Screening Mammography - Marquette

Screening Mammography
Policy and Politics

Kevin L. Piggott, MD, MPH
August 29, 2015
Objectives
1. To review the current recommendations
for screening mammography by various
national groups
2. To provide a historical context to
screening mammography
recommendations
3. To review data from major studies on
screening mammography from which
recommendations were generated
4. To aid the practicing clinician in
reconciling the various recommendations
Screening mammography (in
average risk women)
• This is not about diagnostic
mammography
• Well studied
– Ten major randomized trials
– ~600,000 patients
– Followed over 10 yrs
• Very contentious (and has been for
decades)
• How “early” is too early? When does it
make a difference? Is the implication of the
statement “if only you had just come in a
little earlier……,” true?
Epidemiology
• 220,000 women were diagnosed with
breast CA in 2011
• ~41,000 deaths in 2011
U.S. Cancer Statistics Working Group. United States Cancer
Statistics: 1999–2011 Incidence and Mortality Web-based Report.
Atlanta: U.S. Department of Health and Human Services, Centers
for Disease Control and Prevention and National Cancer Institute;
2014. Available at:www.cdc.gov/uscs.
Age-Adjusted Invasive Cancer Incidence
Rates for the 10 Primary Sites with the
Highest Rates
U.S. Cancer Statistics Working Group. United States Cancer
Statistics: 1999–2011 Incidence and Mortality Web-based Report.
Atlanta: U.S. Department of Health and Human Services, Centers
for Disease Control and Prevention and National Cancer Institute;
2014. Available at:www.cdc.gov/uscs.
Age-Adjusted Cancer Death Rates for the
10 Primary Sites with the Highest Rates
U.S. Cancer Statistics Working Group. United States Cancer
Statistics: 1999–2011 Incidence and Mortality Web-based Report.
Atlanta: U.S. Department of Health and Human Services, Centers
for Disease Control and Prevention and National Cancer Institute;
2014. Available at:www.cdc.gov/uscs.
Chances of the Development of and Death from Breast
Cancer within the Next 10 Years.
Fletcher SW, Elmore JG. N Engl J Med 2003;348:1672-1680.
Recommendations
USPSTF – Nov 2009
Screening for Breast Cancer Using Film Mammography
Population
Women aged 40-49 years
Women aged 50-74 years
Recommendation Individualize decision to begin
Screen every 2 years.
biennial screening according to the
patient's circumstances and values. Grade:
Women aged ≥75 years
No recommendation.
Grade:
(Insufficient Evidence)
Grade:
A single, large comparison study of film and digital mammography (18)
demonstrated similar diagnostic accuracy for the 2 methods, although digital
mammography was better at detecting lesions in women who were younger
than 50 years or premenopausal or had radiographically dense breasts.
Pisano ED, Gatsonis C, Hendrick E, Yaffe M, Baum JK, Acharyya S, et al;
Digital Mammographic Imaging Screening Trial (DMIST) Investigators
Group. Diagnostic performance of digital versus film mammography for breastcancer
screening. N Engl J Med. 2005;353:1773-83.
USPSTF http://www.uspreventiveservicestaskforce.org/Page/Name/understanding-how-theuspstf-works
Grade
Definition
Suggestions for Practice
A
The USPSTF recommends the service.
Offer or provide this service.
There is high certainty that the net benefit is
substantial.
B
The USPSTF recommends the service.
Offer or provide this service.
There is high certainty that the net benefit is
moderate or there is moderate certainty that
the net benefit is moderate to substantial.
C
The USPSTF recommends selectively
offering or providing this service to
individual patients based on professional
judgment and patient preferences. There is
at least moderate certainty that the net
benefit is small.
D
The USPSTF recommends against the
Discourage the use of this service.
service. There is moderate or high certainty
that the service has no net benefit or that
the harms outweigh the benefits.
The USPSTF concludes that the current
I
Statement evidence is insufficient to assess the
Offer or provide this service for selected patients
depending on individual circumstances.
Read the clinical considerations section of
USPSTF Recommendation Statement. If the
balance of benefits and harms of the
service is offered, patients should understand the
service. Evidence is lacking, of poor quality, uncertainty about the balance of benefits and
or conflicting, and the balance of benefits
harms.
and harms cannot be determined.
USPSTF 2015 Draft: Recommendation Summary
•This recommendation applies to asymptomatic women age 40 years and older who do not have pre-existing breast cancer or a previously diagnosed high-risk breast lesion and
who are not at high risk for breast cancer because of a known underlying genetic mutation (such as a BRCA mutation or other familial breast cancer syndrome) or a history of chest
radiation at a young age.
Grade
(What's This?)
Population
Recommendation
Women ages 50 to 74 years
The USPSTF recommends biennial screening mammography for women ages 50 to 74 years.
Women ages 40 to 49 years
The decision to start screening mammography in women prior to age 50 years should be an
individual one. Women who place a higher value on the potential benefit than the potential
harms may choose to begin biennial screening between the ages of 40 and 49 years.
•For women at average risk for breast cancer, most of the benefit of mammography will result
from biennial screening during ages 50 to 74 years. Of all age groups, women ages 60 to 69
years are most likely to avoid a breast cancer death through mammography screening.
Screening mammography in women ages 40 to 49 years may reduce the risk of dying of breast The USPSTF recommends against
cancer, but the number of deaths averted is much smaller than in older women and the number routinely providing the service. There may
of false-positive tests and unnecessary biopsies are larger.
be considerations that support providing
•All women undergoing regular screening mammography are at risk for the diagnosis and
the service in an individual patient. There is
treatment of noninvasive and invasive breast cancer that would otherwise not have become a
at least moderate certainty that the net
threat to her health, or even apparent, during her lifetime (known as “overdiagnosis”). This risk benefit is small.
is predicted to be increased when beginning regular mammography before age 50 years.
•Women with a parent, sibling, or child with breast cancer may benefit more than average-risk
women from beginning screening between the ages of 40 and 49 years.
Women age 75 years and older
The USPSTF concludes that the current evidence is insufficient to assess the balance of
benefits and harms of screening mammography in women age 75 years and older.
All women
The USPSTF concludes that the current evidence is insufficient to assess the benefits and
harms of tomosynthesis (3-D mammography) as a screening modality for breast cancer.
Women with dense breasts
The USPSTF concludes that the current evidence is insufficient to assess the balance of
benefits and harms of adjunctive screening for breast cancer using breast ultrasound, magnetic
resonance imaging (MRI), tomosynthesis, or other modalities in women identified to have dense
breasts on an otherwise negative screening mammogram.
The USPSTF recommends the service. There is
high certainty that the net benefit is moderate or
there is moderate certainty that the net benefit is
moderate to substantial.
The USPSTF concludes that the current
evidence is insufficient to assess the balance of
benefits and harms of the service. Evidence is
lacking, of poor quality, or conflicting, and the
balance of benefits and harms cannot be
determined.
American Cancer Society*;
• Women age 40 and older should have a
mammogram every year and should continue to
do so for as long as they are in good health.
• http://www.cancer.org/healthy/findcancere
arly/cancerscreeningguidelines/americancancer-society-guidelines-for-the-earlydetection-of-cancer
*At one time, the ACS used to run an ad stating, “If a
woman doesn‘t have a mammogram, she needs more
than her breasts examined”
ACOG;
Based on the incidence of breast cancer, the
sojourn time for breast cancer growth, and the
potential reduction in breast cancer mortality,
the College recommends that women aged 40
years and older be offered screening
mammography annually.
American College of Radiology;
• For average-risk women, annual screening
mammography is indicated starting at age 40.
National Cancer Institute;
Women age 40 years and older should have
mammography every 1-2 years.
http://www.cancer.gov/cancertopics/pdq/screen
ing/breast/healthprofessional
National Comprehensive Cancer Network;
Women age 40 years and older should have
mammography annually
Huh? What to recommend?
• There is a delicate balance between
benefit and harm
• Reasonable clinicians and patients may
come to different conclusions even when
presented the same scenario
• Thus, it is imperative to have a discussion
with your patients.
Benefit Assumption #1
• Being screened regularly for breast cancer
will reduce a woman’s risk of dying from
breast cancer
The HIP study - 1963
•
•
•
Health Ins Plan of NY with the National Cancer
Institute (NCI)
Population - 62,000 women aged 40-64 in
randomized study
Intervention – annual mammogram and clinical breast
exam; control group received neither
– Therefore could not isolate benefit of mammogram alone
– Also there was an increased awareness to early treatment
of breast CA
•
By the end of 18 years from entry,
– the study group had about a 25% lower breast cancer
mortality among women aged 40-49 and 50-59 at time of
entry than did the control group.
• However, to a large extent the difference among the
40-49-year-olds occurred in the subgroup with breast
cancer diagnosed after these women had passed their
50th birthday.
– Therefore, the benefit would likely have been the
same had they initiated mammography screening
at 50 yo.
• Amongst women in their forties when diagnosed with
breast CA, there was no reduction in mortality
1973
• Both the NCI and the American Cancer
Society (ACS) launched a nationwide
effort for screening mammography
– All women age 35 and older were encouraged
to have screening mammography
1976
• Due to concerns regarding radiation
exposure of radiosensitive tissue in young
women, the recommendation was
changed
– women ≥50 were encouraged to have
screening mammograms and no longer
included 35-49 yo
– However, mammography then exposed women
to higher amounts of radiation than now.
1988
• ACS and NCI revise their
recommendations to begin annual
screening mammography at 40
– Mammography equipment had improved with
reduction in radiation
– HIP study re-analyzed and it was felt that
women in their forties do benefit
1992
• Canadian National Breast Screening
Study
– Design similar to HIP study
– Focused only on women 40-49
– Result – Screening mammography did not
reduce deaths from breast cancer
1993
• ACS re-confirms its recommendations to screen
young women
• 9 major studies had been completed by this time
and it remained inconclusive as to the benefit of
screening mammography in women <50 yo.
• NCI convenes an international workshop to
summarize the trials (not to make
recommendations)
– Conclusion
• “For women aged 40–49, randomized controlled
trials of breast cancer screening show no benefit 5–
7 years after entry. At 10–12 years, benefit is
uncertain and, if present, marginal; thereafter, it is
unknown. For women aged 50–69, screening
reduces breast cancer mortality by about a third.
Currently available data for women age 70 or older
are inadequate to judge the effectiveness of
screening”
1997
• The Director of the NCI convened a 13
member panel to make a consensus
recommendation
• Conclusion
– “The data currently available do not warrant a
universal recommendation for mammography
for all women in their forties. Each woman
should decide for herself whether to undergo
mammography. . . . Given both the importance
and complexity of the issues involved in
assessing the evidence, a woman should have
access to the best possible relevant information
regarding both benefits and risks, presented in
an understandable and usable form.”
1997
Suzanne Fletcher, MD 336 (16); 1180-1183
USPSTF - 2002
Summary of Recommendations
“The U.S. Preventive Services Task
Force (USPSTF) recommends
screening mammography, with or
without clinical breast examination
(CBE), every 1-2 years for women
aged 40 and older.
The USPSTF recommends the
service. There is high certainty that the
net benefit is moderate or there is
moderate certainty that the net benefit
is moderate to substantial.”
USPSTF - 2009
Summary of Recommendations
“The USPSTF recommends against routine
screening mammography in women aged 40 to 49
years. The decision to start regular, biennial
screening mammography before the age of 50
years should be an individual one and take into
account patient context, including the patient’s
values regarding specific benefits and harms.
(Grade C recommendation)”
USPSTF - 2009
USPSTF - 2009
From: A Systematic Assessment of Benefits and Risks to Guide Breast Cancer Screening Decisions
JAMA. 2014;311(13):1327-1335. doi:10.1001/jama.2014.1398
Table Title:
Pooled Results from Randomized Clinical Trials on Mortality Reductions With Mammography Screening by Age Group
Date of download: 8/24/2015
Copyright © 2015 American Medical
Association. All rights reserved.
USPSTF - 2009
40-49
Pos
Neg
Breast CA Breast CA
26
978
Pos Mamm
10
10,000
Spec =
2.6%
NPV=
99.9%
8986
Neg Mamm
Sens =
PPV=
72.2%
90.2%
Pos Breast CA = invasive CA and DCIS
50-59
Pos
Neg
Breast CA Breast CA
47
866
Pos Mamm
11
10,000
Spec =
5.1%
NPV=
99.9%
9076
Neg Mamm
Sens =
PPV=
81.0%
91.3%
Pos Breast CA = invasive CA and DCIS
60-69
Pos
Neg
Breast CA Breast CA
65
790
Pos Mamm
14
10,000
Spec =
7.6%
NPV=
99.8%
9131
Neg Mamm
Sens =
PPV=
82.3%
92.0%
Pos Breast CA = invasive CA and DCIS
70-79
Pos
Neg
Breast CA Breast CA
79
688
Pos Mamm
15
10,000
Spec =
10.3%
NPV=
99.8%
9218
Neg Mamm
Sens =
PPV=
84.0%
93.1%
Pos Breast CA = invasive CA and DCIS
80-89
Pos
Neg
Breast CA Breast CA
85
594
Pos Mamm
14
10,000
Spec =
12.5%
NPV=
99.8%
9307
Neg Mamm
Sens =
PPV=
85.9%
94.0%
Pos Breast CA = invasive CA and DCIS
Table 3. Estimated Benefits and Harms of Mammography Screening for 10,000
Women Who Undergo Annual Screening Mammography Over a 10-Year Period a
Age, y
No. of Breast
Cancer Deaths
Averted With
Mammography
Screening
Over Next 15 y
b
No. (95% CI) With
≥1 False-Positive
Result During the
10 y c
No. (95% CI)
With ≥1 False
Positive
Resulting in a
Biopsy During
the 10 y c
No. of Breast
Cancers or
DCIS
Diagnosed
During the 10 y
That Would
Never Become
Clinically
Important
(Overdiagnosis)
d
40
1–16
6,130 (5,940–
6,310)
700 (610–780) ?–104 e
50
3–32
6,130 (5,800–
6,470)
940 (740–
1,150)
30–137
60
5–49
4,970 (4,780–
5,150)
980 (840–
1,130)
64–194
No. = number; CI = confidence interval; DCIS = ductal carcinoma in situ.
a Adapted from Pace and Keating.[1]
b Number of deaths averted are from Welch and Passow.[2] The lower bound represents breast
cancer mortality reduction if the breast cancer mortality relative risk were 0.95 (based on minimal
benefit from the Canadian trials [3,4]), and the upper bound represents the breast cancer mortality
reduction if the relative risk were 0.64 (based on the Swedish 2-County Trial [5]).
c False-positive and biopsy estimates and 95% confidence intervals are 10-year cumulative risks
reported in Hubbard et al. [6] and Braithwaite et al.[7]
d Overdiagnosed cases are calculated by Welch and Passow.[2] The lower bound represents
overdiagnosis based on results from the Malmö trial,[8] whereas the upper bound represents the
estimate from Bleyer and Welch.[9]
e The lower-bound estimate for overdiagnosis reported by Welch and Passow [2] came from the
Malmö study.[8] The study did not enroll women younger than 50 years.
Chances of False Positive Mammograms, Need for
Biopsies, and Development of Breast Cancer among
1000 Women Who Undergo Annual Mammography for 10
Years.
Fletcher SW, Elmore JG. N Engl J Med 2003;348:1672-1680.
Chances of Breast-Cancer–Related Outcomes among
1000 Women Who Undergo Annual Mammography for 10
Years.
Fletcher SW, Elmore JG. N Engl J Med 2003;348:1672-1680.
Cochrane review -2012
Screening for breast cancer with mammography.
•
Gøtzsche PC1, Jørgensen KJ.
•
Author information
Abstract
BACKGROUND:
•
A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and
national policies vary.
OBJECTIVES:
•
To assess the effect of screening for breast cancer with mammography on mortality and morbidity.
SEARCH METHODS:
•
We searched PubMed (22 November 2012) and the World Health Organization's International Clinical Trials Registry Platform
(22 November 2012).
SELECTION CRITERIA:
•
Randomised trials comparing mammographic screening with no mammographic screening.
DATA COLLECTION AND ANALYSIS:
•
Two authors independently extracted data. Study authors were contacted for additional information.
MAIN RESULTS:
•
Eight eligible trials were identified. We excluded a trial because the randomization had failed to produce comparable groups.
The eligible trials included 600,000 women in the analyses in the age range 39 to 74 years. Three trials with adequate
randomization did not show a statistically significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90, 95%
confidence interval (CI) 0.79 to 1.02); four trials with suboptimal randomization showed a significant reduction in breast cancer
mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87). We
found that breast cancer mortality was an unreliable outcome that was biased in favor of screening, mainly because of
differential misclassification of cause of death. The trials with adequate randomization did not find an effect of screening on total
cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years
(RR 0.99, 95% CI 0.95 to 1.03).Total numbers of lumpectomies and mastectomies were significantly larger in the screened
groups (RR 1.31, 95% CI 1.22 to 1.42), as were number of mastectomies (RR 1.20, 95% CI 1.08 to 1.32). The use of
radiotherapy was similarly increased whereas there was no difference in the use of chemotherapy (data available in only two
trials).
AUTHORS' CONCLUSIONS:
•
If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis
and overtreatment is at 30%, it means that for every 2000 women invited for screening
throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would
not have been diagnosed if there had not been screening, will be treated unnecessarily.
Furthermore, more than 200 women will experience important psychological distress including
anxiety and uncertainty for years because of false positive findings. To help ensure that the
women are fully informed before they decide whether or not to attend screening, we have
written an evidence-based leaflet for lay people that is available in several languages on
www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer
awareness since the trials were carried out, it is likely that the absolute effect of screening
today is smaller than in the trials. Recent observational studies show more overdiagnosis than
in the trials and very little or no reduction in the incidence of advanced cancers with
screening.
Among 10,000 women screened for 10 yrs, the number who:
Age
Benefit (avoid breast Ca death)
Don't Benefit
40
5
9995
45
7
9993
50
10
9990
55
14
9986
60
17
9983
65
20
9980
70
23
9977
25
20
40
45
15
50
55
10
60
65
5
70
0
Benefit (avoid breast Ca death)
Benefit Assumption # 2
• Mammography reduces the risk of
developing metastatic Breast CA.
– Not specifically addressed in any study
– SEER (Surveillance, Epidemiology and End
Results) registry data shows that 90% of
women that develop metastatic breast CA die of
it
• Thus metastatic breast CA and death are
similar outcomes
Benefit Assumption #3
• Screening mammography will result in the
need for less aggressive treatment if
breast CA is found
– It has actually led to 20% more mastectomies
Harms
• False reassurance
– Some people believe that a negative
mammogram assures that they do not have
breast cancer
• ~25 % (21.2% in the data shown earlier in
2x2 tables) of breast cancers are not
detected by mammography
• In reality, it only reduces the risk that you
have a breast cancer by about 75%
• The test itself is uncomfortable if not
outright painful for some.
Harms (cont.)
•
False positives results
– 11% of screening mammograms are read as abnormal.
• Breast cancer is found in 3% of abnormal
mammograms
– Therefore, ~10.7% are false positive
–
results in additional studies and expense
• Mammograms (spot compression or additional views)
• Ultrasounds
• MRI’s
• Biopsies
– After 10 mammograms, 49% (95% CI of 40 – 64)
will have had a false + leading to needle or open
biopsy (Elmore JG, Barton MB, Moceri VM, Polk S, Arena
PJ, Fletcher SW. Ten-year risk of false positive screening
mammograms and clinical breast examinations. NEJM
1998;338:1089-96)
– In anxiety/distress
Harms (cont.)
• Advancing the time of diagnosis without
influencing the long term outcome
– A mammographically detected CA can be
• A clinically important cancer that is more
curable when found early
• A clinically important cancer that is not more
curable when when found early
– In which case the mammogram is not
beneficial
– The person is just turned into a breast
cancer patient earlier
• An overdiagnosis
– Again not beneficial
– One estimate placed it at 31% of
diagnoses
Bleyer A, Welch HG. N Engl J Med 2012;367:1998-2005.
Welch GW, Schwartz LM, Woloshin S. Over-Diagnosed
Making People Sick in the Pursuit of Health.
Beacon Press 2011
Use of Screening Mammography and Incidence of StageSpecific Breast Cancer in the United States, 1976–2008.
Bleyer A, Welch HG. N Engl J Med 2012;367:1998-2005.
Absolute Change in the Incidence of Stage-Specific Breast Cancer among Women 40 Years of
Age or Older after the Introduction of Screening Mammography.
Bleyer A, Welch HG. N Engl J Med 2012;367:1998-2005
Aschwanden, C. Why I’m Opting
out of Mammography. JAMA Int Med
2015;175(2):164-165.
Michigan Dense Breast Law
HB 4260
•
•
21st state to enact a breast density law
a classic example of where science and political pressure
collide
–
–
•
•
There is no consensus on what constitutes a “dense breast”
There is no consensus on what alternative imaging should be
offered (if any)
Went into effect June 1, 2015
If a patient’s mammogram demonstrates dense breast
tissue, that patient must receive notification that includes the
following verbiage:
“Your mammogram shows that your breast tissue is dense.
Dense breast tissue is very common and is not abnormal.
However, dense breast tissue can make it harder to find cancer
through a mammogram. Also, dense breast tissue may increase
your risk for breast cancer. This information about the result of
your mammogram is given to you to raise your awareness. Use
this information to discuss with your health care provider
whether other supplemental tests in addition to your
mammogram may be appropriate for you, based on your
individual risk. A report of your results was sent to your ordering
physician. If you are self-referred, a report of your results was
sent to you in addition to this summary.”
Recommendations Regarding Breast-Cancer Screening
in Women.
Fletcher SW, Elmore JG. N Engl J Med 2003;348:1672-1680.
U.S. Women's Perceptions of the Effects of
Mammography Screening on Breast-Cancer Mortality as
Compared with the Actual Effects.
Biller-Andorno N, Jüni P. N Engl J Med 2014;370:1965-1967.