Screening For Breast Cancer

Screening for Breast
Cancer
a, b
Bethany L. Niell, MD, PhD *, Phoebe E. Freer, MD , Robert Jared Weinfurtner,
a c a
MD , Elizabeth Kagan Arleo, MD , Jennifer S. Drukteinis, MD
KEYWORDS
Screening Mammography Ultrasound MR imaging Cancer detection rate
KEY POINTS
Early detection with screening mammography significantly reduces breast cancer deaths by 20%
to 40%.
Annual screening mammography of women aged 40 to 84 prevents more deaths from breast
cancer than biennial screening of women 50 to 74 years old.
Currently, it is recommended that supplemental screening with ultrasound or MR imaging be
performed in addition to mammography.
The American Cancer Society recommends annual screening mammography and supplemental
screening MR imaging for women with an estimated lifetime risk of breast cancer 20%, BRCA
mutation carriers, first-degree relatives of BRCA mutation carriers who remain untested, women
with a history of mediastinal irradiation between the ages of 10 and 30, and women with certain
genetic syndromes.
INTRODUCTION reader will be better equipped to have informed

discussions with patients and medical profes-
In the United States in 2017, an estimated 255,180 sionals regarding the benefits and disadvantages
1
new breast cancer cases will be diagnosed. In of breast cancer screening.
2013, breast cancer deaths totaled 773,100 person-
years of life lost, with each death aver-aging 19 SCREENING MAMMOGRAPHY
2
years of life lost. The goal of screening is to find
cancers when still curable (ie, smaller and node- Early detection of breast cancer with screening
negative) to decrease breast cancer– specific mammography significantly reduces the risk of death
3,4
mortality. Since screening mammography became from the disease. The strongest evidence is
widespread in the United States during the 1980s, provided by randomized controlled trials (RCTs), and
age-adjusted breast cancer mortality in women has pooled estimates show that screening
steadily decreased (Fig. 1). This article aims to mammography can reduce breast cancer mortal-ity
5
review the most commonly used breast imaging by at least 20%. Eight RCTs have been per-formed
modalities for screening, discuss how often and and published. The first was initiated in 1963, the
when to begin screening with spe-cific imaging 6
Health Insurance Plan (HIP) trial. It recruited 62,000
modalities, and examine the pros and cons of women ages 40 to 64 from the HIP of greater New
screening. By the end of this article, the York and half were invited to
Disclosure Statement: The authors have nothing to disclose.

radiologic.theclinics.com
a Division of Breast Imaging, Department of Diagnostic Imaging, H. Lee Moffitt Cancer Center and Research
b
Institute, 12902 USF Magnolia Drive, Tampa, FL 33612-9416, USA; Division of Breast Imaging, Department of
Radiology, University of Utah Hospitals, Huntsman Cancer Institute, 2000 Circle of Hope Drive, Salt Lake City, UT
c
84112, USA; Division of Breast Imaging, Department of Radiology, Weill Cornell Medical College, Weill Cornell
Medicine, 425 East 61st Street, New York, NY 10065, USA
* Corresponding author.
E-mail address: bethany.niell@moffitt.org
Radiol Clin N Am 55 (2017) 1145–1162

http://dx.doi.org/10.1016/j.rcl.2017.06.004
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1146 Niell et al
35
30
per 100,000 women
25
20
15
rate
10
Death
0
19 7519 7619 7719 7819 7919 8019 8119 8219 8319 8419 8519 8619 8719 8819 8919 9019 9119 9219 9319 9419 9519 9619 9719 9819 9920 0020 0120 0220 0320 0420 0520 0620 0720 0820 0920 1020 1120 1220 13
Fig. 1. Age-adjusted breast cancer death rate in American women decreased after the widespread introduction of
screening mammography in the 1980s. (Data from the Surveillance, epidemiology, and end results [SEER] pro-gram
from 1975–2013 and US Mortality Files, National Center for Health Statistics, Centers for Disease Control and
Prevention. Rates are per 100,000 and are age-adjusted to the 2000 US population (19 age groups - Census P25-
1130).)
undergo annual clinical breast examination and at 18-month to 24-month intervals resulted in a
screening mammography. Breast cancer mortality 22% reduction in breast cancer mortality.11
was reduced by 22% among those invited to The Edinburgh trial evaluated the efficacy of
screen (Table 1).3,7,8 mammography and CBE in 3 cohorts of women
recruited between 1978 and 1985. Patients were ran-
domized by clinical practice to biennial single-view
Pooled estimates from RCTs demonstrate that mammography (initial screening round was 2-view) plus
screening mammography can reduce breast 12
annual CBE versus CBE alone. With 14 years of
cancer mortality by at least 20%.
follow-up from 28,628 women offered screening and
26,026 controls, invitation to screening decreased
13
In the late 1970s, 2 trials in Sweden, the Swedish breast cancer mortality by 21% to 29%. The
Two-County trial and Malmo¨ investigated the effect Stockholm trial included 40,000 women invited to
of screening mammography without phys-ical biennial screening and 20,000 women as controls.
14
examination. The Swedish Two-County trial The Swedish Two-County trial was already showing
consisted of 133,065 women ages 40 to 74, who significant benefit; the Stockholm trial was terminated
were randomized into a group invited to single-view after only 2 rounds of screening with single-view
screening mammography and a control group. mammography and showed no sta-tistically significant
Screening intervals were 24 months for ages 40 to mortality reduction (see Table 1).
9
49, and 33 months for those 50 to 74. After 3 The Canadian National Breast Screening Trials
decades of follow-up, invitation to screening resulted in women ages 40 to 49 (CNBSS-1) and 50 to 59
in a 27% to 31% reduction in breast cancer mortality, (CNBSS-2) investigated the efficacy of CBE and
with only 45% of pre-vented breast cancer deaths screening mammography on breast cancer mor-
occurring in the first 10 years. At 10 years of follow- tality reduction.15,16 Women were asked to volun-
up, 1303 women were needed to screen for 7 years teer to participate, and following CBE,
to save 1 life. At 20 years, 577 women were needed approximately 50,000 volunteers were included in
to screen, and at 29 years, 519 women were needed CNBSS-1 and 40,000 in CNBSS-2.15,16 At 7
10
to screen to save 1 life. The observed number of years of follow-up in CNBSS-1, women invited to
prevented breast cancer deaths increases with screening had 36% greater mortality from breast
follow-up duration, providing evidence that esti- cancer than control women. At 25 years of follow-
mates of absolute benefit and number needed to up, breast cancer mortality was identical in the
screen requires trial follow-up intervals exceeding 20 mammography and control arms.17 Flawed study
years. Malmo¨ recruited approximately 31,000 to design and suboptimal image quality and
each group, women ages 45 to 70 (MMST1) and interpretation may explain why the Canadian Na-
ages 43 to 49 (MMST2). Invitation to screening tional Breast Screening Trials are outliers
compared with other RCTs (see Table 1). In the
Screening for Breast Cancer
Table 1 The most recent RCT in mammography started

Evidence for mortality reduction from in 1982 in Gothenburg, Sweden. Approximately
screening mammography 52,000 women aged 39 to 59 years were
random-ized, and the screening arm offered 2-
Mortality view mammography every 18 months.20 After 14
Reduction years of follow-up, women ages 39 to 59 invited
95% to screening had a 23% mortality reduction.21
Confidence RCTs provide the strongest evidence for mortality
Trial or Data % Interval reduction; however, RCTs underestimate the
3,8
expected benefit because some women invited to
HIP RCT 22 0–39 screening do not actually undergo screening
11
Malmo RCT 22 5–35 (noncompliance) and some women in the control
10 group go outside the study to obtain a screening
Swedish Two-County RCT 27 11–41
Edinburgh RCT
13
21 2–40 mammogram (contamination). Service screening
3,11 studies use large, population-based screening
Stockholm RCT 10 28–37
17
programs and measure outcomes from women who
NBSS1 and NBSS2 RCTs 1 12–12 actually undergo screening. Euro-pean service
21
Gothenburg RCT 23 0–40 screening data demonstrate a 38% reduction in
3 breast cancer mortality among women who
Overall RCTs 20 14–27
European service screening 25 24–31 underwent screening, compared with a 25%
22 22
Invited vs not invited reduction among women invited to screen.
European service screening 38 31–44 Canadian service screening data demonstrate a
Screened vs not screened
22 40% reduction in mortality and a 44% mortality
reduction in women ages 40 to 49 who underwent
Canadian service 40 33–48
23 23
screening screening. Case control studies compare how
European case control 48 35–58 often and when screening was done in 2 groups of
studies women, those who died from breast cancer (cases),
22 and those who are alive (matched controls). A meta-
Screened vs not screened
analysis of European case control studies demon-
Abbreviations: HIP, Health Insurance Plan; NBSS, National strated a 48% decrease in breast cancer mortality in
Breast Screening Trial; RCT, randomized controlled trial. women screened, and a case control study in
22,24
Western Australia showed a 52% reduction.
first round of screening, significantly more women
with palpable and advanced (lymph node–posi-tive)
breast cancer were randomized to the screening RCTs underestimate the potential benefit of
arm. For women with 4 or more positive nodes, the screening mammography because some women
ratio between those assigned to the screening group invited to screening do not actually un-dergo
compared with the control group was 19:5, and 17 of screening (noncompliance) and some women in
the 19 had palpable cancers despite the trials’ the control group go outside the study to obtain a
intention to evaluate screening mammography. screening mammogram (contamination).
18
These data suggest flawed randomization. Among
women in the CNBSS-1 control group diagnosed
with breast cancer, the greater than 90% 5-year
survival is higher than the less than 80% survival
reported in the United States and Canada during a Service screening studies measure outcomes
similar time period, which may be in part due to the from women who actually undergo screening in
flawed randomiza-tion process and the recruitment large, population-based screening programs.
18 Among women who underwent screening in
of volunteers. Due in part to the high survival in the Europe and Canada, breast cancer mortality was
control arm, the CNBSS trials lacked statistical decreased by 38% and 40%, respectively.
power to demonstrate a 40% breast cancer mortality
reduc-tion, let alone a more reasonable 20% to 30%
18
reduction as expected from other RCT trial data.
An external review judged more than 50% of the PERFORMANCE BENCHMARKS
mammograms as poor or unaccept-able, and the FOR SCREENING MAMMOGRAPHY
CNBSS’s own radiologist revealed that 42% of
Screening mammography detects 2 to 8 cancers
missed cancers were visible on a previous
18,19 per 1000 mammograms.25–27 The sensitivity of
mammogram. mammography decreases in women with dense
1148 Niell et al
breasts, measuring 30% to 64% for extremely dense images following intravenous iodine-based contrast
breasts compared with 76% to 98% for fatty media injection. A recent meta-analysis of CESM
28–33 demonstrated very high sensitivity (98%) but limited
breasts. Decreased sensitivity in denser breasts
39
is attributable to the concept of masking. Cancers specificity (58%). At this time, CESM and CE-DBT
have similar x-ray attenuation as dense remain active areas of research and are not
fibroglandular tissue, resulting in obscuration of the currently recommended for screening.
31
tumor. With this limitation, supplemental screening
modalities have been investigated.
SCREENING ULTRASOUND
DIGITAL BREAST TOMOSYNTHESIS Ultrasound has shown utility in detecting breast can-
cer as a supplemental screening modality since the
Digital breast tomosynthesis (DBT) is a digital 1980s.
40,41
Compared with screening mammog-
mammogram technique in which tomosynthesis raphy alone, screening ultrasound in combination
images are constructed from a series of low-dose with mammography can increase cancer detection
images acquired as the x-ray source moves over the (additional cancer detection rate [ACDR]) but at the
breast, which reduces the impact of overlapping cost of increased callbacks (“recall rate”) and a large
breast tissue. Eliminating tissue overlap increases number of biopsies needed to identify 1 breast can-
conspicuity of lesions while reducing false positives cer (positive predictive value 3 [PPV 3] 5 number of
due to tissue summation. DBT detects malignancies 42–
34 cancers detected/number of biopsies per-formed).
occult on digital mammography (Fig. 2). Two ma- 45
In patients at increased risk of devel-oping breast
jor prospective clinical trials have been performed
cancer, supplemental screening ultrasound can
comparing full-field digital mammography (FFDM) to
detect an additional 4.2 cancers per 1000 women
FFDM with DBT. In 12,621 screening examina-tions
in the Oslo Tomosynthesis Screening Trial, with 11 cancers per 100 biopsies performed (PPV 3 5
tomosynthesis with FFDM increased the invasive 11%), compared with a PPV 3 of 29% for
cancer detection rate by 40% and decreased false mammography alone in the first year of screening
35 42,43
positives by 15%, compared with FFDM alone. In ultrasound. PPV3 may increase in subsequent
7292 Italian women enrolled in the Screening with screening rounds (as high as 16%) while maintaining
Tomosynthesis or Mammography (STORM) trial, an ACDR of 2.3 to 3.7 per 1000 in subse-quent
43,46
DBT increased the cancer detection rate from 5.3 to years. As expected, screening ultrasound in
8.1 per 1000 examinations with a simulta-neous women with breast density as their only risk factor
17% reduction in recall rate.
36
Retrospective detects fewer cancers and requires more biopsies
per cancer detected, with ACDR of 3.2 per 1000 in
analysis of 173,663 FFDM-DBT and 281,187 FFDM 44,45
examinations from 13 sites in the United States the first year and PPV3 of 6.5% to 6.7%. In a
demonstrated a 29% increase in cancer detection recent meta-analysis, supplemental screening ultra-
rate with a concomitant 15% decrease in recall rate sound demonstrated a PPV3 of 2% to 8% and ACDR
37 47
compared with FFDM alone. of 4.4 per 1000 with a recall rate of 14%. Because
ultrasound detects masked breast cancers obscured
by breast parenchyma on mammography, screening
DBT increases cancer detection and decreases ultrasound halves the rate of interval can-cers
recall rate, compared with digital mammog- (cancers that present within 1 year of a negative
raphy. 48
screening mammogram). In women with dense
breasts and a negative screening mammogram,
A synthesized mammogram can be created by supplemental screening with ultrasound had an
summing and filtering a stack of reconstructed DBT ACDR of 7.1 per 1000 compared with 4 per 1000 for
images, resulting in an FFDM equivalent image and 49
DBT with similar recall rates.
an examination with roughly half the dose of a
38
standard combined FFDM and DBT examination.
Screening ultrasound detects 2 to 4 additional
cancers per 1000 examinations but requires
many recalls and a large number of biopsies
CONTRAST-ENHANCED MAMMOGRAPHY needed to identify each breast cancer.
AND DIGITAL BREAST TOMOSYNTHESIS
Neovascularity causes tumors to enhance, usually

more so than the surrounding normal parenchyma, In addition to the drawbacks of increased re-
following administration of intravenous contrast calls and lower PPV, another disadvantage to
agents. Contrast-enhanced spectral mammog-raphy whole breast ultrasound is acquisition time and
(CESM) or DBT acquires FFDM or DBT interpretation time. Screening ultrasound trials
report a 10-minute to 20-minute acquisition time SCREENING BREAST MR IMAGING

and 7-minute to 10-minute interpretation
Breast MR imaging with gadolinium is highly sen-
time.42,50,51 Screening ultrasound with automated
sitive ( 90%) for the detection of breast can-
whole breast units yields similar results to
screening with hand-held whole breast ultrasound cer.52–54 Although initial reports suggested lower
performed by a radiologist or a breast sensitivity for the detection of ductal carcinoma in
situ (DCIS), advances in image quality and
technologist.47
Fig. 2. Increased lesion conspicuity

on DBT images increases cancer
detection rate on DBT compared with
FFDM. (A) CC and (B) MLO FFDM
images show scattered fibro-
glandular densities in the right breast
without definite abnormal-ity.
Selected CC (C) and MLO (D) to-
mosynthesis slices demonstrate
architectural distortion in the right
upper central breast. Targeted ultra-
sound demonstrated no sono-graphic
correlate. Pathology from
tomosynthesis-guided percutaneous
biopsy yielded invasive ductal carci-
noma. CC, craniocaudal; MLO, me-
diolateral oblique.
1150 Niell et al
image interpretation have resulted in 98% and 85% In addition to its utility in asymptomatic women,
sensitivities for high-grade and non–high-grade breast MR imaging detects contralateral cancers
55 in 3.1% of women with newly diagnosed breast
DCIS, respectively. In prospective trials of
asymptomatic high-risk women, screening MR cancer and a negative contralateral
imaging was more sensitive (90%–93%) than clin- mammogram.57
ical breast examination (18%), mammography High-risk women undergoing annual screening
(33%–50%), ultrasonography (37%–52%), or mammography and supplemental screening MR
mammography combined with ultrasonography imaging do not benefit from the addition of screening
52,54,56 52,54,56
(48%–63%). Up to 31% to 52% of MR im- ultrasound. However, women un-dergoing
aging–detected breast cancers were detected only annual screening mammography and supplemental
52,54,56
on MR imaging (Fig. 3). screening ultrasound do benefit from the addition of
The cancer yield of MR imaging is approximately 14 MR imaging. In women with dense breasts and
43,52,53 elevated breast cancer risk
to 30 per 1000 high-risk women screened.
Fig. 3. Screening breast MR imaging detects malignancies occult on other imaging modalities. (A) CC and (B) MLO
FFDM images of the left breast demonstrate no suspicious findings. (C) Early postcontrast T1-weighted fat sub-
tracted axial and (D) maximum intensity projection images from screening breast MR imaging demonstrate a 7-
mm enhancing mass with spiculated margins in the left breast at 12 o’clock 10 cm from the nipple. Pathology from an
MR imaging–guided percutaneous breast biopsy yielded invasive ductal carcinoma (grade 1).
efforts will investigate noncontrast screening breast MR
imaging using diffusion-weighted imaging.
who underwent 3 rounds of annual screening ultra-

sound and mammography, cancer detection rate
increased from 11.4 per 1000 for mammography
plus ultrasound to 26.1 per 1000 with the addition of
a single MR imaging screen (ACDR of 14.7/1000 for
43
MR imaging). MR imaging–detected breast
cancers often exhibit underlying pathologic markers
of biologic aggressiveness; for example, MR imaging
better detects intermediate and high-grade DCIS in
addition to small and node-negative invasive tumors,
suggesting that MR im-aging–detected cancers are
52,53
less likely to contribute to overdiagnosis.
Screening MR imaging also results in a near zero
52
rate of interval cancers. Despite the benefits of
screening MR imaging, fewer than half of
documented BRCA mutation carriers and fewer than
one-third of women with a 20% lifetime risk have
58
received screening breast MR imaging.
Screening breast MR imaging demonstrates high

sensitivity for the detection of breast can-cer. Up
to one-half of MR imaging–detected breast
cancers are seen only on MR imaging.
Disadvantages of breast MR imaging include the

need for intravenous gadolinium contrast
administration, the lack of data regarding decreased
breast cancer–specific mortality, expense and lack
of availability, as well as decreased specificity. In
published studies to date, the specificity of MR
imaging with mammog-raphy was lower than
mammography alone (range 73%–97% vs 91%–
59
100%). However, recent data suggest that the
specificity of MR imaging when added to
mammography approaches 96.0% to 97.6%,
compared with 99.0% for
mammography alone, for experienced
readers.52,54 With regard to expense, supple-
mental screening MR imaging in patients with
elevated breast cancer risk was 2.5 times more
expensive per life-year gained with an estimated
mortality reduction of 25% compared with 17%
with mammography alone.60 To address the
expense and resource limitations, an abbreviated
screening breast MR imaging protocol can be ac-
quired in 3 minutes, requires an average of 28
sec-onds to read, and demonstrates equivalent
diagnostic accuracy to the 17-minute acquisition
complete protocol.61 A prospective, multicenter
trial of abbreviated screening breast MR imaging
is currently planned. Ongoing and future research
The US Preventive Services Task Force (USPSTF),
Screening for Breast Cancer the American Cancer Society (ACS), and the
American College of Radiology (ACR) are the 3
main organizations that have issued evidence-based
ADDITIONAL BREAST IMAGING MODALITIES guidelines for breast cancer screening in the
average-risk woman based on estimates of risk
Positron emission mammography (PEM) 5,76,77
remains investigational but uses mild versus benefits (Table 2). All 3 organiza-tions
compression with ac-quisitions in 2 views, agree that screening mammography saves lives,
similar to mammography. Data from and, at a minimum, should be performed in women
experienced readers suggest sensitivity of 50 to 74. All 3 guidelines recognize that annual
90% to 96%, although PEM may not reliably mammography should remain an option for each
detect lower-grade malignancies and has a woman starting at the age of 40 because all 3
higher radiation dose than mammography, organizations acknowledge that annual screening
62–67 mammography beginning at age 40 saves the most
limiting its screening utility. Breast-
specific gamma im-aging (BSGI) uses a lives from breast cancer.
99m
radiotracer, most commonly Tc-sestamibi,
which accumulates in tumor more than
normal breast tissue. To date, no large The USPSTF, ACS, and ACR are the 3 main
prospective studies have been performed, orga-nizations that have issued evidence-based
and BSGI is not currently recommended for guidelines for breast cancer screening in
screening. BSGI demonstrates sensitivity average-risk women. All 3 guidelines state that
greater than 90% and specificity of 60% to annual mammography should remain an option
68–72 for women starting at age 40 because annual
80%, but the exam-ination is limited by
screening mammography beginning at age 40
long examination time and high radiation
68,73
saves the most lives from breast cancer.
dose.
Breast thermography cannot and should

not be used to diagnose breast cancer due The ACR and Society of Breast Imaging recom-
to unaccept-ably low sensitivity (61%) and mend that women at average risk of breast cancer
begin annual screening mammography at age 40
specificity (74%).74,75
and stop screening when life expectancy is less than
5 to 7 years on the basis of age or comorbid
BREAST CANCER SCREENING GUIDELINES
1152 Niell et al
Table 2
Screening mammography guidelines for average-risk women
Age to Start How Often Age to Stop Comment

American College of 401 Annual Continue as long as
Radiology in good health
American Cancer 45–54 Annual Until approximately Option to start
Society 551 Biennial 10 y of life left screening 40–44; if
start at 40,
recommend
annual screening
40–54
US Preventive 50–74 (Category B Biennial 75 Individual decision to
Services Task Force recommendation) start screening at
ages 40–49
(Category C)
conditions and/or when abnormal results of regular screening mammography starting at age 45
screening would not be acted on due to similar years (strong recommendation). Women aged 45 to
reasons.78 54 years should be screened annually (qual-ified
The USPSTF recommendation (2009 and 2016) is recommendation). Women 55 years and older
biennial screening mammography for women aged should transition to biennial screening or have the
50 to 74 years (B recommendation). The de-cision to opportunity to continue screening annually (quali-fied
start screening mammography in women before age recommendation). Women should have the
50 years should be an individual one. Women who opportunity to begin annual screening between the
place a higher value on the potential benefit than the ages of 40 and 44 years (qualified recommen-
potential harms may choose to begin biennial dation). Women should continue screening
screening between the ages of 40 and 49 years (C mammography as long as their overall health is
recommendation). The USPSTF concludes that the good and they have a life expectancy of 10 years or
current evidence is insufficient to assess the balance 5
longer (qualified recommendation). The ACS
of benefits and harms of screening mammography in defines a strong recommendation as one for which
77
women aged 75 years or older (I statement). The “most individuals in this situation would want the
Task Force defines a B recommendation as one in recommended course of action, and only a small
which “there is high certainty that the net benefit is proportion would not” and a qualified recommen-
moderate or there is moderate certainty that the net dation as one for which “the majority of individuals in
benefit is moder-ate to substantial.”
77
Under the this situation would want the suggested course of
5
Patient Protection and Affordable Care Act, “insurers action, but many would not.”
now must cover evidence-based services for adults The National Comprehensive Cancer Network
that have a rat-ing of ‘A’ or ‘B’ in the current (NCCN) and the American Congress of Obstetri-
USPSTF.”
79
Based on the USPSTF cians and Gynecologists (ACOG) agree with the
ACR, recommending mammography screening
recommendations, private in-surers will cover
starting at age 40 and continuing annually, regard-
biennial screening mammog-raphy beginning at age 81,82
40; however, women ages 40 to 49 or older than 75 less of risk. The American College of Surgeons
who choose routine screening, as well as women of Oncology Group recommends following the ACS
any age who want to be screened annually may not guidelines. The American Academy of Family Phy-
be guaranteed coverage. As a result, Congress sicians and American College of Physicians both
83,84
recently enacted the Consolidated Appropriations recommend following the USPSTF guidelines.
Act, which included language from the Protecting
Access to Lifesaving Screenings Act (PALS) WOMEN WITH DENSE BREASTS
(H.R.3339) to delay implementation of the USPSTF
recommen-dations for 2 years and thus allow Approximately 40% to 50% of women undergoing
women continued access to screening screening mammography have dense breasts
80 (higher ratio of fibroglandular and stromal ele-
mammography in the interim.
ments relative to fatty tissue).85 The definition of
The ACS recommends that women with an “dense” is subjective by the radiologist and
average risk of breast cancer should undergo demonstrates moderate variability between
radiologists with 17% of patients being recatego- compared with mammography.89 Compared with
rized into dense versus nondense on subsequent mammography alone, supplemental ultrasound is
mammograms.86 Women with dense breasts predicted to prevent 0.36 additional cancer
have a 1.2-fold to 2.1-fold higher risk of breast deaths and lead to an additional 354 biopsies per
cancer compared with the average woman.87 1000 women screened biennially for 25 years. 90
Because dense tissue causes a “masking” phe- As such, screening ultrasound is unlikely to be
nomenon and obscures underlying cancers, considered cost-effective.90 The ACR recom-
women with dense breasts have more interval mends supplemental screening ultrasound in
cancers (a cancer diagnosed within 12 months of women with dense breasts and an elevated risk
a negative screening mammogram). The interval of breast cancer who cannot undergo MR
cancer rate is as much as 17-fold higher in imaging.91
women with extremely dense breasts compared
with women with the fattiest breasts.88
As of December 5, 2016, 28 states have enacted Clinicians may choose to offer supplemental
legislation that requires radiologists to notify pa- screening ultrasound, or other tests, to women
tients of their breast density. Although the wording of with dense breasts, given the increased cancer
the individual laws varies, most encourage a pa-tient detection. However, this remains controversial
due to the high frequencies of false-positive
to discuss with her referring provider whether she
recall and false-positive biopsy compared with
would benefit from supplemental screening tests.
mammography.
Individual clinical practices may choose to offer
supplemental screening ultrasound, or other tests, to
women with dense breasts, given the increased
cancer detection (Fig. 4). However, sup-plemental DBT may have its largest incremental cancer
screening for dense breasts remains controversial detection benefit over digital mammography in
due to the high frequencies of false-positive recall women with heterogeneously dense breasts and,
and false-positive biopsy when accessible, may thus be preferred over
Fig. 4. Supplemental screening DBT, ultrasound, and MR imaging incrementally increase cancer detection rate
(CDR) when added to digital mammography in women with dense breasts. PPV 3 is the positive predictive value of
biopsy and equals the number of cancers detected divided by the number of breast biopsies performed. (Data from
Tice JA, Ollendorf DA, Lee JM, et al. The comparative clinical effectiveness and value of supplemental screening
tests following negative mammography in women with dense breast tissue. Institute for Clinical and Economic
Review; 2013. Available at: https://icer-review.org/wp-content/uploads/2016/01/ctaf-final-report-dense-breast-
imaging-11.04.2013-b.pdf.)
1154 Niell et al
standard digital mammography.92 It should be imaging or supplemental screening in women

noted, however, that the benefit of DBT in with a <15% lifetime risk of breast cancer. NCCN
improving cancer detection does not persist in the guidelines state there is “insufficient evidence” to
fewer than 10% women who have extremely routinely recommend supplemental screening
dense breasts.92 tests such as ultrasound or MR imaging in
women who have dense breasts who are
“RISK-BASED” OR “PERSONALIZED” otherwise of low or average risk. 81 The USPSTF
OR “TAILORED” SCREENING states there is a dearth of evidence to
recommend supplemental screening tests in
In the emerging era of precision medicine, it is
women of average risk and dense breasts.47,77
un-likely that there will be a “one-size-fits-all”
approach to breast cancer screening. Women at
increased risk of breast cancer may benefit from SCREENING INTERMEDIATE-RISK WOMEN
supplemental screening with imaging examina-
Women with an intermediate risk of breast cancer
tions, such as DBT, MR imaging, or ultrasound.
(15% to <20% lifetime risk) include women with a
Supplemental screening should be in addition to,
prior personal history of breast cancer, lobular
and not as a replacement for, annual
neoplasia, and other atypias. Some consider
mammography.
women with dense breasts in the intermediate-
The 20% to 40% reduction in breast cancer risk category. For women with 15% to less than
mortality was observed in screening mammog- 20% lifetime risk, the 2007 ACS guidelines state
raphy RCTs and service screening studies in that there was insufficient evidence to recom-
women irrespective of risk. Existing data do not mend for or against supplemental breast MR im-
support the assertion that average-risk women do
aging.95 Subsequently published studies in
not benefit from screening. The idea that only
women with a personal history of breast cancer or
high-risk women should begin screening
a personal history of atypia on prior breast bi-
mammography at age 40 ignores the fact that
opsy suggest that these 2 groups of women
75% of women diagnosed with breast cancer at
demonstrate similar ACDR (w14–15 cancers per
ages 40 to 49 do not have a strong family history
1000 MR imaging examinations) on supplemental
or extremely dense breast tissue. 93 Ongoing screening breast MR imaging as high-risk
research studies, including the WISDOM trial, will women.96–104 The ACR appropriateness criteria
evaluate the effects of increased screening
ranks supplemental screening MR imaging in
including supplemental screening modalities in
intermediate-risk women as 7 and supplemental
high-risk women, while other studies are evalu-
ultrasound as 5 on a scale of 1 (not recommen-
ating decreasing mammography screening in low-
ded) to 9 (highly recommended).76
risk or average-risk women.94
SCREENING HIGH-RISK WOMEN

Average-risk women benefit from screening
mammography. Since 2007, the ACS has recommended annual
screening mammography and supplemental
screening MR imaging for women with an esti-mated
lifetime risk of breast cancer 20%, BRCA mutation
SCREENING AVERAGE-RISK OR LOW-
RISK WOMEN carriers, first-degree relatives of BRCA mutation
carriers who remain untested, women with a history
Women who have less than 15% lifetime risk of of mediastinal irradiation be-tween the ages of 10
breast cancer should continue to be offered and 30, and women with certain genetic syndromes
screening mammography annually starting at the (Li-Fraumeni, Cowden, Bannayan-Riley-
95
age of 40 per ACR guidelines. The ACS and the Ruvalcaba). Many statistical models have been
USPSTF, who advise routinely starting screening developed to assess breast cancer risk, such as the
at a later date (45–50), acknowledge that the Gail and modified Gail models, Claus, BOADICEA
most lives are saved from breast cancer when (Breast and Ovarian Analysis of Disease Incidence
screening starts at 40 and is performed annu- and Carrier Estima-tion Algorithm), Tyrer-Cuzick
ally.5,77 Women of average or low risk require no (TC), and BRCAPRO. Existing models have been
additional supplemental screening in addition to calibrated to estimate population risk but
mammography, although the NCCN recommends demonstrate only moderate ac-curacy in
that tomosynthesis be considered (Category 1 discriminating each woman’s individual risk.
105
To
recommendation) in all women starting at 40. 81 determine eligibility for screening breast MR
The ACS and NCCN recommend against MR imaging, the ACS specifically recommends
using BRCAPRO or TC or other models that incor- harms of screening mammography, resulting in hotly
porate first-degree and second-degree relatives to debated controversies. Breast cancer–spe-cific
95,106 mortality reduction is the primary benefit of
estimate breast cancer risk. The ACS recom-
mends against using models with limited family screening mammography, but not the only one.
history input (eg, Gail or modified Gail). Earlier detection and treatment of breast cancers
results not only in decreased breast cancer deaths
but also decreased treatment-related morbidity; that
is, fewer mastectomies and less frequent and less
The ACS recommends annual screening 108,109
mammography and supplemental screening MR toxic chemotherapy. Women diag-nosed with
imaging for the following women: localized breast cancer commonly have the option of
breast-conserving therapy, which is associated with
Estimated lifetime risk of breast cancer 20% few surgical side effects and postoperative upper
BRCA mutation carriers body impairments, less chronic pain, better body
110–112
First-degree relatives of BRCA mutation car- image, and less psycho-logical distress.
riers who remain untested Women with localized dis-ease are more likely to be
eligible for sentinel lymph node biopsy, which
Mediastinal irradiation between the ages of 10
and 30 compared with axillary dissection, is associated with
less upper body morbidity and a lower risk of
Certain genetic syndromes 113
lymphedema. Smaller and less advanced cancers
can be effec-tively treated without chemotherapy,
which has a broad range of side effects, including
The NCCN guidelines mirror the ACS and cardiac toxicity, premature menopause, and an
114–116
include the recommendation to start MR imaging increased risk of blood disorders.
at age 25 and mammography at age 30, or 10 “Harms” of screening mammography include
years before the first-degree relative was false-positive results and associated anxiety, over-
diagnosed, whichever comes later.95 If a woman diagnosis and overtreatment, and radiation risk.
is unable to undergo breast MR imaging (eg, Before considering each individually, it is important
secondary to pacemaker or other implantable to note that both false positives and overdiagnosis
non–MR imaging compatible device, prior are a risk of any and all screening tests. Neither is
contrast anaphylaxis, or severe claustrophobia unique to screening mammography.
not responsive to treat-ment), she may be offered
whole breast screening ultrasound as an adjunct
When to Begin and End Screening
to mammography.76 Screening ultrasound does
Mammograms and at What Frequency
not add value or incre-mental cancer detection in
women who are already receiving both annual Patients and clinicians grapple with 3 possible ages
mammography and MR imaging.52,54,107 (40, 45, and 50) at which to begin screening
mammography and 2 possible frequencies (annual
or biennial) with several different permutations
Screening ultrasound does not add value or in- based on the ACR, ACS, and USPSTF guidelines
cremental cancer detection in women who are (see Table 2). All 3 guidelines recognize that annual
already receiving both annual mammography and mammography should remain an option for each
MR imaging.
woman starting at the age of 40 because all 3
organizations acknowledge that annual screening
mammography beginning at age 40 saves the most
No data or specific recommendations exist lives from breast cancer. Annual screening
regarding the best way to schedule annual mammography of women ages 40 to 84 prevents
mammography and MR imaging. As a result, more deaths from breast cancer (39.6% mortality
some high-risk women choose to obtain reduction) than biennial screening of women 50 to
mammography and MR imaging around the same 74 years old (which has only a 23.2% mortality
time, whereas others choose to alternate 117
mammography and MR imaging every 6 months. reduction). Rapidly growing cancers may become
lethal in the interval between screening rounds, so
an increased screening frequency has the potential
CONTROVERSIES REGARDING SCREENING
to detect more aggressive tumors before lethality.
MAMMOGRAPHY IN AVERAGE-RISK WOMEN
Premen-opausal women diagnosed with breast
Benefits and “Harms” of Screening
cancer on biennial screening mammography (23–26
Individuals and different professional organiza- months)
tions disagree about the relative benefits and
1156 Niell et al
are 21% to 28% more likely to have larger tumors Although false-positive mammograms are a
or higher-stage tumors compared with premeno- downside to screening, most women recalled
pausal women with breast cancer detected at from screening mammography require only addi-
annual (11–14 months) screening.118 tional imaging. Women are willing to tolerate far
higher false-positive rates than actually occur in
clinical practice, suggesting that the “harm” of
Premenopausal women diagnosed with breast false positives may be overemphasized.121
cancer on biennial screening mammography are
significantly more likely to have larger tu-mors or Overdiagnosis
higher-stage tumors compared with
premenopausal women with breast cancer Overdiagnosis is defined as a diagnosis by
detected at annual screening. screening of a cancer that never would have
become symptomatic in the woman’s lifetime or
never would have been detected if screening had
not taken place. The conversation regarding over-
The debate to begin screening at age 40 or 50 ex- diagnosis largely pertains to DCIS, as nonprogres-
ists because age 50 was chosen as a surrogate for sive invasive disease has not to our knowledge been
menopause, and age-stratified analyses (40–49 vs
documented in the peer-reviewed literature.
>50) within individual studies were underpowered to
Overdiagnosis and overtreatment of DCIS remain
detect significant mortality reduction in younger
controversial; however, detection and treatment of
women. After combining data from multiple RCTs, a
DCIS has been shown to decrease subsequent inva-
meta-analysis showed that screening mammog-
sive malignancies. A recent study of more than 5
raphy decreases breast cancer deaths by 18% to
million women who underwent screening mammog-
29% in women ages 40 to 49, similar to breast can-
119
raphy demonstrated that for every 3 screen-detected
cer mortality reduction in women older than 50. cases of DCIS, there was 1 fewer invasive interval
Approximately 1 in 6 women will be diagnosed with 122
breast cancer in the subsequent 3 years.
breast cancer before the age of 50, and 40% of the
person-years of life lost from breast cancer deaths The USPSTF acknowledged that “methods for
2 estimating overdiagnosis at a population level are
are in women diagnosed in their 40s or younger. In not well established” and because of the “lack of
part because the absolute risk of devel-oping breast consensus concerning the optimal method for
cancer within the next 5 years is similar in women calculating the magnitude of overdiagnosis,” the
ages 45 to 49 (0.9%) and 50 to 54 (1.1%) but lower USPSTF acknowledged a very wide range of esti-
in women ages 40 to 44 (0.6%), the ACS suggested mates in the available literature (0% to 54%) but
45 as an alternative age criterion to begin screening 77,123
emphasized an estimate of approximately 20%.
mammography in 2015 despite the lack of difference
5 In studies with adequate adjustment for confounders
in mortality reduction. and baseline incremental increase in breast cancer
incidence, the frequency of overdiag-nosis is
124
False-Positive Mammograms estimated at 1% to 10%. Regardless of the
frequency of overdiagnosis, an “overdiag-nosed”
A “false positive” is a test result that suggests the
cancer will persist on imaging regardless of
presence of a disease when the disease is not pre-
screening interval or age at initial screening.
sent. For women who begin annual screening
Decreasing the screening frequency and delaying
mammography at age 40, the cumulative probabil-ity
onset of screening (from 40 to 45 or 50) will delay
of a false-positive recall over a 10-year period is
120 the timing of overdiagnosis but will not decrease the
61%. On average, an individual woman ages 40 degree of overdiagnosis. Therefore, overdiag-nosis
to 49 who undergoes annual screening mammog- should not be used to determine when to start
raphy will experience 1 false-positive mammo-gram screening or how often to screen.
every 10 years and 1 false-positive biopsy every 149
117
years. Biennial screening reduces false-positive
mammograms by one-third compared with annual Decreasing screening frequency or delaying
screening because of the smaller number of onset of screening (from age 40 to later) will not
mammograms performed.
85,120 decrease the degree of overdiagnosis.
On average, an individual woman aged 40 to 49

who undergoes annual screening mammog- Radiation Risk
raphy will experience 1 false-positive mammo-
gram every 10 years. The 2016 USPSTF recommendations state that
“.radiation-induced breast cancer and resulting
death can also occur, although the number of late-stage breast cancer decreased 37% in 2007
both of these events is predicted to be low.”77 At to 2009 compared with 1977 to 1979 with a
most, 2 to 11 deaths due to radiation-induced concomitant increase in early-stage breast can-
cancer may occur per 100,000 women cers.126 Publications that claim that screening
screened125 and additional publications estimate mammography has not resulted in decreased
the risk of a fatal radiation-induced breast cancer late-stage cancers have consistently failed to ac-
due to screening mammography for a woman in count for the underlying interval increase in
her forties is 1 in 76,000 to 97,000 and too large breast cancer incidence.129,130
to estimate for a women in her eighties.117
SUMMARY
False-Negative Mammograms and “False
Reassurance” The ACS, ACR, and the USPSTF, as well as every
medical professional organization, to our knowl-
Mammograms do not detect all breast cancers
edge, agree that screening mammography signifi-
and should not be used to tell a woman that she
cantly decreases breast cancer mortality. Although
does not have breast cancer. The probability of a
screening mammography is covered as a preventive
missed breast cancer increases with age, aver-
care benefit without cost sharing un-der the Patient
aging once every 667 years for a woman older
Protection and Affordable Care Act, nearly one-third
than 70 and once every 1000 years for a woman
of US women older than 40 are not receiving regular
aged 40 to 49.117 screening mammograms. In 2013, fewer than 66%
of women older than 40 in the United States had a
Decreased Breast Cancer Mortality: Is It
screening mammogram in the preceding 2 years,
Secondary to Screening or Improved
compared with fewer than 69% of women older than
Treatment?
131
50. The lack of a na-tional consensus on
The incidence of breast cancer has been steadily screening frequency and age to begin screening
increasing in the United States, with an annual may contribute to the low compliance. After
percent change of 0.8% to 2.3% per year with similar reviewing this article, clinicians should feel
126
increases observed in other countries. However, empowered to engage women in informed
between 1990 and 2000, breast cancer mortality in discussions regarding the pros and cons of regular
women decreased 24% in the United States (see screening mammography, as well as supplemental
Fig. 1). The decrease in breast cancer mortality screening in high-risk women. By educating our
despite increasing incidence is attribut-able to a patients on the importance of breast cancer
combination of screening mammography and screening and early detection, we can continue to
127
improved treatment options. American men, who decrease the number of lives un-necessarily lost to
presumably have access to similar treatment breast cancer each year.
regimens as women but do not have ac-cess to
screening mammography, had a breast cancer
2
mortality in 2013 which is identical to 1990. In Screening mammography is underused, result-
Sweden, women aged 40 to 69 who un-derwent ing in unnecessary breast cancer deaths.
screening experienced a 44% reduction in breast
cancer mortality, compared with only a 16% mortality
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Screening For Breast Cancer

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Screening for Breast

INTRODUCTION reader will be better equipped to have informed

Disclosure Statement: The authors have nothing to disclose.

Radiol Clin N Am 55 (2017) 1145–1162

Screening for Breast Cancer

Table 1 The most recent RCT in mammography started

Neovascularity causes tumors to enhance, usually

Screening for Breast Cancer

report a 10-minute to 20-minute acquisition time SCREENING BREAST MR IMAGING

Fig. 2. Increased lesion conspicuity

who underwent 3 rounds of annual screening ultra-

Screening breast MR imaging demonstrates high

Disadvantages of breast MR imaging include the

Breast thermography cannot and should

Age to Start How Often Age to Stop Comment

Screening for Breast Cancer

standard digital mammography.92 It should be imaging or supplemental screening in women

SCREENING HIGH-RISK WOMEN

Screening for Breast Cancer

On average, an individual woman aged 40 to 49

33. Brem RF, Lenihan MJ, Lieberman J, et al. Screening

34. Niklason LT, Christian BT, Niklason LE, et al.

38. Zuley ML, Guo B, Catullo VJ, et al. Comparison of

78. Lee CH, Dershaw DD, Kopans D, et al. Breast can-cer

97. Friedlander LC, Roth SO, Gavenonis SC. Results of

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