MRI Breast Cancer Screening

Optimizing MRI Breast Cancer Screening: A Multidisciplinary Perspective CME

Therese B. Bevers, MD; Parijatham S. Thomas, MD; Habib Rahbar, MD; Erin I. Neuschler, MD



Breast Cancer Screening Using MRI Technology

Although mammography remains the gold standard for detecting breast cancer, it has been reported to miss up to 40,000 to 45,000 breast cancers each year.[1] It therefore may not be a sufficient screening tool for women at high risk of developing breast cancer (≥20% risk). Clinical trials have shown magnetic resonance imaging (MRI) to significantly improve the detection of cancers that are otherwise clinically, mammographically, and sonographically occult, leading the American College of Radiology (ACR) and the American Cancer Society (ACS) to recommend the use of breast screening MRI as an adjunct to mammography to improve breast cancer surveillance in high-risk women.[2-4] There are currently no recommendations for or against breast MRI in women at mild or moderately increased risk (15%-20%) of developing breast cancer because the benefits in this population remain unclear.[3]


Clinical Utility of MRI vs Mammography

Mammograms use low doses of radiation to produce x-ray images of the breast. Because x-rays are not able to effectively penetrate dense breast tissue, these images can be more difficult to obtain and read when patients have dense breasts. Compared with mammography, MRI is more sensitive in detecting breast abnormalities. It uses magnetic fields to produce cross-sectional images of soft-tissue structures. The contrast between lesions and normal tissues of the breast, such as adipose and fibroglandular, depends on the mobility and magnetic environment of the hydrogen atoms in the water and fat of these tissues. Gadolinium-based contrast agents (GBCAs) are injected intravenously to improve detection of cancers and other lesions, and studies have shown contrast-enhanced MRI to have a high sensitivity for detecting breast cancers,[5-7] making it a beneficial screening tool for women who are at high risk of developing breast cancer, particularly in the setting of dense breast tissue.

Several large, prospective, nonrandomized studies have been conducted worldwide to evaluate the efficacy of adding breast screening MRIs to annual mammography in women at high risk of developing breast cancer (Table 1).[8-12] These studies included women with BRCA1 or BRCA2 gene mutations or a strong family history of breast cancer. Although patient population characteristics and techniques in obtaining breast MRI varied between studies, all studies showed MRI to have a higher sensitivity in detecting breast cancer compared with mammography. Of the studies that had more than 1 round of screening, interval cancer rates were less than 10%.[8-10,12]

Table 1. Summary of 5 Published Breast MRI Screening Studies[4]
The Netherlands Canada United Kingdom Germany United States
Sensitivity (%)
MRI 80 77 77 91 100
Mammogram 33 36 40 33 25
Ultrasound N/A 33 N/A 40 N/A
Specificity (%)
MRI 90 95 81 97 95
Mammogram 95 >99 93 97 98
Ultrasound N/A 96 N/A 91 N/A

N/A = not applicable.
From Saslow D, et al.[4]

Although breast MRI can detect smaller tumors than mammography, it has limitations. Due to its lower specificity and higher sensitivity, callback rates for additional imaging and biopsy have been higher with MRI in high-risk populations, ranging from 8% to 17% for imaging and 3% to 15% for biopsy.[8-12] However, recall rates decreased with subsequent rounds of screening. Increased callback and biopsy rates can lead to increased patient anxiety, which has the potential to adversely affect women's future compliance with screening, but it can also increase the number of detected cancers.
Cost-Effectiveness of Breast MRI

The cost-effectiveness of adding breast MRI to annual mammography has been evaluated in different high-risk cohorts. Plevritis and colleagues reported that the addition of breast MRI was cost-effective in BRCA1 and BRCA2 mutation carriers but that the cost per quality-adjusted life year (QALY) was greater in women with BRCA1 mutations and varied greatly with age, though the cost benefits were greatest in patients aged 40 to 49 years for both mutation types.[13] The increased cost savings in the BRCA1 group was attributed to these mutations having a higher risk for cancer, including more aggressive cancers, compared with BRCA2 mutations.[13,14]

A 2014 study by Ahern and colleagues evaluated the cost-effectiveness for various schedules integrating screening MRI with mammography in women with a strong family history of breast cancer and a lifetime risk of 25% or higher.[15] Based on current MRI costs and an incremental cost-effectiveness ratio of $100,000 per QALY, they found the most cost-effective strategy was to stagger MRI and mammography plus clinical breast exam every year from age 30 to 74 for women who had a 25% lifetime risk of breast cancer. For those with a 50% lifetime risk, the recommended strategy was to follow the same screening protocol but to stagger these examinations every 6 months, provided there was a 70% reduction in MRI costs. At 75% risk, the recommended strategy became biennial MRI combined with mammography plus clinical breast exam every 6 months.[15] Although screening MRIs may eventually become routine in breast cancer surveillance, their high cost is currently a major factor restricting their use to those deemed to be at sufficiently high risk of developing breast cancer.
Identifying the High-Risk Patient

Based on the current literature, the ACS has established guidelines recommending breast MRI as an adjunct to annual mammography in specific groups of women at high risk (≥20% risk) of developing breast cancer (Table 2).[3] Identifying these high-risk patients requires careful consideration of several key risk factors, including a strong family history of breast cancer, the presence of BRCA1 and/or BRCA2 gene mutations, and exposure to certain types of radiation.

Table 2. American Cancer Society's Recommendations for Annual Breast Screening MRIs
Patients Who Should Receive Annual MRI Screenings

Have BRCA1 or BRCA2 mutations
First-degree relative is a BRCA carrier, but patient's BRCA status is unknown
Lifetime risk of breast cancer is ≥20%, as determined by risk assessment tools based predominantly on family history
History of chest irradiation between the ages of 10 and 30
Have Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or have a first-degree relative with one of these syndromes

Patients With Insufficient Evidence to Make Recommendation for or Against Annual MRI Screenings

Lifetime risk of breast cancer between 15% and 20%, as defined by risk assessment tools based predominantly on family history
Heterogeneously or extremely dense breasts on mammography
History of benign breast lesions that increase the risk of breast cancer, including lobular carcinoma in situ, atypical lobular hyperplasia, and atypical ductal hyperplasia
History of breast cancer, including ductal carcinoma in situ

Patients Who Should Not Receive MRI Screenings

Lifetime risk of breast cancer is <15%

Family History

Because breast cancer is the most common cancer among women, many women in the general population will have at least 1 relative with breast cancer. However, this alone does not confer an increased risk of developing breast cancer because only 5% to 10% of all breast cancers are thought to be hereditary.[3] These heritable cases are attributable to mutations in several highly penetrant susceptibility genes, of which BRCA1 and BRCA2 are currently the best recognized. Women who carry a genetic mutation in these genes can have up to a 65% lifetime risk of developing breast cancer and also have an increased risk of developing ovarian cancer.[14,16,17]

Family history factors that increase the likelihood of a patient having a BRCA1 or BRCA2 mutation are outlined in Table 3. According to the ACS 2007 breast cancer screening guidelines, several risk assessment models can be used to estimate lifetime breast cancer risk (ie, Gail, Claus, and Tyrer-Cusick models) or the likelihood that a BRCA gene mutation is present (ie, BRCAPro and BOADICEA).[4] Although all of these models depend heavily on family history, they also consider a combination of other risk factors (eg, age, reproductive history, previous breast biopsy); thus, an individual woman's risk estimate may vary with different models.[4]

Table 3. Family History Factors Suggestive of an Increased Risk for BRCA1 or BRCA2 Mutations

≥ 2 first- or second-degree relatives with breast or ovarian cancer
Breast cancer occurring in premenopausal women and/or those diagnosed before age 50 years
Cases of male breast cancer
Simultaneous breast and ovarian cancers or 2 primary breast cancers in the same woman or the same family
Two or more types of BRCA1- or BRCA2-related cancers in a single family member
Ashkenazi Jewish ancestry

Genetic counseling should be considered for women who are found to be at increased risk of having a BRCA gene mutation or developing breast cancer. Women who undergo genetic testing and are found to carry BRCA1 or BRCA2 mutations, or who have other high-penetrance genes for familial cancer syndromes, such as PTEN and p53, should have increased surveillance with breast MRI in addition to annual mammography and clinical breast exams. Women who do not have the aforementioned genetic mutations or who choose not to undergo testing but have a strong family history of breast or ovarian cancer and a more than 20% lifetime risk of developing these cancers should also receive adjunct breast screening MRIs.[4]


Exposure to Mantle Field Radiation

Another known risk factor for breast cancer is exposure to mantle field radiation, which is used as a treatment for Hodgkin lymphoma.[18] A study by Tinger and colleagues showed the incidence of breast cancer in this population to be highest for women treated in the 1960s to mid-1970s compared with those treated in the late 1970s to mid-1980s, when radiation protocols were changed to administer lower doses, with the risk dissipating in the latter group after a median follow-up of 13 years.[19] These findings suggest that Hodgkin disease survivors treated with current approaches are unlikely to have a substantially increased risk of breast cancer. Nevertheless, it is thought that these women may derive the same benefit from breast screening MRIs as women with a strong family history due to their higher risk of a secondary breast cancer. The ACS and ACR guidelines include women with Hodgkin disease or a history of mantle field radiation in their high-risk category and recommend breast screening MRIs in these women.[2-4]

Other High-Risk Groups

In 2006, a meta-analysis showed breast density to be an independent risk factor for breast cancer, with women with dense breasts having a 4- to 5-fold increased risk compared with other women.[20] As previously noted, dense tissue may also make it difficult to identify masses on mammography, necessitating further imaging for cancer detection.

Atypical hyperplasia and lobular carcinoma in situ are high-risk lesions found in approximately 10% of benign biopsies.[21] Studies have shown that the lifetime risk of breast cancer in women with these benign lesions is 30% at 25 years of follow-up.[22-24] Although the level of lifetime risk in these women is higher than the current standard needed for breast MRI screening, breast MRI is currently not recommended due to insufficient data.

Women with a personal history of breast cancer are also at high risk of developing a recurrence or a second breast cancer. Annual mammography is recommended after treatment, but increased screening based on the patient's cancer history and tumor characteristics should be considered.
Collaborative Approaches

Screening for breast cancer has been a topic of debate and a source of high anxiety for women. To optimize breast screening MRIs, a collaborative approach among clinicians and radiologists should be undertaken to improve efficiency and reduce patient anxiety, particularly as breast cancer screening becomes more complex with additional imaging. Coordination of visits and imaging on the same day improves efficiency and can lead to decreased expenses and travel time. Also, allowing for increased imaging and additional views, if needed, during the same mammography or MRI appointment can reduce patient anxiety and the need for additional visits.

Because current ACS recommendations for breast MRI screening do not address the timing of MRI in conjunction with mammography, clinicians and radiologists should develop screening protocols in their community for women at high risk for breast cancer. Ideally, these protocols should include breast MRI for patients who have a more than 20% lifetime risk of developing breast cancer. Alternating imaging between MRI and mammography so that patients are screened more frequently may increase the chance of earlier detection of aggressive and lower-stage cancers.