Breast Cancer Screening

Overview

Early
detection of remains the primary defense available to patients in
preventing the development of life-threatening breast cancer. Breast
tumors that are smaller or nonpalpable are more treatable when detected
and thus are associated with a more favorable prognosis. The survival
benefit of early detection with mammography screening has been
demonstrated. Consequently, early detection is widely endorsed by
organizations that issue clinical recommendations for breast cancer
care. However, advances in imaging technology and disagreements over
recommended schedules have complicated the issue of screening. For further information, see Breast Cancer and Breast Cancer Risk Factors.
Next Section: Guidelines



Guidelines

For
women younger than 40 years, monthly breast self-examination (BSE) and
clinical breast exams every 3 years have been recommended, beginning at
age 20 years. The most widely recommended screening approach in the
United States has been annual mammography beginning at age 40 years.^[1] However, in November 2009, the US Preventive Services Task Force (USPSTF) issued updated breast cancer screening guidelines that recommend against routine mammography before age 50 years. Instead,
for women aged 40 to 49 years, the USPSTF suggests that the decision to
start regular screening mammography be individualized and should
include the patient's values regarding specific benefits and harms.^[2] In addition, rather than annual screening, the USPSTF guidelines recommend that screening mammography be performed biennially. The
USPSTF concludes that there is currently insufficient evidence to
assess the additional benefits and harms of screening mammography in
women 75 years or older and thus recommends stopping screening at age 74
years.^[2] The
USPSTF recommends against teaching BSE, based on studies that found
that teaching BSE did not reduce breast cancer mortality but instead
resulted in additional imaging procedures and biopsies.^[2] However,
the American College of Obstetricians and Gynecologists (ACOG)
continues to recommend counseling patients that BSE has the potential to
detect palpable breast cancer and can be performed.^[3] The USPSTF recommendations/findings are summarized as follows:

• No requirement for clinicians to teach women how to perform BSE (Grade D recommendation)
  
• No
  requirement for routine screening mammography in women aged 40 to 49
  years (Grade C recommendation); 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
  
• Biennial screening mammography for women between the ages of 50 and 74 years (Grade B recommendation)
  
• Insufficient current evidence to assess the additional benefits and harms of screening mammography in women 75 years or older
  
• Insufficient
  current evidence to assess the additional benefits and harms of
  clinical breast examination (CBE) beyond screening mammography in women
  40 years or older
  
• Insufficient
  current evidence to assess the additional benefits and harms of either
  digital mammography or MRI instead of film mammography as screening
  modalities for breast cancer
  

In response, ACOG is
evaluating the USPSTF guidelines in detail but for the present it
continues to recommend adherence to the current ACOG guidelines. These
include screening mammography every 1-2 years for women aged 40-49 years
and screening mammography every year for women 50 years or older.^[3] The
ACOG notes, however, that because of the USPSTF downgrading, some
insurers may no longer cover some of these imaging studies. Although
mammography guidelines have been in place for over 30 years, 20-30% of
women still do not undergo screening as indicated. The 2 most
significant factors in determining whether a woman undergoes mammography
are physician recommendation and access to health insurance. Non-white
women and those of lower socioeconomic status remain less likely to
obtain mammography services, and these women are more likely to present
with life-threatening, advanced-stage disease.
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Self-examination and Clinical Examination

Breast
self-examination (BSE) and clinical breast examination (CBE) are
inexpensive and noninvasive procedures for the regular examination of
breasts (ie, monthly BSE and annual CBE). Evidence supporting the
effectiveness of these 2 screening methods is controversial and largely
inferred. Even with appropriate training, BSE has not been found
to reduce breast cancer mortality. However, with increasing improvements
in treatment regimens for early, localized disease, BSE and CBE,
particularly among women younger than 40 years, continues to be
recommended by many health care organizations. Randomized
clinical trial results support combining CBE with mammography to enhance
screening sensitivity, particularly in younger women in whom
mammography may be less effective and in women who receive mammograms
every other year as opposed to annually.
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Mammography

Mammography
is a special type of low-dose x-ray imaging used to create detailed
images of the breast. Mammography is currently the best available
population-based method to detect breast cancer at an early stage, when
treatment is most effective. Mammography can demonstrate
microcalcifications smaller than 100 µm; it often reveals a lesion
before it is palpable by clinical breast examination (CBE) and, on
average, 1-2 years before noted by breast self-examination (BSE). An
estimated 48 million mammograms are performed each year in the United
States. The US Preventive Services Task Force (USPSTF) estimates
the benefit of mammography in women aged 50-74 years to be a 30%
reduction in risk of death from breast cancer. For women aged 40-49
years, the risk of death is decreased by 17%. There are 2 types
of mammography examinations: screening and diagnostic. Screening
mammography is done in asymptomatic women. Diagnostic mammography is
performed in symptomatic women (eg, when a breast lump or nipple
discharge is found during self-examination or an abnormality is found
during screening mammography). This examination is more involved,
time-consuming, and expensive than screening mammography and is used to
determine the exact size and location of breast abnormalities and to
image the surrounding tissue and lymph nodes. Women with breast implants
or a personal history of breast cancer will usually require the
additional views used in diagnostic mammography. The American College of Radiology (ACR) has established the Breast Imaging Reporting and Data System (BI-RADS)
to guide the breast cancer diagnostic routine. BI-RADS is the product
of a collaborative effort between members of various committees of the
ACR in cooperation with the National Cancer Institute (NCI), the Centers
for Disease Control and Prevention (CDC), the FDA, the American Medical
Association (AMA), the American College of Surgeons (ACS), and the
College of American Pathologists (CAP).^[4] The
BI-RADS system includes categories or levels that are used to
standardize interpretation of mammograms among radiologists. For
referring physicians, the BI-RADS categories indicate the patient’s risk
of malignancy and recommend a specific course of action. Of all
of the screening mammograms performed annually, approximately 90% show
no evidence of cancer. On necessary further diagnostic testing,
approximately 2% of all screening mammograms are shown to be abnormal
and require biopsy. Among cases referred for biopsy, approximately 80%
of the abnormalities are shown to be benign, and 20% are shown to be
cancerous. See Mammography in Breast Cancer for more information.
Limitations of techniques

Although
mammography remains the most cost-effective approach for breast cancer
screening, the sensitivity (67.8%) and specificity (75%) are not ideal.
Mammography combined with clinical breast examination (CBE) slightly
improves sensitivity (77.4%), with a modest reduction in specificity
(72%). Mammographic sensitivity for breast cancer declines
significantly with increasing breast density, and the risk of breast
cancer is higher in women with dense breasts. Hormonal status has no
significant effect on the effectiveness of screening independent of
breast density. Mammography uses low-dose ionizing radiation,
which may be harmful to the patient. Nevertheless, the benefits of
mammography far outweigh the risks and inconvenience. False-positive and false-negative results

False-positive
results may arise when benign microcalcifications are regarded as
malignant. Tissue summation shadows may appear as local parenchymal
distortion; this may erroneously be called malignant tissue. A benign,
circumscribed lesion may show signs suggestive of malignancy, along with
other findings, such as an irregular border and no halo sign. According
to data from the Breast Cancer Detection Demonstration Project (BCDDP),
the false-negative rate of mammography is approximately 8-10%. About
1-3% of women with a clinically suspicious abnormality, a negative
mammogram, and a negative sonogram may still have breast cancer. Possible
causes for missed breast cancers include dense parenchyma obscuring a
lesion, poor positioning or technique, perception error, incorrect
interpretation of a suspect finding, subtle features of malignancy, and
slow growth of a lesion. Birdwell et al performed a multicenter
study and found that on previous mammograms with missed cancers, 30% of
the 115 lesions were calcifications, with 49% (17 of 35) clustered or
pleomorphic.^[5] Approximately
70% were mass lesions, with 40% spiculated or irregular. For
calcifications and masses, the most frequently suggested reasons for
possible miss were dense breasts (34%) and distracting lesions (44%). Some cancers (eg, mucinous carcinomas) may have well-defined borders and mammographic features suggestive of benignancy.
Other uses of mammography in breast cancer

A
ductogram, or galactogram, is sometimes helpful for determining the
cause of nipple discharge. In this specialized examination, a fine
plastic tube is placed into the opening of the duct in the nipple. A
small amount of contrast medium is injected, which outlines the shape of
the duct on a mammogram and shows whether a mass is present inside the
duct.
Women with breast implants

Women with breasts
augmented by implants may be a special challenge. Specific 4-view
mammograms may be performed to evaluate the breasts; MRI may be
especially useful for detecting breast cancer and silicon implant rupture in this group of patients. See Postsurgical Breast Imaging for more information.
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Ultrasonography

Ultrasonography
has become a widely available and useful adjunct to mammography in the
clinical setting. Ultrasound is generally used to assist the clinical
examination of a suspicious lesion detected on mammography or physical
examination. As a screening device, ultrasound is limited by a number of
factors, most notably by the failure to detect microcalcifications and
by poor specificity (34%). Originally, ultrasonography was used
primarily as a relatively inexpensive and effective method of
differentiating cystic breast masses, which did not require sampling,
from solid breast masses that were usually examined with biopsy; in many
cases, the results of these biopsies were benign. However, it is now
well established that ultrasonography also provides valuable information
about the nature and extent of solid masses and other breast lesions. This
imaging technique is also useful in the guidance of biopsies and
therapeutic procedures; research is currently under way to evaluate its
role in cancer screening. Although mammography is an effective
screening tool, data suggest that it is often less sensitive in
detecting cancer in mammographically dense breast tissue. Kolb et al and
Buchberger et al found that when performed carefully, ultrasonography
may be useful in detecting occult breast cancer in dense breasts.^{[6, 7]} Ultrasonography
is generally acknowledged to be a highly operator-dependent modality
that requires a skilled practitioner, high-quality examinations, and
state-of-the-art equipment. In view of the results of these studies, a
prospective, multicenter study is clearly needed to examine the role of
this imaging modality in breast cancer screening. A large
multicenter study supported by the Avon Foundation and the National
Institutes of Health (NIH) was created through the American College of
Radiology Imaging Network (ACRIN).^[8] In
this project, a protocol to assess the efficacy of screening breast
ultrasonography is being implemented in 14 imaging centers to better
define the role of this modality in breast cancer screening. (More
information is available on the ACRIN Web site.) Currently,
it is recommended that ultrasonographic screening for breast disease be
reserved for special situations, such as for highly anxious patients
who request it and for women who have a history of mammographically
occult carcinoma. See Ultrasonography in Breast Cancer for more information.
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Magnetic Resonance Imaging

In
an effort to overcome the limitations of mammography and
ultrasonography, MRI has been explored as a modality for detecting
breast cancer in women at high risk and in younger women. A combination
of T1, T2, and 3-D contrast-enhanced MRI techniques has been found to be
highly sensitive (approximating 99% when combined with mammography and
clinical breast examination) to malignant changes in the breast. MRI has been demonstrated to be an important adjunct screening tool for women with BRCA1 or BRCA2
mutations, identifying cancers at earlier stages. However, breast MRI
has limited use as a general screening tool, with a 10-fold higher cost
than mammography and poor specificity (26%), resulting in significantly
more false-positive reads that generate significant additional
diagnostic costs and procedures.According to the only study conducted to date using a control group, annual MRI-based screening among BRCA1 and BRCA2
carriers resulted in a significant 70% reduction in the hazard of
developing stage II-IV (large or node-positive) invasive breast cancers
(HR, 0.30; 95% CI, 0.12-0.71) compared to BRCA1 and BRCA2 carriers not undergoing annual MRI examinations.^[9] Importantly,
while the comparison group was instructed to undergo routine
mammography screening, the majority of cancers were reported as
self-detected. While these findings are not from a randomized setting
and may suffer from unmeasured confounding that impacted the estimated
effect of MRI, they provide support from a large population of BRCA1 and BRCA2 carriers for the beneficial use of MRI for the earlier detection of cancers.Remaining
unclear is the overall impact of earlier detection in this patient
population on survival; a question that could not be addressed due to
short follow-up. For more information, see Magnetic Resonance Mammography.
American Cancer Society MRI screening criteria

The American Cancer Society (ACS) has established criteria for using breast MRI screening.^[10] Based
on evidence from nonrandomized trials and observational studies, the
ACS recommends annual breast MRI screening in patients with the
following risk factors:

• BRCA mutation
  
• First-degree relative of BRCA carrier but untested
  
• Lifetime risk approximately 20-25% or greater, as defined by BRCAPRO or other risk models
  

Based
on evidence of lifetime risk of breast cancer, the ACS recommends
annual breast MRI screening in patients with the following risk factors:

• Radiation to chest when aged 10-30 years
  
• Li-Fraumeni syndrome and first-degree relatives
  
• Cowden and Bannayan-Riley-Ruvalcaba syndromes and first-degree relatives
  

The ACS found insufficient evidence to recommend for or against MRI screening in patients with the following risk factors:

• Lifetime risk 15-20%, as defined by BRCAPRO or other risk models
  
• Lobular carcinoma in situ or atypical lobular hyperplasia (ALH)
  
• Atypical ductal hyperplasia (ADH)
  
• Heterogeneously or extremely dense breast on mammography
  
• Personal history of breast cancer, including ductal carcinoma in situ
  

The
ACS does not recommend the use of breast MRI in women who have a less
than 15% lifetime risk of breast cancer. For those with average risk, a
combination of clinical breast examinations and yearly mammograms is
recommended.
Advantages of MRI

The many advantages of
breast MRI over conventional breast imaging for the detection of
malignancy have become apparent with increasing clinical experience.
These advantages include the following:

• No ionizing radiation
  
• All imaging planes possible
  
• Capability of imaging the entire breast volume and chest wall
  
• Superb 3-D lesion mapping with techniques such as maximum intensity projection (MIP) slab 3-D reconstruction
  
• Greater than 90% sensitivity to invasive carcinoma
  
• Detection of occult, multifocal, or residual malignancy
  
• Accurate size estimation for invasive carcinoma
  
• Good spatial resolution
  
• Ability to image regional lymph nodes (although accurate staging remains problematic)
  

Disadvantages of MRI

The widespread use of breast MRI for the detection of breast malignancy also has many disadvantages, as follows:

• High equipment and examination costs
  
• Limited scanner availability
  
• Need for the injection of a contrast agent
  
• No standard technique
  
• Poor throughput compared with that of ultrasonography or mammography
  
• Large number of images
  
• Long learning curve for interpretation
  
• False-positive enhancement in some benign tissues (limited specificity)
  
• Variable enhancement of in situ carcinoma
  
• A 5% incidence of slowly or poorly enhancing invasive carcinomas
  

Contraindications to MRI

Conversely,
in a number of situations, MRI is essentially contraindicated, usually
because of physical constraints that prevent adequate patient
positioning. These constraints include the following: Contraindication to gadolinium-based contrast media (eg, allergy, pregnancy)

• Patient's inability to lie prone
  
• Marked kyphosis or kyphoscoliosis
  
• Marked obesity
  
• Extremely large breasts
  
• Severe claustrophobia
  

Relative
contraindications also exist. These are essentially based on the high
sensitivity but limited specificity of the technique. MRI may not be
useful for the following:

• Cancer-phobic patients
  
• Assessment of mammographically detected microcalcifications