screening women aged 40–49 years

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Screening women aged 4049 years Sue Moss Cancer Screening Evaluation Unit, Institute of Cancer Research, Sir Richard Doll Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK abstract article info Available online 24 June 2011 Keywords: Mammography Screening Age Recent recommendations have reignited the debate about mammographic screening in women below age 50 years. Evidence from randomised controlled trials and results from service screening in some countries show a benet of screening women below age 50 with a screening interval of up to two years. The benet of such screening in terms of mortality reduction will be lower than that in older women, whilst potential harms include false positive screens and resulting anxiety, risk of overdiagnosis and possible radiation risk. .The balance of benets to possible harms, and the perception of this balance will vary both according to individual priorities and risk. Minimising harms and identifying those women who will benet most from screening should remain a priority. © 2011 Elsevier Inc. All rights reserved. The US Preventive Services Task Force (USPSTF) has recently revived the long-running controversy about the question of mam- mographic screening for women between the ages of 40 and 49 (U.S. Preventive Services Task Force, 2009). Their recommendation against routine screening at these ages states that the decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient's values regarding specic benets and harms. The basis for these recommendations was an updated systematic review (Nelson et al., 2009), together with a decision analysis using population modelling to predict the outcomes of different screening scenarios (Mandelblatt et al., 2009). The publication of these recommendations generated extensive and sometimes heated correspondence, largely concerned with the relative harms and benets of screening in younger women, and the most appropriate ways of balancing the two, but also debating the extent to which the recommendations had been driven by nancial considerations (Begg, 2010). This latest controversy follows a long running debate on the issue of screening in young women. In 1997 a US National Institutes of Health (NIH) consensus conference concluded that the data then available did not warrant a universal recommendation for mammog- raphy for all women in their forties, a decision that was subsequently reversed (Calvocoressi et al., 2008; NIH Consensus Statement, 1997). The current European Council recommendation is for screening women aged 50 to 69 years (Council of the European Union, 2003). Effectiveness of screening For women aged 3949 the systematic review conducted for the USPSTF included 8 trials, with a time span ranging from the US Health Insurance Plan trial in the 1960's (Habbema et al., 1986) to the UK Age trial conducted in the 1990's (Moss et al., 2006). The combined results of these trials indicated a 15% reduction in breast cancer mortality in favour of screening, (RR 0.85, 95% CI 0.750.96), calculated on an intention to treat basis(i.e. comparing women invited to screening with those not invited). This corresponded to a number needed to be invited for screening to prevent one breast cancer death of 1904 (95% CI 929, 6374) over 2 to 9 screening rounds, depending on the trial, and with 11 to 20 years of follow-up. Whilst the trials were conducted over an extended time period, the most recent UK trial, and one of only two designed specically to address the question of screening below age 50, produced a result that, although non-signicant, was nevertheless consistent with those from earlier trials. The UK Age trial is unique in studying the effect of starting annual screening at age 40 years. In settings where screening below age 50 has been undertaken on a population basis, there is evidence of effectiveness in terms of mortality reduction. In Sweden, a recent study comparing breast cancer mortality between areas that did and did not invite women aged 40 to 49 years to attend mammography screening found a reduction of 26% (RR 0.74, 95% CI 0.660.83) in women invited, and of 29% (RR 0.71, 95% 0.620.80) in those attending (Hellquist et al., 2011). The screening interval varied between 18 and 24 months. A casecontrol study from the Netherlands of biennial mammog- raphy in Nijmegen, the Netherlands found an odds ratio of 0.50 (95% CI 0.300.82) of breast cancer mortality in screened vs unscreened women, a result similar to that in women aged 5059 years (van Schoor et al., 2010). In general there is consensus that screening in young women has a benet in terms of mortality reduction, though less than that in older women. However, contentious issues remain about the magnitude of the harms of screening, and the extent to which the benet is observed in the impact of population based screening. Preventive Medicine 53 (2011) 105107 E-mail address: [email protected]. 0091-7435/$ see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.ypmed.2011.06.006 Contents lists available at ScienceDirect Preventive Medicine journal homepage: www.elsevier.com/locate/ypmed

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Page 1: Screening women aged 40–49 years

Preventive Medicine 53 (2011) 105–107

Contents lists available at ScienceDirect

Preventive Medicine

j ourna l homepage: www.e lsev ie r.com/ locate /ypmed

Screening women aged 40–49 years

Sue MossCancer Screening Evaluation Unit, Institute of Cancer Research, Sir Richard Doll Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK

E-mail address: [email protected].

0091-7435/$ – see front matter © 2011 Elsevier Inc. Aldoi:10.1016/j.ypmed.2011.06.006

a b s t r a c t

a r t i c l e i n f o

Available online 24 June 2011

Keywords:MammographyScreeningAge

Recent recommendations have reignited the debate about mammographic screening in women below age50 years. Evidence from randomised controlled trials and results from service screening in some countriesshow a benefit of screening women below age 50 with a screening interval of up to two years. The benefit ofsuch screening in terms of mortality reduction will be lower than that in older women, whilst potential harmsinclude false positive screens and resulting anxiety, risk of overdiagnosis and possible radiation risk. .Thebalance of benefits to possible harms, and the perception of this balance will vary both according to individualpriorities and risk. Minimising harms and identifying those women who will benefit most from screeningshould remain a priority.

l rights reserved.

© 2011 Elsevier Inc. All rights reserved.

The US Preventive Services Task Force (USPSTF) has recentlyrevived the long-running controversy about the question of mam-mographic screening for women between the ages of 40 and 49 (U.S.Preventive Services Task Force, 2009). Their recommendation againstroutine screening at these ages states that ‘the decision to startregular, biennial screening mammography before the age of 50 yearsshould be an individual one and take patient context into account,including the patient's values regarding specific benefits and harms’.

The basis for these recommendations was an updated systematicreview (Nelson et al., 2009), together with a decision analysis usingpopulation modelling to predict the outcomes of different screeningscenarios (Mandelblatt et al., 2009).

The publication of these recommendations generated extensiveand sometimes heated correspondence, largely concerned with therelative harms and benefits of screening in younger women, and themost appropriate ways of balancing the two, but also debating theextent to which the recommendations had been driven by financialconsiderations (Begg, 2010).

This latest controversy follows a long running debate on the issueof screening in young women. In 1997 a US National Institutes ofHealth (NIH) consensus conference concluded that the data thenavailable did not warrant a universal recommendation for mammog-raphy for all women in their forties, a decision that was subsequentlyreversed (Calvocoressi et al., 2008; NIH Consensus Statement, 1997).The current European Council recommendation is for screeningwomen aged 50 to 69 years (Council of the European Union, 2003).

Effectiveness of screening

For women aged 39–49 the systematic review conducted for theUSPSTF included 8 trials, with a time span ranging from the US Health

Insurance Plan trial in the 1960's (Habbema et al., 1986) to the UK Agetrial conducted in the 1990's (Moss et al., 2006). The combined resultsof these trials indicated a 15% reduction in breast cancer mortality infavour of screening, (RR 0.85, 95% CI 0.75–0.96), calculated on an‘intention to treat basis’ (i.e. comparing women invited to screeningwith those not invited). This corresponded to a number needed to beinvited for screening to prevent one breast cancer death of 1904 (95%CI 929, 6374) over 2 to 9 screening rounds, depending on the trial, andwith 11 to 20 years of follow-up.

Whilst the trials were conducted over an extended time period,the most recent UK trial, and one of only two designed specifically toaddress the question of screening below age 50, produced a resultthat, although non-significant, was nevertheless consistent with thosefrom earlier trials. The UK Age trial is unique in studying the effect ofstarting annual screening at age 40 years.

In settings where screening below age 50 has been undertaken ona population basis, there is evidence of effectiveness in terms ofmortality reduction. In Sweden, a recent study comparing breastcancer mortality between areas that did and did not invite womenaged 40 to 49 years to attend mammography screening found areduction of 26% (RR 0.74, 95% CI 0.66–0.83) in women invited, and of29% (RR 0.71, 95% 0.62–0.80) in those attending (Hellquist et al.,2011). The screening interval varied between 18 and 24 months.

A case–control study from the Netherlands of biennial mammog-raphy in Nijmegen, the Netherlands found an odds ratio of 0.50 (95%CI 0.30–0.82) of breast cancer mortality in screened vs unscreenedwomen, a result similar to that in women aged 50–59 years (vanSchoor et al., 2010).

In general there is consensus that screening in young women has abenefit in terms of mortality reduction, though less than that in olderwomen. However, contentious issues remain about the magnitude ofthe harms of screening, and the extent to which the benefit isobserved in the impact of population based screening.

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106 S. Moss / Preventive Medicine 53 (2011) 105–107

Harms of screening

A widely quoted study in the US found a cumulative risk of falsepositive mammography results in women aged 40–49 of 56% after 10screens (Elmore et al., 1998). More recently, the UK Age trial hasfound a cumulative risk over 7 annual screens of 20.5% (Johns et al.,2010), the false positive rates being similar to those in older women,but with a lower positive predictive value of referral for cancer due tothe lower cancer detection rate. Minimising the recall rate whistmaintaining a sufficiently high cancer detection rate is an importantgoal.

Psychological distress is increasingly cited as an adverse effect ofmammographic screening. Such distress is most likely to occur inwomen recalled for further assessment, and thus it may have agreater proportionate effect (relative to benefits) in younger women(Brewer et al., 2007). A systematic review of psychological distressassociated with the diagnostic phase of suspected breast cancers,whilst not specifically studying screening related distress, found noassociation between younger age and increased psychologicaldistress (Montgomery, 2010). In the UK Age trial, women withprevious false positivemammogramswere no less likely to attend forsubsequent screening (Johns et al., 2010), although no information isavailable on the reasons for re-attendance i.e. whether due tocontinuing anxiety, or to reassurance from previous screening.

The extent of overdiagnosis, both of invasive disease and inparticular of ductal carcinoma in situ, remains one of the greatestareas of debate in mammography screening, but is difficult to quantifyoutside randomised controlled trials. In women aged 50 years andover, estimates of the extent of overdiagnosis vary widely from 1% to30% (Nelson et al., 2009). At younger ages, overdiagnosis due to thediagnosis of cases by screening where death would otherwise haveoccurred before the time of clinical presentation will be less com-mon due to longer life expectancy; however conversely where over-diagnosis does occur it may have a greater impact in terms of qualityof life.

The risk of radiation induced breast cancer from screening remainsa concern in younger women due to increased risk with younger ageat exposure (Preston et al., 2002). However for a mortality reductionof at least 20% in women screened (Berrington de Gonzalez et al.,2005) the benefit has been estimated to outweigh the risk, and arecent study using a different exposure-risk model found a lowerestimated radiation risk (de Gelder et al., 2011).

Balancing benefits and harms

The balance of harms and benefits is difficult to quantify, and islikely to be viewed differently according to individual perception.However it is also necessary to use the same basis for harms andbenefit as far as possible, and in particular to avoid confusion betweenthe benefits calculated for women invited (the ‘intention to treatapproach’), and harms which are often based on the effects in anindividual woman actually screened (Dean, 2010). Quantifying thebenefit to an individual woman in terms of the average life yearssaved per woman screened or invited (Hoerger et al., 2011) is nothelpful to the making of an informed choice about screening.

The number needed to screen (NNS) is a useful means of relatingthe benefits of screening to the harms; it implicitly addresses thedisadvantages associated with regular screening which will includefalse positive results and the associated anxiety, risk and overdiag-nosis, and risk due to radiation, as well as the financial cost. However,the NNS is dependent on the duration and length of follow upavailable, hampering comparison across studies. In the UK Age trial,the NNS (actually number needed to be invited) was estimated as2512 women invited for 7–9 years to prevent one death over 10 yearsof follow up, and the number needed to be screened was 1777 (Mosset al., 2006). The higher numbers than those estimated in the meta-

analysis may be due to shorter average follow up. As seen, it is alsodifficult to avoid the issue of financial cost in forming recommenda-tions, in part due to the emphasis placed on the number needed toscreen (NNS).

The results of the decision analysis by Mandelbatt et al., suggestedthat biannual screening might produce almost as great a benefit asannual screening with fewer potential harms. However the assump-tions made about the variation of natural history with age are notexplicit. In the UK Age trial, in which women were invited annually,the sensitivity of mammographywas estimated as 73.6% following thefirst (two-view) screen based on proportional incidence in the first12 months (Moss et al., 2005), although it was lower followingsubsequent single view screens. Improved sensitivity, for examplefrom digital mammography, may have implications for the screeninginterval.

Conclusion

The lower incidence of breast cancer at younger ages means thatinevitably the absolute benefit in terms of mortality reduction will beless. The Swedish study found a lesser effect in women aged 40–44that those aged 45–49. Nevertheless the fact that deaths will beprevented at younger ages means that consideration of life-yearssaved reduces this disparity. For women at increased risk of breastcancer due to family history, the absolute benefit will be greater, andmore likely to outweigh possible harms.

Whilst possible reasons for a lesser benefit ofmammography inyoungwomen include greater mammographic density and possibly fastergrowth rate of tumours, several authors have pointed out that thesefactorswill change continuouslywith age (Kopans, 2010),meaning that adichotomous change in policy at age 50maynot be themost appropriate.

There will inevitably be financial considerations, depending on thehealth care setting, involved in decisions on the age fromwhichwomenshould be offered or be eligible for screening. Reducing harms can beachieved, for example, by minimising recall rates as far as possible;longer screening intervals will also reduce overall harms and may beincreasingly effective with new and more sensitive technologies.Meanwhile there will be a continuum of benefit and risk ratio, andsubgroups of women for whom the balance differs. For women at allages, identifying thosewhowill benefitmost (and least) from screeningshould remain a priority for further research.

Conflict of interest statement

None declared.

References

Begg, C.B., 2010. The background review for the USPSTF recommendation on screeningfor breast cancer. Annals of Internal Medicine 152 (8), 540–541.

Berrington de Gonzalez et al, 2005. Mammographic screening before age 50 years in theUK: comparison of the radiation risks with the mortality benefits. British Journal ofCancer 93 (5), 590–596.

Brewer, N.T., Salz, T., Lillie, S.E., 2007. Systematic review: the long-term effects of false-positive mammograms. Annals of Internal Medicine 146 (7), 502–510.

Calvocoressi, L., Sun, A., Kasl, S.V., Claus, E.B., Jones, B.A., 2008. Mammography screeningof women in their 40s— impact of changes in screening guidelines. Cancer 112 (3),473–480.

Council of the European Union, 2003. Council recommendation. Official Journal of theEuropean Unionhttp://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2003:327:0034:0038:EN:PDF.

de Gelder, R., Draisma, G., Heijnsdijk, E.A., de Koning, H.J., 2011. Population-basedmammography screening below age 50: balancing radiation-induced vs preventedbreast cancer deaths. British Journal of Cancer 104 (7), 1214–1220.

Dean, P.B., 2010. Comments and response on the USPSTF recommendation on screeningfor breast cancer. Annals of Internal Medicine 152 (8), 539.

Elmore, J.G., Barton, M.B., Moceri, V.M., Polk, S., Arena, P.J., Fletcher, S.W., 1998. Ten-yearrisk of false positive screening mammograms and clinical breast examinations. TheNew England Journal of Medicine 338 (16), 1089–1096.

Habbema, J.D., van Oortmarssen, G.J., Van Putten, D.J., Lubbe, J.T., van der Maas, P.J.,1986. Age-specific reduction in breast cancer mortality by screening: an analysis of

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Hellquist, B.N., Duffy, S.W., Abdsaleh, S., et al., 2011. Effectiveness of population-based servicescreeningwithmammography forwomenages40 to49 years: evaluationof theSwedishMammography Screening in Young Women (SCRY) cohort. Cancer 117 (4), 714–722.

Hoerger, T.J., Ekwueme, D.U., Miller, J.W., et al., 2011. Estimated effects of the nationalbreast and cervical cancer early detection program on breast cancer mortality.American Journal of Preventive Medicine 40 (4), 397–404.

Johns, et al., 2010. False-positive results in the randomized controlled trial ofmammographic screening from age 40 (“Age” trial). Cancer Epidemiology,Biomarkers & Prevention 19 (11), 2758–2764.

Kopans, D.B., 2010. The recent US preventive services task force guidelines are notsupported by the scientific evidence and should be rescinded. Journal of theAmerican College of Radiology 7 (4), 260–264.

Mandelblatt, J.S., Cronin, K.A., Bailey, S., et al., 2009. Effects of mammography screeningunder different screening schedules: model estimates of potential benefits andharms. Annals of Internal Medicine 151 (10), 738–747.

Montgomery, M.e.a, 2010. Psychological distress associated with the diagnostic phase forsuspected breast cancer: systematic review. Journal of Advanced Nursing 66 (11),2372–2390.

Moss, S., Thomas, I., Evans, A., Thomas, B., Johns, L., 2005. Randomised controlled trial ofmammographic screening in women from age 40: results of screening in the first10 years. British Journal of Cancer 92 (5), 949–954.

Moss, S.M., Cuckle, H., Evans, A., Johns, L., Waller, M., Bobrow, L., 2006. Effect ofmammographic screening from age 40 years on breast cancer mortality at10 years' follow-up: a randomised controlled trial. The Lancet 368 (9552),2053–2060.

Nelson, H.D., Tyne, K., Naik, A., Bougatsos, C., Chan, B.K., Humphrey, L., 2009. Screeningfor breast cancer: an update for the U.S. Preventive Services Task Force. Annals ofInternal Medicine 151 (10), 727–742.

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Preston, D.L., Mattsson, A., Holmberg, E., Shore, R., Hildreth, N.G., Boice Jr., J.D., 2002.Radiation effects on breast cancer risk: a pooled analysis of eight cohorts. RadiationResearch 158 (2), 220–235.

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van Schoor, G., Moss, S.M., Otten, J.D., et al., 2010. Effective biennial mammographicscreening in women aged 40–49. European Journal of Cancer 46 (18), 3137–3140.