Breast Cancer Screening

Early detection remains the primary way to prevent the development of life-threatening breast cancer. Breast cancers that are detected when smaller or nonpalpable are more treatable and thus are associated with a more favorable prognosis.

Imaging studies used in breast cancer screening include the following:

• Mammography
• Ultrasonography
• Magnetic resonance imaging (MRI)

The survival benefit of early detection with mammography screening has been demonstrated. However, advances in imaging technology and disagreements over recommended schedules have complicated the issue of screening. As with any cancer screening program, careful consideration must be given to the risks of developing breast cancer as well as the benefits and harms of the screening intervention, along with the cost involved. Breast cancer screening guidelines provide different recommendations for women at average risk versus those with elevated risk; for full discussion of risk calculation, see Breast Cancer Risk Factors.

Early detection is widely endorsed by organizations that issue clinical recommendations for breast cancer care. Many expert groups have offered their recommendations for breast cancer screening, and much of the controversy lies in the fact that there is not a consensus about when to begin and end screening, how often to screen, and by what technique. These groups include the following;

• American Cancer Society (ACS)
• American College of Obstetricians and Gynecologists (ACOG)
• American College of Physicians (ACP)
• American College of Radiology (ACR)
• National Comprehensive Cancer Network (NCCN)
• United States Preventive Services Task Force (USPSTF)

For further information, see Breast Cancer. Also see Breast Lumps in Young Women: Diagnostic Approaches, a Critical Images slideshow, to help manage palpable breast lumps in young women.

For women younger than 40 years at average risk for breast cancer, there have no been randomized studies done to suggest a benefit to screening. The various experts groups have not reached a consensus among them, but several recommend a clinical breast exam (CBE) every 3 years and a discussion about breast awareness (ie, encouraging women to be familiar with their breasts and to promptly report any changes to their health care provider).

For women age 40 years and older who are at average risk for breast cancer, many expert groups recommend CBE annually. With respect to imaging, in the past the most widely recommended screening approach in the United States for this group has been annual mammography, starting at age 40 years.[1] Increasingly, however, guidelines are advising clinicians to discuss the benefits and risks of mammography with patients and offer the option of starting screening at age 40, but do not strongly recommend starting screening until age 45 or 50. Current guidelines also offer conflicting recommendations on whether to perform mammography annually or biennially.

Recommendations regarding discontinuation of mammography vary as well, with both age—typically, 75 years[2] —and life expectancy as criteria. For example, the American College of Radiology recommends annual screening mammography until the life expectancy is less than 5 to 7 years, based on comorbidities.[3]

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.

See the table below.

Table. Guideline Recommendations for Breast Cancer Screening in Women at Average Risk (Open Table in a new window)

USPSTF guidelines

The current guidelines on breast cancer screening from the US Preventive Services Task Force (USPSTF), issued in 2016, include the following recommendations[9, 2] :

• The USPSTF recommends biennial screening mammography for women aged 50 to 74 years

• No requirement for routine screening mammography in women aged 40-49 years (grade C recommendation); the decision to start regular, biennial screening mammography before age 50 years should be an individual one and should take into account patient context, including the patient's values regarding specific benefits and harms

• Insufficient current evidence to assess the additional benefits and harms of screening mammography in women aged 75 years or older

• Insufficient current evidence to assess the additional benefits and harms of either digital mammography or magnetic resonance imaging (MRI) instead of film mammography as a screening modality for breast cancer

• No requirement for clinicians to teach women how to perform BSE (grade D recommendation); this recommendation is based on studies that found that teaching BSE did not reduce breast cancer mortality but instead resulted in additional imaging procedures and biopsies

• Insufficient current evidence to assess the additional benefits and harms of clinical breast examination (CBE) beyond screening mammography in women aged 40 years or older

American Cancer Society guidelines

The 2015 update of the American Cancer Society guidelines includes the following recommendations[4] :

• Women with an average risk of breast cancer should undergo regular screening mammography starting at age 45 years (strong recommendation).
• Women aged 45 to 54 years should be screened annually (qualified recommendation).
• Women 55 years and older should transition to biennial screening or have the opportunity to continue screening annually (qualified recommendation).
• Women should have the opportunity to begin annual screening between the ages of 40 and 44 years (qualified recommendation).
• Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer (qualified recommendation).
• The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age (qualified recommendation).

American College of Obstetricians and Gynecologists guidelines

The 2017 update of the American College of Obstetricians and Gynecologists guidelines on screening in average-risk women includes the following recommendations for practitioners[5] :

• Use shared decision-making to select screening choices
• Clinical breast examination may be offered every 1-3 years for women aged 29-39 years and annually for women aged ≥ 40 years
• Start offering mammography at age 40 years; initiate after counseling, if patient desires
• Recommend starting mammography screening by no later than age 50 years
• Mammography may be annual or biennial; biennial screening is particularly reasonable after age 55 years
• Continue mammography until age 75 years, then discuss discontinuation, with the woman's health status and longevity as considerations

American College of Physicians guidelines

A 2019 guidance statement from the American College of Physicians (ACP), based on a review of existing guidelines, addresses mammography in women at average risk, which is defined as the absence of the following:

• History of breast cancer or previous diagnosis of a high-risk lesion
• Genetic mutations such as BRCA1/2 or another familial breast cancer syndrome
• History of radiation therapy to the chest in childhood

The ACP provides the following  recommendations to clinicians for breast cancer screening in average-risk women, according to age[6] :

• Ages 40 to 49 years: Discuss whether to screen for breast cancer with mammography before  age 50 years. The discussion should include the potential benefits and harms and the woman's preferences. For most women in this age group, the potential harms outweigh the benefits.
• Ages 50 to 74 years: Offer screening for breast cancer with biennial mammography.
• Ages 75 years or older or in women with a life expectancy of 10 years or less: Discontinue screening for breast cancer.
• All ages: Do not use clinical breast examination to screen for breast cancer.

National Comprehensive Cancer Network guidelines

The NCCN on screening in average-risk women includes the following recommendations[8] :

• Clinical breast examinations every 1-3 years from age 25-39, then annually from age 40 on
• Begin annual screening mammography at age 40 years.
• Consider tomosynthesis (three-dimensional mammography)
• Promote breast awareness; breast self-examination is not recommended

NCCN guidelines provide four separate sets of recommendations for women at increased risk, on the basis of personal or family history, These include earlier initiation of mammography, in some cases, and consideration or recommendation of annual MRI. Additional considerations include the following:

• An upper age limit for screening is not yet established. Consider severe comorbid conditions limiting life expectancy (eg, ≤10 years) and whether therapeutic interventions are planned.

• For women with heterogeneous dense breasts and dense breast tissue, recommend counseling on the risks and benefits of supplemental screening.

• Dense breasts limit the sensitivity of mammography and are associated with an increased risk for breast cancer.

• Full-field digital mammography appears to benefit young women and women with dense breasts.

• Multiple studies show that tomosynthesis can decrease callback rates and appears to improve cancer detection. Most studies used double the dose of radiation, but the radiation dose can be minimized by using synthesized 2-D reconstruction.

• Hand-held or automated ultrasound can increase cancer detection, but may increase recall and benign breast biopsies.

• Current evidence does not support the routine use of molecular imaging (eg, breast-specific gamma imaging, sestamibi scan, or positron emission mammography) as screening procedures, but emerging evidence suggests that these tests may improve detection of early breast cancers in women with mammographically dense breasts. However, the whole-body effective radiation dose with these tests is 20 –30 times higher than that of mammography.

• Current evidence does not support the routine use of thermography or ductal lavage as screening procedures.

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). Even with appropriate training, however, BSE has not been found to reduce breast cancer mortality, and it has been found to increase the number of unnecessary breast biopsies.[11] Consequently, the majority of the expert groups have withdrawn their support for BSE and instead recommend discussions about the benefits and limitations of this technique or a more general education about breast self-awareness.[8]

For example, ACOG distinguishes between BSE, which it does not recommend, from breast self-awareness, which it endorses.[5]  Unlike BSE, breast self-awareness does not involve routine or systematic breast self-examination for the purpose of detecting breast cancer. Rather, it is a woman's attunement to the normal appearance and feel of her breasts, so that she can notify her health care provider if she experiences breast changes such as pain, a mass, new onset of nipple discharge, or redness.[5]

With increasing improvements in treatment regimens for early, localized disease, CBE, particularly among women younger than 40 years, continues to be recommended by many groups, including ACOG and NCCN. 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.

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 lesions before they become palpable by clinical breast examination (CBE) and, on average, 1-2 years before being found 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).[12]

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

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.

Although mammography remains the most cost-effective approach for breast cancer screening, it is far from a perfect screening test. The accuracy of screening mammography increases with increasing patient age, in tandem with the increasing incidence of breast cancer. Mammography has a sensitivity of 76.5% and a specificity of 87.1% for women younger than 40 years.[13] By comparison, in women 50 to 59 years old, the sensitivity of screening mammography is 77.3% and the specificity is 98.7%.[14] In women older than 80 years, mammography has a sensitivity of 86% and a specificity of 94%.[15]

A retrospective trend analysis compared rates of breast cancer mortality in pairs of neighboring European countries where mammography screening had been implemented at different times. Findings suggest that mammography screening has little detectable impact on mortality due to breast cancer.[16]

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.

In the United States, approximately 9.5% of screening mammograms yield false-positive results; of US women screened annually for 10 years, approximately 50% will experience a false positive, and 7-17% of those will undergo breast biopsies.[17] False positives occur most commonly with first mammograms; when prior mammograms are available for comparison, the likelihood of a false positive decreases by about 50%.[18]

False-negative rates of screening mammography (ie, cases in which invasive breast cancer is present but undetected by mammography) range from 6% to 46%.[17] Possible causes for missed breast cancers include the following:

• Dense parenchyma obscuring a lesion
• Poor positioning or technique
• Perception error
• Incorrect interpretation of a suspect finding
• Subtle features of malignancy
• 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.[19] 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 a benign lesion.

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 pose 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.

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, ultrasonography is limited by a number of factors, most notably by a 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.[20, 21]

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).[22] 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.)

In 2012, the FDA approved the first ultrasound system, the somo-v Automated Breast Ultrasound System (ABUS), for breast cancer screening specifically in women with dense breast tissue.[23] ABUS is indicated as an adjunct to standard mammography for women with a negative mammogram, no breast cancer symptoms and no previous breast intervention such as surgery or biopsy.

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.

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, in younger women, and in women with dense breasts. 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.[24]

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.[25] 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.

In a study of 475 asymptomatic women with dense breasts who had negative/benign digital breast tomosynthesis examinations who underwent supplementary screening with abbreviated breast MRI, 420 women (88.4%) had negative/benign findings, 13 (2.7%) were recommended for short-interval follow-up, and 42 (8.8%) were recommended for biopsy. Of 39 completed biopsies, 12 (38.9%) identified malignancies: 7 invasive carcinomas and 5 ductal carcinoma in situ. An additional patient was diagnosed with invasive ductal carcinoma by biopsy recommended at 6-month follow-up. The positive predictive value 2 (PPV2) was 28.6% (12 of 42 recommended biopsies); PPV3 was 30.8% (12 of 39 completed biopsies). The researchers concluded that additional evaluation is warranted.[26]

For more information, see Magnetic Resonance Mammography.

Screening criteria

The American Cancer Society (ACS) has established criteria for using breast MRI screening.[27] Based on evidence from nonrandomized trials and observational studies, the ACS recommends annual breast MRI screening in addition to mammography 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

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 (LCIS), atypical lobular hyperplasia (ALH), or 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. For women who have a 15-20% lifetime risk of developing breast cancer, the ACS found insufficient evidence to recommend screening MRI.

The National Comprehensive Cancer Network (NCCN) guidelines on MRI screening differ from those of the ACS as follows[8] :

• Annual MRI screening recommended in first-degree relatives of a BRCA carrier, but untested (encourage genetic testing before MRI)

• Annual MRI screening is recommended for women with lifetime risk 20% or greater, as defined by models that are largely dependent on family history. Encourage genetic testing for first-degree relatives. If testing declined, recommend MRI.

• Annual MRI screening is recommended for women who received radiation therapy to the chest when aged 10-30 years.

• Annual MRI screening may be considered for women with a history of LCIS and ALH/ADH whose lifetime risk is ≥20%.

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