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AJR.17.18707

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Wo m e n ’s I m a g i n g • R ev i ew
Ray et al.
Screening Mammography in Women 40–49 Years Old
FOCUS ON:
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Women’s Imaging
Review
Kimberly M. Ray 1
Bonnie N. Joe1
Rita I. Freimanis1
Edward A. Sickles1
R. Edward Hendrick 2
Ray KM, Joe BN, Freimanis RI, Sickles EA,
­Hendrick RE
Screening Mammography in
Women 40–49 Years Old:
Current Evidence
OBJECTIVE. Breast cancer is an important health problem for women 40–49 years old, yet
screening mammography for this age group remains controversial. This article reviews recent
guidelines and supporting evidence on screening mammography in women of this age group.
CONCLUSION. Evidence supports the benefit of annual screening mammography in
women 40–49 years old. Models of different breast cancer screening strategies consistently
show the greatest breast cancer mortality reduction and life-years gained with annual screening starting when women reach 40 years old.
he incidence of breast cancer in
women in the United States rises
sharply around the age of 40 years
old and increases steadily with
age thereafter. According to 2010–2014 data
from the Surveillance, Epidemiology, and End
Results Program of the National Institutes of
Health, the annual incidence of breast cancer
per 1000 women is 0.3 for women 30–34 years
old, 0.7 for women 35–39 years old, 1.5 for
women 40–44 years old, 2.3 for women 45–49
years old, 2.7 for women 50–54 years old, and
3.2 for women 55–59 years old [1]. In 2015,
breast cancer was diagnosed in 48,160 women
40–49 years old in the United States, which
accounts for approximately one in six breast
cancer diagnoses [2]. It has been estimated that
30% of the years of life lost to breast cancer
occur in women whose disease was diagnosed
when they were 40–49 years old [3].
Several types of evidence on the life-extending benefit of screening mammography
are available for women 40–49 years old.
They include randomized controlled trials
(RCTs), observational studies, and modeling studies [4]. Various organizations have
drawn on these sources of evidence to formulate their screening recommendations. In this
article, we review the evidence, with an emphasis on modeling studies that provide context for critical appraisal of differing screening recommendations.
T
Keywords: mammography, risk, screening
doi.org/10.2214/AJR.17.18707
Received July 1, 2017; accepted after revision
September 5, 2017.
R. E. Hendrick is a consultant to GE Healthcare on work
unrelated to this manuscript.
1
Department of Radiology and Biomedical Imaging,
University of California, San Francisco, 1600 Divisadero
St, Box 1667, C-250, San Francisco, CA 94115. Address
correspondence to B. N. Joe (bonnie.joe@ucsf.edu).
2
Department of Radiology, University of Colorado School
of Medicine, Aurora, CO.
AJR 2018; 210:1–7
0361–803X/18/2102–1
© American Roentgen Ray Society
Randomized Controlled Trials
RCTs provide the most rigorous proof of
the efficacy of screening mammography.
Eight RCTs of screening mammography that
included women 40–49 years old at the time
of trial entry were conducted in the United
States, Europe, and Canada from the 1960s
to 1990s. Meta-analyses of all eight RCTs after 10–18 years of follow-up have shown statistically significant mortality reductions of
15–18% for women who were 40–49 years
old at invitation [5–7]. After 12–14 years of
follow-up of two Swedish trials, statistically
significant mortality reductions of 45% were
found for women who were 39–49 years old
at the time of randomization in the Gothenburg trial and 35% for women who were 45–
49 years old when they entered the Malmö
trial [8–10].
Substantial flaws in the Canadian National Breast Screening Study (CNBSS-1)
of women 40–49 years old have been well
documented [11–13]. Mammography image
quality was judged by experts to be inadequate [14, 15]. Additionally, randomization
was compromised because those responsible
for randomization were not blinded to physical examination results, and significantly
more women with advanced-stage cancers
were allocated to the screening group than
the control group [16]. CNBSS-1 is the only
RCT that found no reduction in breast cancer
mortality in women 40–49 years old; however, its results are unreliable for the reasons
discussed [13, 17]. Excluding the CNBSS-1,
the remaining seven RCTs show a statistically significant 24% mortality reduction for
women who are invited to undergo screening
mammography [7].
AJR:210, February 20181
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Ray et al.
In 1991, the UK Age trial was undertaken to reevaluate the impact of screening
women 40–49 years old. After a median of
10 years of follow-up, investigators reported a statistically significant 25% mortality
reduction, which fell to a 12% mortality reduction at 17.7 years that was not statistically
significant [18]. Limitations of this trial included the performance of single-view mammography, which has been shown to result in
up to 25% of cancers being missed [19]. The
rate of detection of ductal carcinoma in situ
(DCIS) was three times lower than that in the
current United Kingdom national screening
program, suggesting that abnormal microcalcifications were not managed according
to usual screening standards [18].
Although RCTs rigorously establish the
existence of a mortality benefit, they necessarily underestimate the magnitude of mortality reduction from screening because of
study design elements that eliminate bias.
Breast cancer deaths among women randomly assigned to a group of patients who
are invited to undergo screening are attributed to that group whether they participate
in screening or not. Likewise, breast cancer deaths among women assigned to a control group are attributed to that group even
if they participate in screening outside the
trial [20]. These effects cause RCTs to underestimate the magnitude of mortality reduction benefit of screening.
In addition, mammographic technique
has improved markedly since the RCTs were
conducted. Two-view mammography is the
current standard, whereas in the RCTs many
women were screened with one view, which
reduces cancer detection by 20–25% [19].
Screening intervals in the RCTs were relatively long, predominantly ranging from
24 to 33 months, although shorter intervals
yield greater mortality benefit. Finally, as of
June 2017, over 99% of facilities in the United States have digital mammography units
(27% of which are digital tomosynthesis
units) rather than the film-screen units used
in the RCTs [21]. Both digital mammography and tomosynthesis have been documented to have superior cancer detection to filmscreen mammography in younger women
[22–24]. Rafferty et al. [23] reported that the
addition of tomosynthesis to digital mammography produced statistically significant
reductions in recall rates for all age groups,
with the largest reduction in women 40–49
years old (from 13.7% to 11.5%, p < 0.001).
At the same time, the addition of tomosyn-
2
thesis to digital mammography produced a
statistically significant increase in the detection rate of invasive breast cancer, from
1.6 to 2.7 per 1000 women who were 40–49
years old (p < 0.001).
Observational Studies
Because RCTs underestimate the magnitude of screening mammography benefit,
observational studies of population screening programs provide valuable insights into
the effectiveness of screening. Tabar et al.
[25] studied breast cancer mortality rates of
women 40–49 years old in two counties in
Sweden, comparing consecutive 20-year periods before and after the introduction of service screening (1958–1977 and 1978–1997,
respectively). With screening, breast cancer
deaths were reduced by 48% for women 40–
49 years old, which was similar to the 44%
reduction for women 40–69 years old. Coldman et al. [26] documented the outcomes of
over 2.7 million women in seven provincial
service screening programs that served 85%
of Canadian women; from 1990 to 2009,
mortality reduction among screened women
was 44% for women 40–49 years old, which
was similar to the 40%, 42%, and 35% reductions for women 50–59, 60–69, and 70–
79 years old, respectively. An observational
study from the Breast Cancer Surveillance
Consortium (BCSC), a National Cancer Institute–sponsored longitudinal study involving seven regions of the United States, found
that tumors in women 45–49 years old behaved similarly to those in women 50–59
years old and concluded that these groups of
women should be screened similarly [27].
Finally, Hellquist et al. [28] reported on
service screening in Sweden for women 40–
49 years old from 1986 to 2005. After a median 16-year follow-up, breast cancer mortality
rates were 26% lower in counties that invited women to screening than in those that did
not. Because treatments available to women with breast cancer were the same across
Sweden through the nationalized health system, the observed differences in mortality
were due to screening alone.
In summary, because observational studies of service screening mammography reflect actual clinical practice, more current
practice, and larger populations, they overcome some limitations of RCTs. Observational studies have found much greater mortality reductions for women 40–49 years old
than RCTs have. Additionally, observational
studies have found mortality reductions for
women in this age group that were similar to
those for older women [26, 29, 30]. Although
observational studies are subject to selection
bias, the bias does not account for the very
large difference in mortality reduction between observational studies and RCTs.
U.S. Preventive Services Task
Force Controversy
In 2009, the U.S. Preventive Services
Task Force (USPSTF) updated their screening mammography guidelines to recommend
routine screening of women starting at 50
years old. However, they issued a “C” rating
for screening of women 40–49 years old with
average risk of breast cancer, concluding that
the net benefit is small and that the benefits do not outweigh risks as much as is seen
in women 50 years old and older [31]. The
USPSTF relied on the following sources of
evidence in formulating their recommendations: RCT data, age-specific screening outcomes data from the BCSC, and modeling
studies of different screening regimens conducted independently by six different groups
under the Cancer Intervention and Surveillance Modeling Network (CISNET) [32–34].
In their 2009 report, the USPSTF placed little reliance on observational studies of service screening, such as those described in the
previous section, that found greater mortality
reductions than RCTs from screening women 40–49 years old.
On the basis of pooled results of all RCTs,
the USPSTF estimated a breast cancer mortality reduction of 15% for women 40–49
years old, which was similar to a 14% reduction for women 50–59 years old but
substantially lower than the 32% reduction
for women 60–69 years old. Because the
USPSTF included the flawed CNBSS-1 trial and devalued all service screening (observational study) data, the actual mortality reduction benefit for women 40–49 years old
who choose to be screened was substantially underestimated. Based on RCT data alone,
they estimated the numbers needed to invite
(NNI) to screening to prevent one breast cancer death for women 39–49 years old, 50–59
years old, and 60–69 years old to be 1904,
1339, and 377, respectively. They concluded
that an NNI of 1904 for women 40–49 years
old was too high to justify routine screening,
given the risks of anxiety from false-positive
screening recalls as well as anxiety and morbidity from false-positive biopsies.
In 2016, the USPSTF published an update
of their guidelines, addressing concerns
AJR:210, February 2018
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Screening Mammography in Women 40–49 Years Old
raised about their 2009 statement. Based
on this more comprehensive analysis, which
included review of observational studies,
the USPSTF again recommended biennial
screening for women 50–74 years old (“B”
rating) and again assigned a “C” rating for
screening of women 40–49 years old. They
stated that women 40–49 years old should
make individualized decisions regarding
screening, weighing benefits against risks
[35, 36]. In 2016, the USPSTF presented the
balance of benefit versus risk not in terms
of NNI but in terms of false-positive recalls, false-positive biopsies, and overdiagnosis, placing greatest weight on overdiagnosis, which is discussed in greater detail in
a later section.
American Cancer Society Guidelines
In October 2015, the American Cancer Society (ACS) revised their breast cancer screening guidelines, modifying their
2003 unqualified recommendation for annual screening mammography beginning at 40
years old [3]. For women 40–44 years old,
the ACS issued a qualified recommendation
for annual screening mammography, noting
that most women would choose this option.
They issued a strong recommendation for
women 45 years old or older to undergo routine screening mammography.
Citing evidence from the RCTs as well as
observational studies, the ACS noted that
screening mammography yields similar relative mortality reductions but differences
in absolute benefit between women 40–49
years old and those 50–59 years old because
of higher breast cancer incidence with advancing age [5–19, 23–27]. In the United
States, the 5-year incidence of breast cancer
for women 45–49 years old and 50–54 years
old is similar (0.9% vs 1.1%) but exceeds that
for women 40–44 years old (0.6%). The proportions of life-years lost to breast cancer are
also similar for women 45–49 years old and
50–54 years old at diagnosis, with both approximately 15% of total life-years lost. Because of these similarities, the ACS supported similar screening regimens for women in
these age groups. The ACS discounted the
percentage of years of life lost for women
40–44 years old, which was almost as high,
instead emphasizing the lower breast cancer incidence for those women. The ACS
suggested that some women 40–44 years
old, albeit a minority, might reasonably decide to forego screening mammography after
weighing benefits and risks.
American College of Radiology
Guidelines
The American College of Radiology
(ACR) recommends annual screening mammography for women of average risk beginning at 40 years old [37]. In formulating
their guidelines, the ACR considered evidence from the RCTs, observational studies, U.S. screening data, modeling studies,
and other peer-reviewed literature. The regimen advocated by the ACR maximizes lives
saved and years of life gained. In contrast to
the USPSTF and ACS, the ACR considers
the substantial number of life-years lost to
breast cancer to be paramount and fully recommends annual screening of women 40–49
years old. The ACR also recognizes additional benefits of screening not taken into account by the USPSTF and ACS, including decreased need for extensive surgery and toxic
systemic therapies and lower recurrence risks
when breast cancer diagnosis occurs at earlier stages [38]. In addition, screening provides
opportunities for breast cancer risk reduction
through identification of high-risk lesions, almost all of which are nonpalpable. The ACR
agrees that women should be informed of the
risks of screening, emphasizing that the most
common risk is recall for additional mammography or ultrasound. The ACR notes that
86% of women view recall as an acceptable
trade-off for earlier breast cancer diagnosis
[39]. They note that in the United States, biopsy (generally percutaneous) occurs after
less than 2% of screening examinations and
cites modeling data that indicate, on average,
1 year of life gained for every benign biopsy
[40]. Finally, the ACR concluded that the benefits of screening greatly outweigh the risk of
overdiagnosis, which is likely less than 10%
and is unaffected by either earlier initiation
of or more frequent screening.
Cancer Intervention and Surveillance
Modeling Network Modeling Studies
Modeling studies facilitate comparison
of different screening regimens. Modeling
can incorporate the performance of modern
technology and better reflect current practice in the United States than RCTs conducted decades ago using outdated techniques.
Models also can account for longer durations
of screening exposure than RCTs and can include lifetime follow-up. The improvement
in case-fatality rate potentiated by earlier
screening becomes apparent only with sufficiently long duration of screening and with
sufficient delay after onset of screening [41].
The USPSTF relied on models developed by Cancer Intervention and Surveillance Modeling Network (CISNET), a National Cancer Institute–funded consortium
of investigators who perform statistical
modeling of cancer prevention, screening,
and treatment [42, 43]. CISNET investigators used models created by six independent modeling teams to compare 20 different screening strategies that varied by age of
initiation and cessation of screening as well
as screening intervals. Benefits modeled included reduction in breast cancer–specific
mortality and life-years gained. Risks included false-positive interpretations, benign
biopsies, and overdiagnosis. Differences existed among individual models; for example,
not all models included DCIS or were calibrated for breast cancer incidence. For the
2016 USPSTF recommendations, CISNET
models were updated to include digital
mammography data from the BCSC. Models assumed 100% adherence to screening,
prompt follow-up of abnormal results, and
optimal treatment. More recent models estimated greater reductions in breast cancer–
specific mortality attributed to increased
sensitivity of digital compared with filmscreen mammography, along with improvements in therapy and changes in underlying
breast cancer trends [33, 34].
Results of Modeling Studies
Number Needed to Screen Versus Number
Needed to Invite
A major criticism of the 2009 USPSTF
guidelines was their use of NNI as a measure of screening effectiveness. Although
NNI may be appropriate for RCTs, the
number needed to screen (NNS) reported
in population studies is a more clinically
relevant metric [44–47]. Because of noncompliance and contamination in RCTs,
NNI is approximately 25–30% greater than
NNS, which is based on women actually
screened. On the basis of averaged results
of the six CISNET models used for 2009
USPSTF guidelines, the NNS to save one
life with annual screening mammography
in women 40–49 years old is 746, which is
substantially lower than the USPSTF’s NNI
estimate of 1904 women but which they
deemed too high to justify screening [45].
Updated models that incorporate digital
mammography data reduce the NNS in this
age group to 588, reflecting the improved
performance of digital mammography in
younger women [44].
AJR:210, February 20183
Number Needed to Screen per Life-Year Gained
For younger women, an even better measure of screening benefit is NNS per life-year
gained. When death from breast cancer is
averted through screening, a younger woman gains more life-years than an older woman because the former has a longer life expectancy. Updated CISNET models indicate
that only 20 40- to 49-year-old women need
to undergo annual screening to save 1 year
of life, compared with 45 70- to 74-year-old
women undergoing biennial screening [44,
45]. By focusing on mortality reduction and
not life-years gained, the USPSTF justified
screening women who are 70–74 years old
but not those 40–49 years old. Years of life
gained, however, constitute an equally important measure of screening benefit.
Model Estimates of Benefit When Screening
Starts at 40 Years Old
Considering screening mammography over
a lifetime, CISNET models indicate that the
added benefit of screening women 40–49
years old is substantial and that the benefit is
greater with annual than with biennial screening (Fig. 1). Specifically, adding annual digital
mammography screening of women 40–49
years old to a regimen of biennial film-screen
screening of women 50–74 years old yields
27% more lives saved and 47% more lifeyears gained [48]. Annual rather than biennial digital mammography screening of women ages 40–49 yields 42% more lives saved
and life-years gained [44]. This is because
screening annually detects cancers when they
are less advanced than at biennial screening,
resulting in fewer breast cancer deaths after
treatment with modern therapies [49].
Another study incorporating digital mammography data compared no screening to 11
different digital mammography screening
strategies using a CISNET model adapted
to Canada [50]. Investigators found that annual screening for women 40–49 years old
yielded 54 life-years gained per 1000 women. Considering life-years gained, a greater
impact was achieved by screening women in
this age group than by reducing the screening interval from biennial to annual in older
women. Although annual rather than biennial screening was associated with more falsepositives, it reduced the NNS per life saved
and per life-year gained [50].
The validity of these CISNET estimates
of screening benefit is strengthened by other
types of modeling studies yielding strikingly similar results. For example, using the re-
4
Fig. 1—Percentage
mortality reduction
from various screening
strategies. Annual
screening (A) for
women 40–84 years
old (A40–84, solid
arrow) is estimated
to have 71% greater
mortality benefit than
biennial (B) screening
for women 50–74 years
old (B50–74, dashed
arrow). Data are means
(diamonds) and ranges
(dashed vertical lines) of
six models presented in
Mandelblatt et al. [33].
55
Mean and Range of 6 Models
50
45
A40–84
40
Mortality Reduction (%)
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Ray et al.
35
B40–84
30
25
B50–74
20
B55–69
15
B50–84
B50–79
B50–69
B60-69
10
5
0
0
10,000
20,000
30,000
40,000
No. of Mammograms per 1000 Women Screened
ported 24% mortality reduction shown with
biennial screening of women 40–49 years
old in the Swedish Two-County Trial [51], it
was estimated that mortality could be reduced
by 35% with annual screening, using modeling based on the size and stage of interval
and screen-detected cancers [47]. Similarly, a
Markov chain model estimated improvement
in mortality reduction from 18% to 36%, with
a change from biennial screening to annual
screening for women 40–49 years old [52].
Weighing Benefits and Risks
Analysis of CISNET data reveals that an
individual woman is likely to experience
the risks of screening infrequently. According to the 2009 CISNET models used by the
USPSTF, the risks for women 40–49 years old
undergoing annual screening, on average, consist of recall for diagnostic workup once every
13 years, a negative biopsy every 187 years,
a missed breast cancer every 1000 years, and
a fatal radiation-induced breast cancer every
76,000–97,000 years [40, 46]. More than 80%
of all recalls do not result in biopsy but merely
involve additional mammographic views, ultrasound, or both [53, 54]. Most women report
that the anxiety associated with recall and bi-
opsy is minor and transient [55]. Furthermore,
according to recent analysis of CISNET data,
the ratio of life-years gained to false-positive
biopsies is 1.0 for women undergoing annual screening between the ages of 40 and 84
years old [40]. This ratio can be expressed as
accepting the possibility of a benign biopsy
in exchange for the possibility of extending
one’s life by 1 year.
Data provided to the USPSTF by the
BCSC indicate that the numbers of women
recalled from screening to find one cancer at
40–49 years old, 50–59 years old, and 60–69
years old are 47, 22, and 14, respectively [32].
A higher proportion of women 40–49 years
old undergo initial screening examinations,
however, and it is well documented that initial (prevalent) screening examinations are
associated with higher recall rates than subsequent incidence examinations because of
the lack of prior examinations that can be
used for comparison [56, 57]. Therefore, delaying screening until after a woman is 50
years old would merely transfer rather than
eliminate the higher recall rate of baseline
screening to the older age group, as acknowledged in Table 5 of the 2016 USPSTF guidelines, which reports identical rates of false-
AJR:210, February 2018
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Screening Mammography in Women 40–49 Years Old
positive recalls for women starting screening
at the ages of 40 and 50 years old [31].
Overdiagnosis (identification of cancers
that would not adversely affect patients over
their lifetimes) was emphasized as an important risk of screening by the USPSTF in their
2016 guidelines. However, they acknowledged the uncertainty of overdiagnosis estimates, which vary widely in the literature.
The most reliable estimates, which are either
based on RCT data with long-term followup or observational data that are adjusted for
temporal trends in breast cancer incidence,
risk factors, and lead time, have estimated overdiagnosis to be 10% or less [58–61].
Moreover, overdiagnosis is more likely to
affect older rather than younger women because of differences in life expectancy. Finally, neither earlier initiation of screening
nor annual versus biennial screening will
increase the frequency of overdiagnosis because cancer would simply be detected on
the next routine screening examination [62].
Therefore, overdiagnosis should not factor
into decisions regarding the appropriate age
to begin screening or screening interval.
Screening Intervals
For screening to be effective, the screening interval needs to be shorter than the
lead time for cancer detection. Moskowitz
[63] calculated the lead time in the Cincinnati Breast Cancer Detection Demonstration
Project by determining how long it took for
the cancer detection rate to return to baseline
after screening was discontinued. For women
35–49 years old, the mean lead time was 1–2
years, whereas it was 3.5–4 years for women
50 years old and older. In the Swedish TwoCounty trial, Tabar et al. [51] estimated the
lead time to be 1.7 years for women 40–49
years old and 2.6–3.8 years for women 50–74
years old [51]. Thus, given a lead time of 1–2
years for women in the former age group, annual screening mammography is necessary
to intercept more rapidly progressive cancers
and reduce breast cancer deaths.
For their 2015 guidelines, the ACS reviewed the evidence regarding screening
intervals. They cited a meta-analysis of the
RCTs showing that among women randomized before the age of 50 years old, only
those screened at intervals less than 24
months had a significant reduction in breast
cancer mortality [64]. The ACS also commissioned an analysis by the BCSC that
showed that premenopausal women screened
every 23–26 months were more likely to be
diagnosed with larger tumors and more advanced-stage disease than women screened
every 11–14 months [27]. Lastly, the ACS cited the 2009 CISNET models, all of which
showed that annual screening yielded greater mortality benefit than biennial screening
for all age groups [33]. Therefore, the ACS
strongly recommended annual screening intervals for women 45–54 years old undergoing screening mammography and gave a
qualified recommendation for the same interval for women 40–44 years old. The ACR
recommendation for annual screening beginning at the age of 40 years old maximizes
mortality benefit. The USPSTF chose to recommend biennial screening because of the
absence of RCTs that directly compared annual versus biennial screening and because it
minimized reliance on observational studies.
Risk-Based Screening
Selective screening of women 40–49 years
old who are at elevated risk of developing
breast cancer has been proposed as a means
of improving the benefit-to-risk ratio. In their
2009 guidelines, the USPSTF recommended screening women 40–49 years old if they
were at high risk of breast cancer [31]. In their
2016 guideline update, the USPSTF supported screening women in the same age group
who had a history of breast cancer in a firstdegree relative because they have the same
relative risk as women 50–59 years old who
do not have a family history of breast cancer
[36]. Van Ravesteyn et al. [65] proposed that
women 40–49 years old should be screened
biennially if they have a threefold increased
risk and annually only if they have fourfold
increased risk, suggesting it would achieve
the same benefit-to-risk ratio as biennial
screening of women 50–74 years old [65].
The adverse consequences of risk-based
screening become evident when considering
that 80% of women with newly diagnosed
breast cancers have no known major risk factors [66, 67]. Multiple retrospective studies
have shown that 60–80% of women 40–49
years old with breast cancer had no family
history of the disease, and 80–90% did not
have a first-degree relative with breast cancer
[30, 68–70]. Therefore, a risk-based screening approach would deny the life-extending
benefits of screening to approximately 80%
of women 40–49 years old.
In a meta-analysis, Nelson et al. [71] found
that the only risk factors to confer a twofold
higher relative risk among women 40–49
years old are a first-degree family history or
extremely dense breasts. According to a recent retrospective study from the University of California San Francisco spanning the
years 1997–2012, 88% and 86% of women
with screen-detected breast cancer did not
have very strong family history of breast cancer or extremely dense breast tissue, respectively [72]. Among patients with screen-detected malignancies, 76% had neither a very
strong family history nor extremely dense
breasts [72]. These data underscore the fact
that limiting screening to only those women
40–49 years old who are considered to have
elevated risk would miss the great majority
of detectable breast cancers.
Conclusion
The burden of breast cancer among women 40–49 years old is substantial, particularly when life-years lost without screening
are taken into account. A large body of evidence shows that annual screening mammography beginning at 40 years old results
in the greatest mortality benefit and the most
life-years gained. Efforts to limit screening
to women 40–49 years old who have elevated
risk would miss the great majority of detectable breast cancers. As screening technology
continues to improve, the balance of benefits
versus risks is expected to further shift in favor of screening women 40–49 years old.
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