Breast cancer mortality after screening mammography in British Columbia women

Andrew Coldman1*, Norm Phillips

1, Linda Warren

2and Lisa Kan

2

1Surveillance and Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Canada2Screening Mammography Program of BC, British Columbia Cancer Agency, Vancouver, BC, Canada

Mammographic screening is a proven method for the early detec-tion of breast cancer. The authors analyzed the impact of servicemammographic screening on breast cancer mortality amongBritish Columbia women who volunteered to be screened by theScreening Mammography Program of British Columbia. A cohortof women having at least one mammographic screen by ScreeningMammography Program of British Columbia between the ages of40 and 79 in the period 1988–2003 was identified. All cases anddeaths from breast cancer occurring in British Columbia wereidentified from the British Columbia Cancer Registry and linkedto the screening cohort. Expected deaths from breast cancer in thecohort were calculated using incidence and survival rates forBritish Columbia women not in the cohort. Adjustment was madefor age and socioeconomic status of their area of residence at timeof diagnosis. The breast cancer mortality ratio was calculated bydividing observed by expected breast cancer deaths. The mortalityratio (95% confidence interval) was 0.60 (0.55, 0.65) for all agescombined (p < 0.0001). The mortality ratio in women aged 40–49at first screening was 0.61 (0.52, 0.71), similar to that in womenover 50 (p 5 0.90). Exclusion of mortality associated with breastcancers diagnosed after age 50 in women starting screening intheir 40s increased the mortality ratio to 0.63 (0.52, 0.77), but itremained statistically significant. Correction for self-selection biasusing estimates from the literature increased the mortality ratiofor all ages to 0.76. Mammographic screening at all ages between40 and 79 reduced subsequent mortality rates from breast cancer.' 2006 Wiley-Liss, Inc.

Key words: screening; breast cancer; mammography

Meta-analyses of clinical trials have shown reductions in breastcancer and overall mortality in women randomized to receivescreening mammography.1 Consequently, screening mammographyhas become a recommended method for the early detection of breastcancer in many countries.2 However, uncertainties still exist regard-ing the value of screening at different ages3 and at different frequen-cies.1,4 Trials conducted in Canada failed to find an effect of screen-ing including mammography in women aged 40–495 or comparingmammography with physical examination in women 50–59.6 Fur-ther trials are currently underway7,8 to try to provide further evi-dence. The existence of service screening in different countries overthe last 2 decades has provided added information on the impact ofscreening mammography.9–12 The overall contribution of mammo-graphic screening to declines in population breast cancer mortalityrates is an area of some uncertainty, with some authors estimatingeffects as large as 65%13 and others arguing for little or no effect.14

The Screening Mammography Program of British Columbia(SMPBC) was established in 1988 to provide breast screening towomen in British Columbia.15 Women aged 40–79 were eligibleto self-refer and received screening mammograms free of chargethrough community clinics with interpretation by radiologistsaffiliated to the program.16 Currently, women under the age of 50are rescreened annually and those over 50 every 2 years. As theprogram grew, participation rates have increased so that by 2003over 50% of British Columbia women aged over 40 had receivedat least one screening mammogram through the program.

To provide additional information on the potential of mammog-raphy screening to reduce deaths from breast cancer, we undertookan analysis of mortality from breast cancer in women who partici-pated in the SMPBC and compared their observed outcomes withwhat would be expected based upon incidence and survival ratesfor other British Columbia women who have not participated.

Material and methods

Data were obtained from the SMPBC database of women re-ceiving screening mammography through the program, the BritishColumbia Cancer Registry (BCCR) and the Vital StatisticsAgency death file (VSA) comprising death notifications in BritishColumbia residents.

The study cohort consisted of women aged 40 or more firstscreened by SMPBC between January 1988 and December 2003.Women entered the cohort at the date of their first SMPBC mammo-gram. Breast cancer cases and deaths in the cohort were ascertainedthrough linkage with the VSA and BCCR. Linkage was performedin 2 steps. First the VSA and BCCR were linked to identify thecause and dates of death in all breast cancer cases diagnosed in thestudy period. A second linkage was performed of the study cohortto the VSA and BCCA to identify dates of death and cases of breastcancer in the study cohort. Combination of the resulting files permit-ted the identification of breast cancer cases and deaths for BritishColumbia women, in the cohort and not in the cohort, throughoutthe study period. Linkage was performed using Automatch,17 withpersonal health number (a unique identifier of the publicly fundedmedical plan), address, name (first, middle, last and birth) and datesof birth and diagnosis as linking variables as appropriate. This link-age also identified deaths from all causes in the cohort.

The resulting data for the cohort consisted of dates of birth, death,entry to the cohort, and first breast cancer, postal code of residenceat last screen, details of breast cancer and cause of death. The dataon breast cancer cases not in the cohort consisted of dates of birth,death and first breast cancer, details of breast cancer and cause ofdeath. The number of expected deaths from breast cancer in thecohort was calculated using the method described by Sasieni,18

which utilizes the age-specific time-at-risk of the cohort and re-quires the specification of age-specific incidence and survival ratesexpected without screening.

Age-specific incidence rates of breast cancer were calculatedusing data from the SMPBC, BCCR and published population countsfor British Columbia. Rates were calculated in the usual way, withthose in nonparticipants of SMPBC being calculated by subtractingSMPBC cancers and populations counts from the respective age-spe-cific totals for the whole population by study year (1988–2003).In situ cancers were not included in the calculation of incidencerates. Statistical comparison of cancer incidence rates was madeusing a general linear model19 with a Poisson error distribution.

Breast cancer specific survival rates were estimated and ana-lyzed using Cox regression20 on cancers diagnosed in the popula-tion between 1985 and 2003 with data taken from the BCCR andVSA. Both age, in decade categories, period of diagnosis and av-erage personal income of area of residence in intervals defined byquartiles were included in the Cox analysis. Median familyincome was obtained from tax return information for 1996 and is

Grant sponsor: American Cancer Society; Grant number: 23039.*Correspondence to: British Columbia Cancer Agency, Suite 800, 686

W Broadway, Vancouver, BC V5Z 1G1, Canada. Fax: 1-604-660-3645.E-mail: acoldman@bccancer.bc.caReceived 23 January 2006; Accepted after revision 3 July 2006DOI 10.1002/ijc.22249Published online 5 December 2006 in Wiley InterScience (www.interscience.

wiley.com).

Int. J. Cancer: 120, 1076–1080 (2006)' 2006 Wiley-Liss, Inc.

Publication of the International Union Against Cancer

aggregated for a unit based on the postal code which contains amaximum of 440 households per unit.21

Cases of in situ cancer and those registered by death certificatealone were excluded from the calculation of incidence and sur-vival in nonparticipants. All deaths attributed to breast canceroccurring within the study cohort were included in the calculationof observed deaths if they occurred within the study period.

The SMPBC has a high retention rate, with 80% (90%) ofwomen returning within 30 (60) months for another mammog-raphy screen.22 However, subjects leaving the province may nothave their residence status updated. To estimate the effect ofundocumented emigration on the time-at-risk of the cohort, a ran-dom sample of 200 women was drawn from the SMPBC databaseamong those not having returned in 4 years after their last screen.Their last known address and their general practitioners officewere contacted by telephone to ascertain their current residency.The result was then used to adjust the years-at-risk.

Observed and expected breast cancer mortality rates were cal-culated with cohort members considered to be at risk from entryuntil the first of death or December 2003. The calculation ofexpected used incidence and survival rates derived from nonparti-cipants. Calculation was also performed excluding deaths, bothobserved and expected, associated with nonscreen detected can-cers diagnosed within 6 months of date of first screening. The pur-pose of this exclusion was to remove any effect of preexistingsymptomatic cases, which are present in population rates butunlikely to be present in screening populations at entry. Forwomen first screened before age 50, calculations were repeatedexcluding deaths, both observed and expected, associated withcancers diagnosed after age 50.

Observed and expected breast cancer mortality was comparedassuming observed deaths to be Poisson distributed with meanvalue given by the expected mortality. The mortality ratio was cal-culated as the ratio of observed to expected mortality and confi-dence intervals were based upon Poisson statistics with allowancefor sampling variation of the expected.

Results

There were 598,690 women in the cohort who underwent a totalof 2,196,441 mammograms in the period 1988–2003 for an aver-age of 3.7 screens per woman. Record linkage identified 14,247

breast cancers in the cohort in the study period (Table I). Therewere a further 19,913 invasive breast cancers reported to theBCCR in British Columbia women not in the cohort during thestudy period.

In the random sample of 200 women who had not returned forscreening in 4 or more years, current residence could not be ascer-tained in 17 and among the known 15% (27/183) were no longerBC residents. Assuming the probability of migration to be uniformin time, the above information along with the observed pattern ofreturn for screening indicated that the average annual out-migrationrate for the cohort yielded 8.1 per 1,000 women per year. This ratewas used to correct the person-years of follow-up in the cohort.

The age-specific incidence rates of breast cancer for women notin the study cohort in 1988–2003 Non-SMP and in the British Co-lumbia population in 1985–1987 Pre-SMP are given in Figure 1.The age-specific population rates for 1985–1987 and for the non-participants were similar and the latter was used in the calculationof expected mortality of the cohort.

The survival rates of breast cancer in women aged 40–79 at diag-nosis not in the study cohort in 1988–2003 Non-SMP and in theBritish Columbia population in 1985–1987 Pre-SMP are given inFigure 2. Survival rates were higher in those women not in thecohort 1988–2003 than in all British Columbia breast cancer casesdiagnosed in the period 1985–1987 and thus the 1988–2003 caseswere used for the calculation of expected mortality. To control forpotential survival confounders, a Cox model was fit to the 1988–2003 nonmembers of the cohort with factors for age at diagnosis(40–49, 50–59, 60–69 and 701), calendar period of diagnosis (pre-versus post-1996) and median income level of area of residence(<40, 40–50, 50–60, 60–70, 701 thousand dollars). Age and areasignificantly effected survival and the categories were collapsedinto homogeneous categories (Table II). The results from the result-ing survival model were then applied, with the incidence rate, tocalculate expected mortality for cohort members based on their ageand region of residence while at risk in the cohort using the methoddescribed by Sasieni.18

The observed and expected number of deaths and mortality ra-tio by age-decade of starting screening are given in Table III. The

TABLE I – NUMBER OF WOMEN BY AGE AND YEAR, AND NUMBER OFCANCER CASES BY AGE, YEAR AND MODE OF DETECTION IN THECOHORT OF WOMEN SCREENED AT LEAST ONCE THROUGH THESCREENING MAMMOGRAPHY PROGRAM OF BRITISH COLUMBIA

BETWEEN 1988 AND 2003

Factor Category

Numberof womenenteringcohort

Breast cancerdiagnoses

Invasive In situ

Age (years) 40–49 275,577 1,912 55750–59 157,403 3,387 80460–69 105,298 3,248 66170–79 53,588 2,639 446801 6,825 546 47

Calendar period 1988–1991 69,872 381 861992–1995 172,939 1,988 3741996–1999 215,144 4,029 8752000–2003 140,766 5,334 1,180

Mode ofdetectionof cancers

Screen detected 7,081 1,973Post screen�12 months

1,504 192

Post screen13–24 months

1,482 164

Post screen25–36 months

578 76

Post screen371 months

1,087 110

FIGURE 1 – Age-specific incidence rates of breast cancer in non-participants (Non-SMP) of the Screening Mammography Program ofBritish Columbia in the period 1988–2003 and the British Columbiafemale population 1985–1987 (Pre-SMP).

1077BREAST CANCER MORTALITY AFTER SCREENING

mortality ratio was similar for each of the age ranges (p 5 0.90).Observed and expected mortality rates were low in the initial yearsafter entry into the cohort and the ratio of observed to expectedbreast cancer deaths stabilized beyond 5 years. Exclusion ofdeaths associated with cancers occurring within 6 months of first

screening increased the mortality ratio for all age groups by 0.03–0.05 for all age groups (Table III). The observed and expected cu-mulative mortality rates by time since entry into the cohort (firstscreen) for women aged 40–49 at first screen is shown in Figure 3.Figure 3 illustrates that observed and expected breast cancer mor-tality increases slowly in the first 4 years after cohort entry reflect-ing the absence of symptomatic disease at first screening, but sub-sequently increases more rapidly. Expected mortality rates exceedobserved from 2 years after first screening.

The observed number of cancers occurring in the cohort prior toage 50, 2,469, exceeded the expected, 1,492, reflecting the effectof earlier detection. In contrast, observed numbers (Table III), andrates (Fig. 3), of breast cancer deaths for cases diagnosed prior toage 50 were less than expected. Restriction to cases diagnosedbefore age 50 caused the mortality ratio to increase from 0.61 to0.65 but it remained significant (p < 0.0001), indicating that theobserved mortality reduction was not due to screening after theage of 50 in this group. Figure 3 also shows that observed mortal-ity rates are less than the expected rates after limiting deaths towomen in whom diagnosis occurred prior to age 50.

Discussion

It is generally accepted that mammographic screening reducesbreast cancer mortality in women over the age of 50 and it is rec-ommended in most western countries. Mammography screening inwomen under the age of 50 has been more controversial regardingits efficacy and effectiveness. Recent meta-analyses of random-ized screening trials of women under the age of 50 provide evi-dence of a significant 18% mortality reduction23 a little smallerthan that found after age 50.1,24 A population study in Swedenfound a greater magnitude of reductions in both age groups.10

Analysis using a simulation model, based on data from screeningtrials conducted in Sweden, suggested that as much as 70% of theobserved reduction in women aged 40–49 at start of screening

TABLE III – OBSERVED AND EXPECTED DEATHS FROM BREAST CANCER, MORTALITY RATIO WITHCONFIDENCE INTERVALS (CI) AND P-VALUE FOR DIFFERENCES IN RATIOS BY AGE AT FIRST SCREENING

AND ASSUMED TIME AT RISK FOR CANCER DIAGNOSIS

Assumed time at risk forcancer diagnosis

Age at firstscreening (years)

Number of deathsMortality ratio (95% CI)1

1

pObserved Expected

From first screen 40–49 202 333 0.61 (0.52,0.71) 0.9050–59 194 331 0.59 (0.50,0.69)60–69 213 353 0.60 (0.52,0.70)701 147 235 0.63 (0.52,0.75)

From 6 months afterfirst screen2

40–49 195 307 0.64 (0.54,0.74) 0.8750–59 189 300 0.63 (0.53,0.75)60–69 209 324 0.65 (0.55,0.76)701 143 211 0.68 (0.57,0.81)

From 6 months after firstscreen until age 502

40–49 121 191 0.63 (0.52,0.77) 0.483

1Mortality ratio 5 observed deaths/expected deaths.–2Observed deaths include those arising from can-cers detected at first screen but not interval cancers in first 6 months.–3Compared with the rate for allaged 40–49 in first row of table.

TABLE II – SURVIVAL ESTIMATES, HAZARD RATIOS AND CONFIDENCE INTERVALS OBTAINED FROMPROPORTIONAL HAZARDS ANALYSIS OF INVASIVE CANCERS DIAGNOSED BETWEEN 1988 AND 2003

IN WOMEN NOT PARTICIPATING IN THE SCREENING MAMMOGRAPHY PROGRAM OF BRITISH COLUMBIA

Variable Category Numberof cases

Hazardratio

95% confidenceinterval forhazard ratio

Age 40–49 4,083 0.91 (0.83,0.99)50–69 7,963 1 –701 7,743 1.27 (1.19,1.36)

Median familyincome

<$70,000 18,868 1 –$70,0001 921 0.78 (0.67,0.91)

Baseline diseasespecific survivalestimates

3 years 5 years 10 years0.887 0.835 0.749

FIGURE 2 – Breast cancer-specific survival curves in women aged40+ at diagnosis who were non-participants (Non-SMP) of the Screen-ing Mammography Program of British Columbia in the period 1988–2003 or resident in British Columbia 1985–1987 (Pre-SMP).

1078 COLDMAN ET AL.

may be due to screening performed after the age of 50.25 A subse-quent analysis based on the same trials came to a somewhat differ-ent conclusion, finding almost all of the observed mortality reduc-tion resulted from screening before the age of 50.26 The results ofthe study presented are supportive of the conclusion that mammo-graphic screening does reduce mortality from breast cancer andthat the proportionate mortality reduction is similar at ages above40, although the magnitude of effect may be dependent upon thescreening frequency. In current British Columbia practice, theshorter sojourn time (the time spent in an asymptomatic mammo-graphically detectable state) in younger women is compensatedfor by screening more frequently,4,27 with women being recom-mended to return annually before age 50 and biennially thereafter.

The analysis of recent service data from population-based screen-ing programs can provide information upon the impacts of screeningin settings where adjuvant systemic therapy is commonplace. Byrestricting attention to women entering screening it is easier to iden-tify the effects of screening when population uptake has graduallyincreased over a long period, such as in British Columbia. As such,this study measures efficacy and not effectiveness. The cohort na-ture of this study design also permits the effects of screening to beevident earlier than using population mortality statistics since theseinclude deaths from nonparticipants and cases diagnosed prior tothe introduction of screening. Analyses have demonstrated temporalchanges in breast cancer mortality after the introduction of mammo-graphic screening and have inferred that much of this change is dueto the impact of screening.9,11,28 Previous publications usingSMPBC data have shown that women participating in screening arediagnosed with smaller tumors and survive longer.15 However, find-ings from observational studies are subject to potential bias associ-ated with self-selection of screening by the study subjects. A reviewcomparing the results from randomized trials and observationalstudies in 5 areas of medicine, including screening mammography,concluded that well-designed observational studies did not system-atically overestimate the magnitude of treatment effects.29 Also,observational studies based on screening use estimate efficacy whilerandomized population based trials estimate effectiveness.30 Adjust-ing for compliance in randomized trials generally increases theeffect size of screening.31 The results presented in this paper areconsistent with those reported from case-control studies.30

The magnitude of the benefit estimated in this study is depend-ent upon the appropriateness of the incidence and survival ratesused in the calculation of expected mortality. It was assumed thatwomen who chose to participate had the same risk of developingbreast cancer as those who did not. This was supported by the ob-servation that nonparticipants in SMPBC had very similar breastcancer incidence rates to that of the total population prior to thecreation of SMPBC. However, incidence rates in British Columbiawomen under age 40, where screening is uncommon, havedeclined by approximately one half of 1% per year over the studyperiod. If a similar decline in breast cancer risk had occurred inscreened women over the age of 40, then the calculation ofexpected mortality presented in Table III and Figure 3 would beapproximately 5% too high. An inaccuracy of this magnitude doesnot substantially effect the conclusions of the analysis. Incidencerates would have had to decline by an average of 40% in the studyperiod to reduce the measured effect to zero.

Assuming that survival rates of nonparticipants are appropriatefor participants, in they had not been screened, is more problematic.This analysis found that income level of region of residence influ-enced survival and it was adjusted for in the analysis of mortality.However, participation in screening is influenced by personal healthperception and other factors that may have effect independent ofsocioeconomic status. Previous research in the UK has found thatbreast cancer mortality was 17% higher among women offered butnonparticipating in screening than it was in a similar base populationnot offered screening.31 From the participation rate in the UK study(71%) and the reasoning contained in the paper by Duffy et al.,32

the expected breast cancer mortality ratio of nonparticipants to par-ticipants can be calculated, which yields a ratio of 1.26. If this mor-tality ratio applies to the data in this study, it would imply that theexpected mortality calculated is 26% too high so that the breast mor-tality ratio associated with screening would be 0.76 (0.603 1.26).

Clinical trials of screening have employed standardized meth-ods to assess cause of death to accurately identify women who diefrom breast cancer. This study relied on the death certificate causeof death as the outcome. While this is likely to contain some inac-curacy, it seems unlikely that this would result in any biasedassessment in favor of screened women since both screened andunscreened women receive care through a common medical sys-tem. Outcomes among SMPBC participants could also be im-proved if they received superior treatment to nonparticipants. Pre-vious publications have found breast cancer treatment patterns inBritish Columbia women to show a high degree of consistencyduring the study period33,34 so that a large effect is unlikely.Although it can be argued that modern systemic therapy may haveeroded the value of breast screening,14 large differences still per-sist in prognosis by extent of disease at diagnosis.35 In fact, duringthe study period, metastatic breast cancer remained essentially in-curable while survival from early stage cancer improved.35

It appears that the majority of the mortality reduction seen inwomen participating in the SMPBC is due to the effect of mam-mography screening and that it is shared by all women over age40. The results for women aged 40–49 contrasts with findings of aCanadian trial conducted in the same age group that found no mor-tality reduction.5 However, the results presented here for agegroup 40–49 are compatible with reviews of trial results2,23,24 forthis age group after allowance of a 26% mortality advantage dueto self-selection. The absolute benefit of screening for womenaged 40–49 is less because the risk of breast cancer, and subse-quent death, is lower than for older women. However, their lifeexpectancy is higher, so that more years of life are potentiallysaved for every death prevented.

Acknowledgements

The authors acknowledge the helpful comments from the re-viewers and associate editor, which substantially improved thequality of this manuscript.

FIGURE 3 – Observed and expected cumulative mortality rates inwomen participating in SMPBC between 1988–2003 between the agesof 40–49 at first screen, including all breast cancer deaths and includingonly deaths in women in whom there was a diagnosis prior to age 50.

1079BREAST CANCER MORTALITY AFTER SCREENING

References

1. Kerlikowske K, Grady D, Rubin S, Sandrock C, Ernster V. Efficacy ofscreening mammography: a meta analysis. JAMA 1995;273:149–54.

2. Vainio H, Bianchini F, eds. IARC Handbooks of cancer prevention,vol. 7: Breast cancer screening. Lyon: IARC Press, 2002.

3. Ringash J. Canadian Task Force on Preventive Health Care. Preventivehealth care, 2001 update: screening mammography among women aged40–49 years at average risk of breast cancer. Can Med Assoc J 2001;164:469–76.

4. Tabar L, Faberberg G, Day N, Holmberg L. What is the optimum inter-val between mammographic screening examinations? An analysisbased on the latest results of the Swedish two-county breast cancerscreening trial. Br J Cancer 1987;55:547–51.

5. Miller A, To T, Baines C, Wall C. The Canadian Breast ScreeningStudy-1: breast cancer mortality after 11–16 years of follow-up. Arandomized screening trial of mammography in women aged 40–49years. Ann Intern Med 2002;137:305–12.

6. Miller A, To T, Baines C, Wall C. Canadian National Breast Screen-ing Study-2: 13 year results of a randomized trial in women aged 50–59 years. J Natl Cancer Inst 2000;92:1490–9.

7. Moss S. A trial to study the effect on breast cancer mortality of annualmammographic screening in women starting at age 40. Trial steeringgroup. J Med Screen 1999;6:144–8.

8. Breast screening frequency trial group. The frequency of breast cancerscreening: results from the UKCCCR randomized trial. Eur J Cancer2002;38:1458–64.

9. Paci E, Duffy S, Giorgi D, Crocetti E, Vezzosi V, Bianchi S, Rosellidel Turco M. Quantification of the effect of mammographic screeningon fatal breast cancers: the Florence programme 1990–96. Br J Cancer2002;87:65–9.

10. Tabar L, Yen M, Vitak B, Chen H, Smith R, Duffy S. Mammographyservice screening and mortality in breast cancer patients: 20 year fol-low-up before and after introduction of screening. Lancet 2003;361:1405–10.

11. Otto S, Fracheboud J, Looman C, Broeders M, Boer R, Hendriks J,Verbeek A, de Koning H. National Evaluation Team for Breast Can-cer Screening. Initiation of population based mammography screeningin Dutch municipalities and effect on breast-cancer mortality: a sys-tematic review. Lancet 2003;361:1411–17.

12. Jonsson H, Tornberg S, Nystrom L, Lenner P. Service screening withmammography in Sweden. Acta Oncol 2000;39:617–23.

13. Berry D, Cronin K, Plevritis S, Fryback D, Clarke L, Zelen M,Mandelblatt J, Yakovlev A, Habbema J, Feuer E. Effect of screeningand adjuvant therapy on mortality from breast cancer. N Engl J Med2005;353:1784–92.

14. Jatoi I, Miller A. Why is breast cancer mortality declining. LancetOncol 2003;4:251–4.

15. Olivotto I, Kan L, d’Yachkova Y, Burhenne LW, Hayes M, Hislop T,Worth A, Basco V, King S. Ten years of breast screening in thescreening mammography program of British Columbia, 1988–97.J Med Screen 2000;7:152–9.

16. Burhenne LW. The economics of screening mammography: cost con-tainment methods in the screening mammography program of BritishColumbia. Semin Breast Dis 2001;4:36–44.

17. Jaro M. Probabilistic linkage of large public health data files. StatMed 1995;14:491–8.

18. Sasieni P. On the expected number of cancer deaths during follow-upof an initially cancer-free cohort. Epidemiology 2003;14:108–10.

19. McCullagh P, Nelder J. Generalized linear models, 2nd edn. London:Chapman and Hall, 1989. Monographs on statistics and applied proba-bility (Cox D et al., eds.), vol.37., 194–8.

20. Lawless J. Statistical models and methods for lifetime data. New York:Wiley, 1982.

21. Tetrad. P Census with ESRI mapping users guide. Vanc ouver: TetradComputer Applications, 2001. Canadian edition.

22. BC Cancer Agency. Screening Mammography Program of BC 2001/2002 Annual Report. Vancouver: BC Cancer Agency, 2002.34p.

23. Hendrick R, Smith R, Rutledge J, Smart C. Benefit of screening mam-mography in women aged 40–49: a new meta-analysis of randomizedcontrolled trials. J Natl Cancer Inst Monogr 1997;22:87–92.

24. Nystrom L, Andersson I, Bjurstam N, Nordenskjold B, Rutqvist L.Long term effects of mammography screening: updated overview ofthe Swedish randomised trials. Lancet 2002;359:909–19.

25. de Koning H, Boer R, Warmerdam P, Beemsterboer P, van der Maas P.Quantitative interpretation of age-specific mortality reductions from theSwedish breast cancer-screening trials. J Natl Cancer Inst 1995;87:1217–23.

26. Larsson L-G, Andersson I, Bjurstam N, Faberberg G, Frisell J, Tabar L,Nystrom L. Updated overview of the Swedish randomized trials onbreast cancer screening with mammography: age group 40–49 at ran-domization. Monogr Natl Cancer Inst 1997;22:57–61.

27. Smith R. Breast cancer screening among women younger than age 50:a current assessment of the issues. CA Cancer J Clin 2000;50:312–36.

28. Tabar L, Vitak B, Hsui-Hsi T, Ming-Fang Y, Duffy S, Smith R.Beyond randomized control trials: organized mammographic screen-ing substantially reduces breast carcinoma mortality. Cancer 2001;91:1724–31.

29. Concato J, Shah N, Horwitz R. Randomized controlled trials, observatio-nal studies and the hierarchy of research designs. N Engl J Med 2000;342:1987–92.

30. Walter S. Mammographic screening: case-control studies. Ann Oncol2003;14:1190–92.

31. Moss S, Summerley M, Thomas B, Ellman R, Chamberlain J. A case-control evaluation of the effect of breast cancer screening in theUnited Kingdom trial of early detection of breast cancer. J EpidemiolCommunity Health 1992;46:362–4.

32. Duffy S, Cuzick J, Tabar L, Vitak B, Chen H, Yen M, Smith R. Cor-recting for non-compliance bias in case-control studies to evaluatecancer screening programmes. Appl Stat 2002;51:235–43.

33. Goel V, Olivotto I, Hislop T, Sawka C, Coldman A, Holowaty E.Patterns of initial management of node-negative breast cancer in twoCanadian provinces. British Columbia/Ontario Working Group. CanMed Assoc J 1997;156:25–35.

34. Sawka C, Olivotto I, Coldman A, Goel V, Holowaty E, Hislop T. Theassociation between population-based treatment guidelines and adju-vant therapy for node-negative breast cancer. British Columbia/On-tario Working Group. Br J Cancer 1997;75:1534–42.

35. Winer E, Morrow M, Osbourne C, Harris J. Malignant tumors of thebreast. In: DeVita V, Hellman S, Rosenberg S, eds. Cancer: Principlesand practice of oncology. Philadelphia: Lippincott, Williams andWilkins, 2001. 1651–1717.

1080 COLDMAN ET AL.