IBD in developing countries where infant mortality is high. A factor associated with lower infant mortality may itself be a risk for developing IBD, such as
Vol 349 • February 15, 1997
5
polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet 1995; 4: 337–40. Eccles DM, Vanderluijt R, Breukel C, et al. Hereditary desmoid disease due to a frameshift mutation of codon-1924 of the APC gene. Am J Hum Genet 1996; 59: 1193–201.
ICRF Colorectal Cancer Unit, St Mark’s Hospital, Northwick Park, Harrow; Department of Haematology and Oncology, Great Ormond Street Hospital for Children, London; and South Thames Regional Genetics Centre (East), Guy’s Hospital, London SE1 9RT, UK (S V
screening programme can offer then a different scheduling of visits might produce a greater return on the same investment. 1
2
3
Breast screening programme: should the interval between tests depend on age? Anthony G Threlfall, Ciaran B J Woodman, Pat Prior
The NHS breast screening programme was introduced in 1988 following the report of a committee, which recommended that women aged 50–64 years should be screened every 3 years, but also concluded that for different age groups the optimum screening interval may not be the same and that this should have a high research priority.1 We now describe the frequency with which cancers present between screening appointments (interval cancers) in relation to age at time of screening. Interval cancers provide an early indication of the appropriateness of a screening interval and recent reports show that the overall occurrence of these cancers in the screening programme is substantially higher than predicted, especially in the third year after screening.2,3 The occurrence of interval cancers in 79 918 women screened with single-view mammography at three screening units in northwestern England between 1988 and March 31, 1991, is shown in the table. Interval cancers are presented for each year following a negative screen in women above and below the age of 60 at the time of screening. The number of cancers expected to occur in these women, assuming they had not been screened, was estimated by extrapolating from an age-period model,4 allowing for ageing of the cohort and a small general increase in incidence over a calendar year. The relative risk (observed interval cancers/expected number of cancers in the absence of screening) of a breast cancer occurring within 3 years of a negative screen was 0·523 in women aged 50–59 but was 0·317 in the older age group (x2test; p<0·001). Interval cancer targets for the NHS breast screening programme are based on the results of the Swedish Two County Trial, because this large randomised trial achieved a 31% reduction in mortality from breast cancer. In northwestern England interval cancer rates are unacceptably high in younger women but are substantially lower in older women, and only in this latter age group are similar to those achieved in the Swedish Two County Trial.5 If our findings are replicated elsewhere and financial considerations continue to limit the number of tests which the NHS breast Time from negative 1st screen (yr)
<1 1–2 2–3 0–3
Age at first screening (yr) 50–59 (n=53 643)
60–64 (n=26 275)
O
E
O/E
O
E
O/E
34 52 79 165
101·1 105·3 109·0 315·4
0·336 0·494 0·725 0·523
9 13 37 59
59·7 62·1 64·5 186·3
0·151 0·209 0·574 0·317
O=observed number of interval cancers. E=expected numbers of cancers predicted by the age-period model for unscreened women.
Observed (O) and expected (E) number of cancers in relation to age and time from screening
472
4
5
Forrest P. Breast cancer screening: report to the health ministers of England, Scotland and Northern Ireland. London: HM Stationery Office, 1986. Woodman CBJ, Threlfall AG, Boggis CRM, Prior P. Is the three year breast screening interval too long? Occurrence of interval cancers in the NHS breast screening programme’s north western region. BMJ 1995; 310: 224–26. Day N, McCann J, Camilleri-Ferrante C, et al. Monitoring interval cancers in breast screening programmes: the East Anglian experience. J Med Screen 1995; 2: 180–85. Prior P, Wilson S, Woodman CBJ, Threlfall AG. The reliability of underlying incidence rates for estimating the effect and efficiency of screening for breast cancer. J Med Screen 1996; 3: 119–22. Tabar L, Faberberg G, Day NE, Holmberg L. What is the optimum interval between mammographic screening examinations? An analysis based on the latest results of the Swedish two-county breast cancer screening trial. Br J Cancer 1987; 55: 547–51.
Centre for Cancer Epidemiology, Christie Hospital NHS Trust, Withington, Manchester M20 4QL, UK (A G Threlfall)
Infant mortality and the incidence of inflammatory bowel disease Scott M Montgomery, Roy E Pounder, Andrew J Wakefield
The last half of this century has seen a rising incidence of inflammatory bowel disease (IBD) in developed countries. Gent et al suggested that the increasing incidence of Crohn’s disease could be due to delayed exposure to enteric infections.1 We investigated the relation between infant mortality (an indicator of social circumstances and infections in early life) and incidence of IBD. To avoid bias due to changing diagnostic criteria, we used data from the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD), which prospectively identified newly diagnosed cases of IBD with a standard protocol between October, 1991 and September, 1993.2 Published EC-IBD data provided estimates of the incidence of Crohn’s disease and ulcerative colitis in 13 countries in the age range 15–44 years.2 An average was calculated when more than one incidence rate per country was reported. The infant mortality rates in each country for the years 1960–80 were used to calculate an average rate for the period when most of these patients were infants.3–5 The figure shows the relation between infant mortality rate in 1960–80 and the 1991–93 incidence of Crohn’s disease in 15–44 year olds in 13 countries. A lower infant mortality rate is significantly correlated with a higher incidence of Crohn’s disease (Pearson correlation coefficient =–0·71, p=0·006). A similar but weaker relation was found for ulcerative colitis (Pearson correlation coefficient=–0·53, p=0·062; data not shown). The data suggest a threshold effect: once infant mortality drops below a certain level, the incidence of IBD increases at a steeper gradient with decreasing infant mortality. Portugal, which had a relatively high infant mortality, is well below the hypothesised threshold, so its exclusion from the analysis provides information about the relation in countries above the threshold. The Pearson correlation coefficient for the relation of infant mortality with incidence of Crohn’s disease among these 12 countries is –0·84 (p=0·001). These observations may provide a clue to explain the rise in incidence of IBD in recent years, and also the apparent absence of IBD in developing countries where infant mortality is high. A factor associated with lower infant mortality may itself be a risk for developing IBD, such as
Vol 349 • February 15, 1997