Screening MammographyValue vs. Jeopardy

Archie Bleyer, MDableyer@stcharleshealthcare.org

Department of Radiation MedicineKnight Cancer Institute at the Oregon Health & Science University

Chair, Institutional Review Board, St. Charles Health System, Central | Eastern Oregon

What if …

the widely quoted breast cancer risk of one in every 8 women

is actually one in 11

?

What if …

a significant proportion of the reported improvement

in overall breast cancer survival is an artifact of overdiagnosis

?

What if you …

were completing 5 years of tamoxifen after a partial mastectomy and breast irradiation,

coping with premature menopause, and undergoing annual mammograms of the other breast,

you learn that there was a one in three chance

of not having had breast cancer?

Objectives

Convey reaction of ‘professionals’ to the controversy

Explain personal motivation

Review requisites of disease screening

Describe the NEJM report and our replies

Compare overdiagnosis risk with benefit of screening

Annual Incidence of In Situ and Localized Breast Cancer, Age 40+ - Western Washington State

0

50

100

150

200

250

300

1970 1980 1990 2000 2010

Incidence per

100,000 Doubling

UW ACS

Professor Clinical

Oncology1983-1990

Relay for LifeGordon Klatt, MD

1983: Screening Mammography Initiated in Washington

A mammogram is a safe, low-dose X-ray that can detect breast cancer before there’s a lump. In other words, it could save your life and your breast.

If you are a women over 35, be sure to schedule a mammogram. Unless you’re still not convinced of its importance.

In which case, you may need more than your breasts examined.

Find the time.Have a mammogram

Get yourself the chance of a lifetime.

Prerequisite Stage Shift for a Successful Cancer Screening Program

EarlyStage

Cancer

LateStage

Cancer

Incidence Reciprocal Stage Shift

Advent of screening

Incidence per

100,000

Annual Incidence of Colorectal Carcinoma by Extent of Disease at Diagnosis, SEER9

0

20

40

60

80

Age 50+

LocalizedRegional

Distant

LocalizedRegional

Distant0

2

4

1970 1975 1980 1985 1990 1995 2000 2005 2010

Age <50Unscreened

0

5

10Age <40

19761980

19841988

19921996

20002004

2008

Incidence per

100,000

Early Stage

Annual Breast Cancer Incidence, Early- vs. Late-Stage Disease at Diagnosis

Late Stage

Screening Mammography Penetration, U.S.

0%

20%

40%

60%

80%

1976 1980 1984 1988 1992 1996 2000 2004 2008

% Screened (within 2 years)

Age 40+

Number of Mammography

Units in U.S.

2,000

0

6,000

4,000

8,000

10,000

Screening Mammography Penetration, U.S.

0%

20%

40%

60%

80%

1976 1980 1984 1988 1992 1996 2000 2004 2008

19761980

19841988

19921996

20002004

20080

50

100

150

200

250

Incidence per

100,000

Early Stage

Late Stage

Annual Breast Cancer Incidence, Early- vs. Late-Stage Disease at Diagnosis

Number of Mammography

Units in U.S.

2,000

0

6,000

4,000

8,000

10,000

% Screened (within 2 years)

Hormone Replacement Therapy (HRT)

Age 40+

0

50

100

150

200

250Early Stage

Late Stage

19761980

19841988

19921996

20002004

2008

Incidence per

100,000

DCIS

Localized

0

50

100

150

200

250

Late Stage

19761980

19841988

19921996

20002004

2008

Regional

Distant

Age 40+

Survival

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 1 2 3 4 5 6 7 8 9 10

Regional

Distant

Relative Survival by Extent of Late Stage, U.S.Females, Breast Cancer, Age 40+

Diagnosed during 2000-2009

Years

1980

1995 2000 20051990

90,000

80,000

70,000

60,000

50,000

40,000

30,000

0

-10,000

-20,000

10,000

Best Guess

Best Guess

Number of Women

Diagnosed with

Breast Cancer

Cumulative Number of Females Diagnosed with Early- and Late-Stage Breast Cancer since 1979, Age 40+, SEER9

1.37 MAdvent of screening

mammography

1995 2000 20051990

Very Extreme Assumption

Very Extreme Assumption

1.02 MOverdiagnosis

Estimate

0.25 %/Year Best Guess

0.5 %/Year

Extreme and Very Extreme Assumption

Early-Stage

Late-Stage

22%

Very Extreme Assumption

+53,000

Very Extreme Assumption

0.5 %/Year

1980

1995 2000 20051990

90,000

80,000

70,000

60,000

50,000

40,000

30,000

0

-10,000

-20,000

10,000

Best Guess

Best Guess

Cumulative Number of Females Diagnosed with Early- and Late-Stage Breast Cancer since 1979, Age 40+, SEER9

Early-Stage+74,000

Advent of screening

mammography

Number of Women

Diagnosed with

Breast Cancer

Overdiagnosis2008

31%

0.25 %/Year

Late-Stage

2004 Zahl2006 Anderson WF, et al.2006 Zackrisson2008 Zahl PH, et al.2009 Jørgensen KJ, et al.2009 Jørgensen KJ, et al.2010 Morrell S, et al.2010 Martinez-Alonso M2012 Hellquist BN, et al.2012 Kalager M, et al.2012 Zahl PH, et al.2012 Puliti D, et al.

Norway and SwedenConnecticut, U.S.Malmö, SwedenFour counties in NorwayDenmarkVariousNew S. Wales, AustraliaCatalonia, SpainTwo counties in SwedenEntire country of NorwaySeven counties in NorwayFlorence, Italy

Overdiagnosis Reported in 12 Prior StudiesNEJM Supplemental Appendix

One-third40%24%**22%33%**

One-third30-42%

47%5%

15-25%**~75%10%

OD Rate

**of screen-detected cancers (other reports are of all breast cancer)

Mean 31.5%

NEJM Correspondence

Stage Migration

Inclusion of DCISUnwarranted Criticism

Background Incidence Increase Assumptions

Overdiagnosis

Estimate

1980

1995 2000 20051990

90,000

80,000

70,000

60,000

50,000

40,000

30,000

20,000

0

-10,000

-20,000

10,000

Best Guess

Best Guess

Number of Women

Diagnosed with

Breast Cancer

Cumulative Number of Females Diagnosed with Early- and Late-Stage Breast Cancer since 1979, Age 40+, SEER9

Late-Stage Cancer

Early-Stage Cancer

Advent of screening

mammography

Radiologist’s Wish1.0%/year increase during 1940-1980 “per” Garfinkel et al (ACS) 1994

Radiologist’s Wish

0.88 M+34,000

Overdiagnosis in 2008

The Treatment and Cost of Breast Cancer Overdiagnosis

• mastectomy or lumpectomy + radiation• anti-hormone therapy for 5-10 years• HER2/neu+: trastuzumab IV q 3 wks x 1 yr• Triple neg: chemotherapyOvertreatment antidotes• Premature menopause: supportive care• Osteopenia: biphosphonate, etc.Cost• Financial, physical, emotional, …

Randomized Trials of Screening Mammography 30 to 50 Years Ago

Trial Country Mortality Benefit Problem(s)

Health Insurance Plan of New York, 1963 U.S. Screening arm included MD Exam

Benefit only in 50-59 y/o’s

Malmo Study Sweden

Two-County Trial Sweden

Gothenburg Breast Screening Trial Sweden

Stockholm Trial Sweden

Edinburgh Trial Scotland

Canadian Natl. Breast Screening Trial 1 Canada None

Actually worse in screened subjects

Canadian Natl. Breast Screening Trial 2 Canada None

Cochrane Analysis

• One biased trial excluded 600,000 women in analyses

• Three trials with adequate randomization did not show a significant reduction in breast cancer mortality at 13 years (RR=0.90, CI 0.79-1.02)

• 4 trials with suboptimal randomization showed a significant reduction in BrCa mortality with an RR=0.75 (CI 0.67-0.83)

• The RR for all 7 trials combined was 0.81 (CI 0.74-0.87)

Cochrane Analysis

• Breast cancer mortality was an unreliable outcome biased in favor of screening, mainly because of differential misclassification of cause of death

• Trials with adequate randomization did not find an effect of screening on cancer mortality:• Either breast cancer, after 10 years

(RR=1.02, 95% CI 0.95-1.10), or• All-cause mortality after 13 years

(RR=0.99, 95% CI 0.95 to 1.03)

Comparison of Old vs. 2009 USPSTF GuidelinesCurrent Average

Lifespan of Oregon’s Females*

44 Mammograms

+Pop Health Metrics 2011,9:16)

35 40 45 50 55 60 65 70 75 80 85Age

13 MammogramsUSPSTF, 2009Heidi Nelson, MD, MPHOHSU

ACS, NCCN, …30+ mSv

To the extent that screening mammograms result in the diagnosis of ‘cancer’ that either does not need to be diagnosed or detected when it is, it can be said that

they cause breast cancer.

How Screening Mammograms ‘Cause’ Breast Cancer(and not from the radiation of mammograms)

These women undergo the same diagnostic interventions and treatment

(including surgery, radiation, and hormonal therapy and in some chemotherapy) and the associated adverse

physical, emotional, and financial effects of women who develop breast cancer without being screened.

“One in every 8 women will develop breast cancer

in her lifetime”

If 31% of all breast cancer is overdiagnosed, the actual risk is one in every 11 women

How much of the reported improvement in overall breast cancer survival is

an artifact of overdiagnosis?

mproved 5-Year Relative Survival of All Breast Cancer (DCIS+ + LRD) Attributable to Overdiagnosis

Survival

Without Overdiagnosis

With Overdiagnosis

• 31% rate of overdiagnosis after 1989• Graded increase of overdiagnosis during 1980s• Assume overdiagnosis to be limited to DCIS

and localized disease at diagnosis 60%

65%

70%

75%

80%

85%

90%

95%

1975 1980 1985 1990 1995 2000 2005

36 Years Ago

We are disappointed by the comments from the leadership of the mammography community.

The first step in addressing any problem is to acknowledge it.

The Big Squeeze A Social and Political History

of the Controversial Mammogram

Handel Reynolds Radiologist MD Atlanta

Aug 7, 2012 Cornell Press

comedsoc.org

http://comedsoc.org/Breast_Cancer_Screening.htm?m=66&s=447