- Email: [email protected]
Overdiagnosis of breast cancer in screening
EJSO (2004) 30, 711–712
www.ejso.com
EDITORIAL
Overdiagnosis of breast cancer in screening The recent paper by Zahl et al.1 has again raised doubts about the supposed benefits of breast screening as a public health policy. Theoretically, the introduction of breast screening in risk population should (and does) detect more cancers specifically because of the lead and length time bias, which make the evaluation of a screening programme so difficult. A consequence of these factors is overdiagnosis of breast cancer which is defined as the detection of low malignancy lesions that would otherwise have not been detected in a patients lifetime. The recent reported rates of ‘overdiagnosis’ of breast cancer in Norway (54%) and Sweden (45%) appear to be higher than those expected2 or reported previously3 in clinical trials. However, another recent study of increases in incidence of breast cancer in the screening programme in Italy has also shown an increase in incidence, which varies considerably and reaches 48% in some regions. This increase is primarily in the detection of small (, 10 mm) invasive cancers.4 These findings are consistent with post-mortem studies of patients dying from non-breast cancer causes showing variable rates of asymptomatic invasive and non-invasive breast cancer.5 – 7 Is this reported level of overdiagnosis a problem? One view from the protagonists of breast screening may be that such an increase in the age-specific incidence of breast cancer, especially of small tumours is a testimony to the success of screening.1,8 As these tumours are mostly small, they are potentially curable by surgery and many patients would, therefore, also avoid toxic and/or prolonged adjuvant therapy. It is an incontrovertable fact that survival of patients with small tumours is vastly better than with large tumours for all common solid tumours. Thus, in the UK, the 5-year survival of 95.6% of all screen-detected patients is mostly due to the high proportion of small breast cancers diagnosed within the screening programme.9 In addition, patients detected by screening appear to do better than their symptomatic counterparts.10
The detractors of breast screening point out that many of these tumours would never become symptomatic, and although it has been shown in several studies that breast cancer specific mortality has decreased in countries which have implemented a national screening programme,11 – 13 overall mortality has in general not followed this trend.14 Many would argue that overall mortality should not be the benchmark for the evaluation of a breast screening programme because of the increasingly important effect of other-cause mortality with increasing age.12 However, whilst it is true that the introduction of breast screening programmes in various countries has coincided with better surgery and with the introduction of effective adjuvant treatment for breast cancer, the reductions in mortality from breast cancer are not seen in all countries with no national screening programme.15 What are we therefore to make of the overdiagnosis effect? Zahl et al. have argued that the increased incidence of breast cancer detected by screening should result in a fall in the incidence of breast cancer in older women who are no longer screened. However, their study failed to confirm this in the 70 – 74 year age group and showed only a modest fall of 12% in the . 75 year old age group. This result is probably not surprising. Given that many tumours are small and/or slow growing, one might not expect much of a reduction in the first age cohort not invited for screening as many patients previously attending a screening programme are likely to self refer for further mammography. Furthermore, the reduction in incidence in the . 75 year old cohort was underemphasized. There is no information on the proportion of small tumours in any of the age cohorts and there is no mention of breast cancer specific mortality. There is, therefore, not enough evidence that this degree of overdiagnosis is harmful (at a population level) although clearly patients diagnosed with breast cancer which would have remained occult at an individual level face the prospect of a ‘double
0748-7983/$ - see front matter Q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejso.2004.05.021
712
whammy’—overdiagnosis and, therefore, overtreatment. If overdiagnosis was a problem which related to outcome, one could argue that the recent studies form Sweden, Holland and the UK would not have shown such a large fall in mortality (of 20– 44%) attributable to screening.11 – 13 What can we conclude from all these divergent opinions? Firstly, we share the sentiments expressed by Zahl et al. that breast screening should continue to be rigorously evaluated not just in terms of breast cancer mortality but also in regard to all cause mortality (decreased in the under 50’s). Secondly, we would also agree that patients need to be given more information regarding our uncertainties of benefit of the screening programme as well as the potential risks of the evaluation of a suspicious mammogram.16 We need more research on the outcome of screen detected breast cancer. Are there any benefits from breast cancer screening? There is no doubt that the quality assurance aspects of breast screening programmes have spilled over into the management of patients with symptomatic breast cancer. If the quality of data recording and collection in screening programmes were emulated by the symptomatic service, this would go some way to measure the totality of benefit of the treatment of breast cancer rather than relying on the data from randomised clinical trials. We would then be in a position to know if the benefits of new treatments started to rival the results of treatment in breast screening patients. For now, breast cancer screening should continue with careful evaluation of the programme until we can show that the outcome for symptomatic cancers approaches that of the screened population.
References 1. Zahl PP-H, Strand BH, Maehlen J. Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ 2004;328:921—4. 2. Boer R, Mamerdam P, de Koning H, van Oortmarson G. Extra incidence caused by mammographic screening. Lancet 1994; 343:979. 3. Olsen O, Gotzsche PC. Cochrane review on screening for breast cancer with mammography. Lancet 2001;358: 1340—2. 4. Buiatti E, Barchielli A, Bartolacci M, et al. The impact of
*Corresponding author. Tel./fax: þ44-117-928-4560.
Z. Rayter, E. Kutt
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
organised screening programmes in the stage-specific incidence of breast cancer in some Italian areas. Eur J Cancer 2003;39:1776—82. Anderson J, Nielson M, Christiansen L. New aspects of the natural history of in situ and invasive carcinoma in the female breast: results from autopsy investigations. Verhandlungen der Deutschen Gessellschaft fur Pathologie 1995; 69:88—95. Bartow SA, Pathak DR, Black WC, et al. Prevalence of benign, atypical and malignant breast lesions in populations at different risk of breast cancer: a forensic autopsy study. Cancer 1987;60:2751—60. Nielsen M, Thomsen JL, Primdahl S, et al. Breast cancer and atypia among young and middle aged women: a study of 110 medicolegal autopsies. Br J Cancer 1987;56:814—9. Van den Akker-van Marle ME, Reep-van den Bergh CM, Boer R, Del Moral A, Ascunce N, de Koning HJ. Breast cancer screening in Navarra: interpretation of a high detection rate at the first screening round and low rate at the second screening round. Int J Cancer 1997;73:464—9. NHS Breast Screening Programme and Association of Breast Surgery at BASO. An audit of screen detected breast cancers for the year of screening April 2001 to March 2002. NHS Cancer Screening Programmes 2003. Prasad R, Bryne G, Knox WF, et al. Comparison of survival of screen detected breast cancers (SDBC) with symptomatic ones of same age (50—65 years) in one unit. Eur J Cancer (Suppl) 2003;1:27. Abstract O-88. Tabar L, Yen M-F, Vitak B, et al. Mammography service screening and mortality in breast cancer patients: 20 year follow-up before and after introduction of screening. Lancet 2003;361:1405—10. Blanks RG, Moss SM, McGahan CE, Quinn MJ, Babb PJ. Effect of NHS breast screening programme on mortality from breast cancer in England and Wales 1990—8: comparison of observed with predicted mortality. BMJ 2000;321:665—9. Otto SJ, Fracheboud J, Looman CWN, et al. Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review. Lancet 2003;361:1411—7. Black WC, Haggstrom DA, Welch HG. All-cause mortality in randomised trials of cancer screening. J Natl Cancer Inst 2002;94:167—73. Botha JL, Bray F, Sankila R, Parkin DM. Breast cancer incidence and mortality trends in 16 European countries. Eur J Cancer 2003;39:1718—29. Thornton H. The screening debate: time for a broader approach. Eur J Cancer 2003;39:1807—9.
Z. Rayter* E. Kutt Bristol Breast Unit, Departments of Surgery and Radiology, Bristol Royal Infirmary, Bristol BS2 8HW, UK E-mail address: [email protected] Accepted for publication 25 May 2004
www.ejso.com
EDITORIAL
Overdiagnosis of breast cancer in screening The recent paper by Zahl et al.1 has again raised doubts about the supposed benefits of breast screening as a public health policy. Theoretically, the introduction of breast screening in risk population should (and does) detect more cancers specifically because of the lead and length time bias, which make the evaluation of a screening programme so difficult. A consequence of these factors is overdiagnosis of breast cancer which is defined as the detection of low malignancy lesions that would otherwise have not been detected in a patients lifetime. The recent reported rates of ‘overdiagnosis’ of breast cancer in Norway (54%) and Sweden (45%) appear to be higher than those expected2 or reported previously3 in clinical trials. However, another recent study of increases in incidence of breast cancer in the screening programme in Italy has also shown an increase in incidence, which varies considerably and reaches 48% in some regions. This increase is primarily in the detection of small (, 10 mm) invasive cancers.4 These findings are consistent with post-mortem studies of patients dying from non-breast cancer causes showing variable rates of asymptomatic invasive and non-invasive breast cancer.5 – 7 Is this reported level of overdiagnosis a problem? One view from the protagonists of breast screening may be that such an increase in the age-specific incidence of breast cancer, especially of small tumours is a testimony to the success of screening.1,8 As these tumours are mostly small, they are potentially curable by surgery and many patients would, therefore, also avoid toxic and/or prolonged adjuvant therapy. It is an incontrovertable fact that survival of patients with small tumours is vastly better than with large tumours for all common solid tumours. Thus, in the UK, the 5-year survival of 95.6% of all screen-detected patients is mostly due to the high proportion of small breast cancers diagnosed within the screening programme.9 In addition, patients detected by screening appear to do better than their symptomatic counterparts.10
The detractors of breast screening point out that many of these tumours would never become symptomatic, and although it has been shown in several studies that breast cancer specific mortality has decreased in countries which have implemented a national screening programme,11 – 13 overall mortality has in general not followed this trend.14 Many would argue that overall mortality should not be the benchmark for the evaluation of a breast screening programme because of the increasingly important effect of other-cause mortality with increasing age.12 However, whilst it is true that the introduction of breast screening programmes in various countries has coincided with better surgery and with the introduction of effective adjuvant treatment for breast cancer, the reductions in mortality from breast cancer are not seen in all countries with no national screening programme.15 What are we therefore to make of the overdiagnosis effect? Zahl et al. have argued that the increased incidence of breast cancer detected by screening should result in a fall in the incidence of breast cancer in older women who are no longer screened. However, their study failed to confirm this in the 70 – 74 year age group and showed only a modest fall of 12% in the . 75 year old age group. This result is probably not surprising. Given that many tumours are small and/or slow growing, one might not expect much of a reduction in the first age cohort not invited for screening as many patients previously attending a screening programme are likely to self refer for further mammography. Furthermore, the reduction in incidence in the . 75 year old cohort was underemphasized. There is no information on the proportion of small tumours in any of the age cohorts and there is no mention of breast cancer specific mortality. There is, therefore, not enough evidence that this degree of overdiagnosis is harmful (at a population level) although clearly patients diagnosed with breast cancer which would have remained occult at an individual level face the prospect of a ‘double
0748-7983/$ - see front matter Q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejso.2004.05.021
712
whammy’—overdiagnosis and, therefore, overtreatment. If overdiagnosis was a problem which related to outcome, one could argue that the recent studies form Sweden, Holland and the UK would not have shown such a large fall in mortality (of 20– 44%) attributable to screening.11 – 13 What can we conclude from all these divergent opinions? Firstly, we share the sentiments expressed by Zahl et al. that breast screening should continue to be rigorously evaluated not just in terms of breast cancer mortality but also in regard to all cause mortality (decreased in the under 50’s). Secondly, we would also agree that patients need to be given more information regarding our uncertainties of benefit of the screening programme as well as the potential risks of the evaluation of a suspicious mammogram.16 We need more research on the outcome of screen detected breast cancer. Are there any benefits from breast cancer screening? There is no doubt that the quality assurance aspects of breast screening programmes have spilled over into the management of patients with symptomatic breast cancer. If the quality of data recording and collection in screening programmes were emulated by the symptomatic service, this would go some way to measure the totality of benefit of the treatment of breast cancer rather than relying on the data from randomised clinical trials. We would then be in a position to know if the benefits of new treatments started to rival the results of treatment in breast screening patients. For now, breast cancer screening should continue with careful evaluation of the programme until we can show that the outcome for symptomatic cancers approaches that of the screened population.
References 1. Zahl PP-H, Strand BH, Maehlen J. Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ 2004;328:921—4. 2. Boer R, Mamerdam P, de Koning H, van Oortmarson G. Extra incidence caused by mammographic screening. Lancet 1994; 343:979. 3. Olsen O, Gotzsche PC. Cochrane review on screening for breast cancer with mammography. Lancet 2001;358: 1340—2. 4. Buiatti E, Barchielli A, Bartolacci M, et al. The impact of
*Corresponding author. Tel./fax: þ44-117-928-4560.
Z. Rayter, E. Kutt
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
organised screening programmes in the stage-specific incidence of breast cancer in some Italian areas. Eur J Cancer 2003;39:1776—82. Anderson J, Nielson M, Christiansen L. New aspects of the natural history of in situ and invasive carcinoma in the female breast: results from autopsy investigations. Verhandlungen der Deutschen Gessellschaft fur Pathologie 1995; 69:88—95. Bartow SA, Pathak DR, Black WC, et al. Prevalence of benign, atypical and malignant breast lesions in populations at different risk of breast cancer: a forensic autopsy study. Cancer 1987;60:2751—60. Nielsen M, Thomsen JL, Primdahl S, et al. Breast cancer and atypia among young and middle aged women: a study of 110 medicolegal autopsies. Br J Cancer 1987;56:814—9. Van den Akker-van Marle ME, Reep-van den Bergh CM, Boer R, Del Moral A, Ascunce N, de Koning HJ. Breast cancer screening in Navarra: interpretation of a high detection rate at the first screening round and low rate at the second screening round. Int J Cancer 1997;73:464—9. NHS Breast Screening Programme and Association of Breast Surgery at BASO. An audit of screen detected breast cancers for the year of screening April 2001 to March 2002. NHS Cancer Screening Programmes 2003. Prasad R, Bryne G, Knox WF, et al. Comparison of survival of screen detected breast cancers (SDBC) with symptomatic ones of same age (50—65 years) in one unit. Eur J Cancer (Suppl) 2003;1:27. Abstract O-88. Tabar L, Yen M-F, Vitak B, et al. Mammography service screening and mortality in breast cancer patients: 20 year follow-up before and after introduction of screening. Lancet 2003;361:1405—10. Blanks RG, Moss SM, McGahan CE, Quinn MJ, Babb PJ. Effect of NHS breast screening programme on mortality from breast cancer in England and Wales 1990—8: comparison of observed with predicted mortality. BMJ 2000;321:665—9. Otto SJ, Fracheboud J, Looman CWN, et al. Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review. Lancet 2003;361:1411—7. Black WC, Haggstrom DA, Welch HG. All-cause mortality in randomised trials of cancer screening. J Natl Cancer Inst 2002;94:167—73. Botha JL, Bray F, Sankila R, Parkin DM. Breast cancer incidence and mortality trends in 16 European countries. Eur J Cancer 2003;39:1718—29. Thornton H. The screening debate: time for a broader approach. Eur J Cancer 2003;39:1807—9.
Z. Rayter* E. Kutt Bristol Breast Unit, Departments of Surgery and Radiology, Bristol Royal Infirmary, Bristol BS2 8HW, UK E-mail address: [email protected] Accepted for publication 25 May 2004