The American Journal of Medicine

1

Mammography screening among the elderly: A research challenge

Maureen Sanderson PhD a Robert S Levine MD a Mary K Fadden MPH a

Ba

a Depar N 37208

b Divisi L 37232

c Cente

d Depar Knox

e Depar

f Depar Texas

g Moreh A

h Charl 31, USA

Running t

Correspon Meharry M 1-615-321-2

Abstract w Number o Number o Conflict of interest for all authors: None All authors had access to the data and a role in writing the manuscript.

2

Abstract Background: Randomized trials demonstrate clear benefits of mammography screening in

women through age 74 years We explored age- and race-specific rates of mammography

screening

Methods:

Epidemio

Hispanic es

diagnosed

mammog st

cancer mo

Results: A

condition

intervals)

women ag r

biennial m r

biennial m

stratified

Conclusio

selected f ng

women w re

similar am

used for current screening mammography recommendations.

Keywords: Breast cancer screening, mortality, racial disparity, geographic disparities

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Introduction

Randomized trials demonstrate clear benefits of mammography screening in women up

to age 74 years 1 After age 74 there are no cogent data from randomized trials 1 Data from

minority p

(SEER) p

screening er

mortality ual

or biennia

5

Materials and Methods

Detailed methods of the SEER-Medicare linked file are previously published.2 The SEER

program, comprised of 17 highly qualified cancer registries reflecting 26% of the US population,

includes d

health ins nd

women ag

were succ R

registries S

Census B

A

1995 thro

was chose he

exposure

preceding

irregular m

female, n A

and B cov re

not provid

Hispanics

non-Hisp

Smith-Bin

mammograms.

6

The women were categorized into three mutually exclusive age groups at breast cancer

diagnosis: (Group 1) women ages 69-74 years since the American Cancer Society (ACS)8 and

the United States Preventive Services Task Force (USPSTF)1 recommend regular mammography

for wome

cleanly in d

USPSTF up.

Th

women di

persons w .

Exclusion

diagnoses

diagnosed

Committe

Medicare

(n=17,618

detecting

between t

(n=17,236 7;

Group 3, 7 f

breast can

ages 69-8 r-

years pre-diagnosis while stratifying by race and controlling for confounding factors.9 Cause of

death was available from the SEER file. Survival time was calculated in months from the date of

7

diagnosis to the date of death or the date of last follow-up (December 31, 2010, indicated in the

Medicare file). Cases lost to follow-up, those still alive at the end of the follow-up period, or

those who died of causes other than breast cancer were censored No assumptions were made

about the

Kaplan-M

Si ng

on breast

and AJCC

hazards m as

no eviden

confound sis

year, urba

condition es

made or p

elsewhere

status, we

informati el,

and the pe

separately

radiation

screening

status were retained for confounding adjustment to conform to other analyses.

8

Results

Tables 1 and 2 compare the demographic characteristics of non-Hispanic white and black

women who died of breast cancer with those who were alive or censored at 5 years post

diagnosis er,

have a lat

economic ive

radiation

women. A wn)

did not su

Ta

for 5-year ed

for AJCC

economic

referent g ve

to no/irre s

(Table 3) 43-

0.58), 0.4 e

4) they w -

0.66), 0.4 ar,

biennial, ,

correspon 7

(0.44-0.51) for biennial mammography among whites and 0.36 (0.29-0.44) for annual and 0.47

(0.37-0.58) for biennial mammography among blacks. Tests for trend were again highly

significant.

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Conclusions

In these data, 69 to 84 year old women receiving regular annual screening mammography

during the four years immediately preceding breast cancer diagnosis had consistently lower five-

year and t

regardles ng

blacks ag

associatio y,

chemothe

Tw s

for screen

that in the r

screening

schedule. d.16

The USPS

adds that CS

and USPS

mammog

mammog

observatio

A s

of ongoin

University of Michigan18 and a six-county mobile van program at the University of California

San Francisco19). Neither is representative of the US. Also, in each study, the end points focused

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on tumor size at detection,18,19 which may lead to more conservative estimates (i.e.,

underestimates) of benefit.20 In the University of Michigan study,18 a retrospective record review

of women ages 65 years and older (1988 to 1995) the proportion of patients who presented with

a palpable

(48%) tha

proportio p

with the s co

study (19 s

27% smal hy

was assoc re

reduced, a er

biopsy co

annual gr of

tumor cha

attendanc

contrast to

determine ad

been regu

Th ity

of data am

observatio

primary endpoint was breast cancer mortality. Limitations of the predictive models include

reliance on self-reported mammography and national cohorts. Specifically, mammography self-

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report overestimates use26 and underestimates disparities,26, 27 while the use of national

cohorts23,25 may obscure variations in potential benefit among demographic and geographic sub-

populations For example differences in mortality according to geographical area of residence

and amon

considers

A g to

frequency

biennial s

United Ki r

study33 co

interval fo

screens ov n

contrast, t

biennial s

that study at

greater cl

A

percentag

irregular,

(2002-200

positives)

mammography (2.5%) which would not have occurred with biennial screening. Among blacks,

there were 35 biopsies among the 1,277 women receiving annual mammography (2.7%) which

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would not have occurred with biennial screening. The net increase for annual screening was

therefore 323 biopsies among the 54,213 women receiving either annual or biennial

mammography (0 6%)

A

data from y

utilization t

for bienni

annual sc

can be us

US, it is u

Linking th a

are also s F1)

as the exp

mammog

Li

underestim e

US. SEER

since 199 in

these data es

such as le

(screening

screening may be healthier and may have a variety of social advantages).16 Further, it has been

estimated that the lag time between the start of screening and onset of mortality benefits may be

13

at least 10 years.17 Nonetheless, the better 10-year survival associated with annual

mammography in these data lessens the probability that observed benefits are solely due to lead

time bias. Similarly the observation of benefits independent from AJCC stage radiation therapy,

and chem at

the time o

independe ue

to the fac

adjustmen

reflect be

which the

status, SE

consisten

promising

In

accounted

believe th in

this popu

reflected od

of greater d

ethnic mi r

2030.3 W

biennial mammography would be hampered by high costs and feasibility issues, this design

strategy would provide the most reliable means to assess the most plausible way to discriminate

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small to moderate differences. In the interim, the present results highlight the evidentiary

limitations of data used for current screening mammography recommendations.

15

Acknowledgements

This study was supported in part by a grant from the National Institute of Minority Health

and Health Disparities (grant P20 MD000516).

16

References

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Services Task Force Recommendation Statement Ann Intern Med 2009 ;151(10) :716-

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16. Walter LC, Schonberg MA. Screening mammography in older women: A review. JAMA

2014; 311(13): 1336-1347.

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17. Braithwaite D, Mandelblatt JS, Kerlikowske K. To screen or not to screen older women

for breast cancer: A conundrum. Future Oncol 2013; 9(6): 763-766.

18. Field LR Wilson TE Strawderman M et al Mammographic screening in women more

th 8;

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v J

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2013; 105(5): 334-341.

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25. Mandelblatt JS, Cronin KA, Bailey S, et al. Effects of mammography screening under

different screening schedules: Model estimates of potential benefits and harms. Ann

Intern Med 2009; 151(10): 738-747

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w

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re

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January 2013. Data are compiled from Compressed Mortality File 1999-2011 Series 20

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No. 2P, 2013. Accessed at http://wonder.cdc.gov/cmf-icd10.html on May 12, 2014

6:13:22 AM

33. Hennekens CH DeMets D Statistical association and causation: Contributions of

d

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fr

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a 9;

2

37. H due

e

2

Table 1. Demographic characteristics of white women age 69-74 diagnosed with primary non-metastatic breast cancer who did and did not die from breast cancer by time period Dead (n=2,407) Alive or Censored (n=22,289) Characteristic n % n % Age (years) 66-69 5.9 70-74 4.1 Diagnosis 1995-19 9.3 1998-20 4.9 2001-20 4.1 2004-20 1.7Urban/Rur Big met 1.9 Metro 9.5 Urban/le 8.6 AJCC stag In Situ/I 2.9 II 0.3 III 1.9 Unstage 4.9 Surgery Yes 7.5 No/Unk 2.5 Radiation Yes 7.7 No 9.8 Unknow 2.5Chemothe Yes 7.2 No 8.7 Unknow 4.0 Charlson i 0 8.4 1 7.5 ≥2 7.3 Unknow 6.8 Contextua Quartile 6.3 Quartile 4.8 Quartile 4.7 Quartile 4.2

Table 2. Demographic characteristics of black women ages 69-74 diagnosed with primary non-metastatic breast cancer who did and did not die from breast cancer Dead (n=335) Alive or Censored (n=1,831) Characteristic n % n % Age (years) 66-69 7.1 70-74 2.9 Diagnosis 1995-19 6.0 1998-20 2.2 2001-20 5.9 2004-20 5.9Urban/Rur Big metr 7.3 Metro 2.4 Urban/le 0.3 AJCC stag In Situ/I 4.8 II 2.8 III 3.3 Unstage 9.1 Surgery Yes 5.3 No/Unk 4.7 Radiation Yes 9.7 No 7.4 Unknow 2.9Chemothe Yes 0.2 No 5.3 Unknow 4.5 Charlson i 0 0.3 1 5.7 ≥2 6.9 Unknow 7.1 Contextua Quartile 5.7 Quartile 4.8 Quartile 5.1 Quartile 4.4

Table 3. Hazard ratios of 5-year breast cancer mortality associated with mammography screening among non-Hispanic white women: (a) ages 69-74; (b) ages 75-78; and (c) ages 79-84 years

(a) 69-74 years (Group 1) Dead (n=1,569)

Alive or Censored (n=23,127)

n % N % HRa 95% CIb Mammogr No/Irreg ) Biennial 58) Annual 3) p-value fo

(b) 75

Ib Mammogr No/Irreg ) Biennial 55) Annual 2) p-value fo

(c) 79

Ib Mammogr No/Irreg ) Biennial 45) Annual 3) p-value fo aHazard ra contextual b95% Con

Table 4. Hazard ratios of 5-year breast cancer mortality associated with mammography screening among non-Hispanic black women: (a) ages 69-74; (b) ages 75-78; and (c) ages 79-84 years

(a) 69-74 years (Group 1) Dead (n=258)

Alive or Censored (n=1,908)

N %

n % n % HRa 95% CIb Mammogr No/Irreg ) Biennial 66) Annual 57) p-value fo

(b) 75

Ib

Mammogr No/Irreg ) Biennial 72) Annual 8) p-value fo

(c) 79

Ib Mammogr No/Irreg ) Biennial 72) Annual 56) p-value fo aHazard ra contextual b95% Con

Table 5. Hazard ratios of 10-year breast cancer mortality associated with mammography screening among non-Hispanic white women and black women age 69-84 years

White women

Dead (n=6,303)

Alive or Censored (n=53,195)

n % n % HRa 95% CIb Mammogr No/Irreg ) Biennial 51) Annual 3) p-value fo

Bl

Ib Mammogr No/Irreg ) Biennial 58) Annual 44) p-value fo aHazard ra contextual b95% Con

Clinical Significance

• Black and white women ages 75 to 84 years who had annual mammography had lower ten year breast cancer mortality than corresponding women who had biennial or no