Controversies in Breast MRI

Controversies in Breast MRI

Joseph B. Sutcliffe III, MD, and Pamela M. Otto, MD, FACR

When used for appropriate indications, breast magneticresonance imaging (MRI) is a powerful diagnostic tool.However, breast MRI has its share of controversies. Thesecontroversies can be a source of confusion for the radiol-ogist or referring physician. This paper addresses 4 breastMRI controversies that we frequently encounter at ouruniversity hospital practice: (1) what are the appropriateindications for screening breast MRI? (2) what are theappropriate indications for the use of breast MRI as aproblems-solving modality? (3) how does one interpret MRIimaging features that have substantial overlap betweenbenign and malignant conditions? and (4) what are theappropriate indications for preoperative breast MRI? Illus-trative case examples are provided.

IntroductionIn 2007, Lehman et al. published the results of theAmerican College of Radiology Imaging Network(ACRIN) 6667 trial.1 This trial demonstrated thedetection of mammographically occult contralateralbreast cancers in 3.1% of women recently diagnosedwith breast cancer. This publication was a watershedevent for breast magnetic resonance imaging (MRI).The study was widely publicized in the media2 andgarnered substantial public attention. Around the sametime, the American Cancer Society (ACS) publishedits guidelines for the use of screening breast MRI,3

and this also received substantial medical and mediaattention. The ACRIN 6667 trial results and ACSguidelines provided evidence-based support to expandthe use of breast MRI. Breast MRI was seen,correctly, by radiologists, referring clinicians, and

Curr Probl Diagn Radiol 2013;42:149–163.& 2013 Mosby, Inc. All rights reserved.0363-0188/$36.00 + 0http://dx.doi.org/10.1067/j.cpradiol.2013.03.001

From the Department of Radiology, University of Texas Health ScienceCenter in San Antonio, San Antonio, TX.Reprint requests: Joseph B. Sutcliffe III, MD, Department of Radiology,University of Texas Health Science Center in San Antonio (UTHSCSA),7703 Floyd Curl Dr. San Antonio, TX 78229. E-mail: [email protected].

Curr Probl Diagn Radiol, July/August 2013

patients as a powerful diagnostic tool that was safe,involved no ionizing radiation, and was able to detectbreast cancer with greater sensitivity than mammog-raphy and ultrasound. The limited specificityand drawbacks of breast MRI were not as wellappreciated. Breast MRI was increasingly utilizedfor high-risk screening purposes. Unfortunately, inreal practice, objective patient risk assessment wasoften lacking and many patients were referred forscreening breast MRI for indications of “strong familyhistory” with limited risk factors provided. Radiolog-ists with different levels of training and experiencewith breast MRI were interpreting breast MRIs anddiscovering the significant overlap between MRIfindings of benign and malignant lesions, particularlywith nonmasslike enhancement (NMLE) and foci.Some radiologists were overutilizing breast MRI as aproblem-solving tool, rather than proceeding directly tostandard stereotactic or ultrasound-guided biopsy oflesions already demonstrated to be suspicious bymammography or ultrasound. The success of preoper-ative breast MRI in detecting mammographically occultmultifocal, multicentric, and contralateral diseaseresulted in more extensive surgeries in many patients.This resulted in a counterargument from many in thesurgical oncology and radiation oncology communitieswho reported that the more extensive surgeries resultingfrom additional breast MRI findings did not translateinto improved surgical outcomes or survival.4-6

All of these issues have substantially muddied thewaters of breast MRI. The following 4 breast MRIcontroversies are the most frequent subjects of debate inour own university hospital-based practice: (1) what arethe appropriate indications for screening breast MRI?(2) what are the appropriate indications for the use ofbreast MRI as a problem-solving modality? (3) how doesone interpret MRI imaging features with substantialoverlap between benign and malignant conditions? and(4) what are the appropriate indications for preoperativebreast MRI? This paper addresses these controversies andprovides a literature review to navigate these questions.

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mailto:[email protected]

First Controversy: What are theAppropriate Indications for ScreeningBreast MRI?After the ACS published its Screening Breast MRIguidelines in 2007,3 there was a substantial increase inpatient interest and clinician referrals for screeningbreast MRIs for patients considered at high risk forbreast cancer. At face value, this should not be acontroversial issue. The guidelines by the AmericanCollege of Radiology (ACR),7 ACS,3 Society ofBreast Imaging (SBI)8 and the National Comprehen-sive Cancer Network (NCCN)9 are, in general, con-sistent with each other regarding the indications. Allof these guidelines recommend annual screening ofbreast MRI (in addition to annual screening mammog-raphy) in women with a greater than 20% lifetime riskof developing breast cancer or one of several geneticsyndromes (eg BRCA1 or BRCA2), or a prior historyof mantle irradiation to the chest during youth. Therisk assessment must be based on objective personalor family history risk factors.So, what is the controversy? In our practice,

patients who are definite candidates for annual screen-ing MRI, such as patients with BRCA1 or BRCA2 orpatients with lifetime risk greater than 20% of devel-oping breast cancer based on objective risk assessment(eg formal genetic consultation), are relatively

FIG 1. A 58-year-old female with greater than 20% lifetime risk of developihistory risk factors receives her annual screening MRI in addition to annual sa true-positive screening MRI finding. (A) T1-weighted postgadolinium corupper outer right breast, posterior depth, from the 9-o-clock to 1-o-clock axisyear's screening breast MRI. Mammographic appearance of this region wasof ill-defined hypoechoic abnormal echotexture at the 9-o-clock axis. Imageabnormal echotexure (arrows) and biopsy needle (arrowheads). Histopath

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infrequent referrals. There really is no controversyfor these patients. If one of these criteria is met, thepatient is a candidate for annual screening MRI as anadjunct to annual screening mammography. The goalof screening MRI in these patients is then to detectmammographically or clinically occult breast cancersat an early stage. The sensitivity of breast MRI is usedas a complementary screening modality in addition toannual screening mammography and as an appropriateclinical surveillance (Fig 1).More frequently, in our practice, we receive refer-

rals for screening MRIs with a vague “strong familyhistory” provided as an indication. Often, no objectiverisk assessment is provided. The actual family historymay range anywhere from history of breast cancer indistant aunts or cousins to truly significant familyhistory of early breast cancer or gynecologic cancer infirst-degree relatives. The patient may already beconvinced of the absolute necessity of having ascreening MRI based on inaccurate risk assessmentby the referring clinician. The patient or referringclinician may have minimal understanding of thelimited specificity of breast MRI and the high like-lihood of false-positive MRI findings leading to addi-tional biopsies (with attendant cost and anxiety)(Fig 2) which would otherwise be avoided. Respectfulattempts by the radiologist to inform the referring

ng breast cancer based on objective assessment of personal and familycreening mammography and clinical surveillance. This is an example ofonal subtraction image demonstrates regional, clumped, NMLE in thepositions (arrows). This was a new finding compared with the previousunremarkable. (B) Targeted second-look ultrasound identified a regionfrom ultrasound-guided core needle biopsy demonstrates the region ofology yielded invasive ductal carcinoma.


FIG 2. A 22-year-old female with greater than 20% lifetime risk of developing breast cancer based on objective assessment of personal and familyhistory risk factors receiving her baseline screening breast MRI. This is an example of a false-positive MRI finding leading to biopsy. (A) T1-weightedpostgadolinium axial subtraction image demonstrates a mammographically occult 0.6-cm oval, enhancing mass in the left lower breast, 6-o-clockaxis, middle depth (arrow). (B) Targeted second-look ultrasound identified the 0.6-cm left breast mass. Image from ultrasound-guided core needlebiopsy demonstrates the mass (arrow) and biopsy needle (arrowheads). Histopathology yielded fibroadenoma, which was concordant with the MRIand ultrasound imaging appearance.

clinician of the drawbacks of screening breast MRIwithout appropriate indication often fail to convince.The radiologist is placed in the uncomfortable role ofappearing as a roadblock to the access of a vitalscreening tool.So, what constitutes a significant family history of

breast cancer? The NCCN guidelines, which areexpert consensus guidelines followed by most surgi-cal, medical, and radiation oncologists, provide anobjective list of family or personal risk factors that areassociated with higher personal risk for breast cancer.9

These include the following: early age of onset ofbreast cancer (o50), 2 breast cancer primaries in asingle individual or 2 or more breast primariesdiagnosed from the same side of the family; breastand ovarian/fallopian tube, or primary peritonealcancer in a single individual or from the same sideof the family; a combination of breast cancer and oneother cancer such as thyroid or endometrial cancer;having a family member with a proven breast cancersusceptibility gene; male breast cancer; or simply ahistory of ovarian, fallopian tube, or primary perito-neal cancer. However, it is important to note that theNCCN specifically recommends referral to a cancergenetics professional for further evaluation if any ofthese risk factors are present. If a patient has ques-tionable indications for screening MRI based onpersonal or family history risk factors, the best courseof action (in the authors' opinion) is to return the issueback to the referring physician, provide the referringphysician with the web-link to the NCCN guide-lines,10 and recommend referral of the patient for aformal risk assessment by someone such as a cancergenetics counselor. If the patient is then objectively


assessed to have a greater than 20% lifetime risk ofdeveloping breast cancer, the patient is a definitecandidate for annual screening MRI in additional toannual screening mammography and appropriate clin-ical surveillance. The recommendation for a formalrisk assessment should not be seen as a blockingmaneuver to avoid an inappropriate referral. Rather, itis the most appropriate first step in the evaluation of apatient who is suspected of having an elevated risk ofbreast cancer based on personal or family history. Thegenetics counselor can objectively assess the patient'srisk factors, determine if genetics testing is indicated,and educate the patient regarding comprehensivebreast cancer risk reduction strategies, which mayinclude annual screening MRI. The patient is betterserved with this approach. Patients who are assessedas not at high risk are then spared the cost, incon-venience, additional biopsies, and anxieties associatedwith an annual screening breast MRI.A scenario that we also occasionally encounter is

whether a patient who has been recently diagnosed withatypical ductal hyperplasia (ADH), lobular carcinomain situ (LCIS), or atypical lobular hyperplasia (ALH)should begin annual screening breast MRI. The medicalliterature places these patients at multifold increasedrelative lifetime risk of developing breast cancer. Shouldannual screening breast MRI be recommended for eachof these patients? The ACS, NCCN, ACR, and SBIguidelines specifically place these patients in the categoryof patients with a 15%-20% lifetime risk of developingbreast cancer and state there is “insufficient evidence torecommend for or against MRI screening.”3,7,8

There is a relative paucity of literature evaluatingthe utility of screening breast MRIs in patients with

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ADH, LCIS, or ALH. A retrospective review byFriedlander et al of 134 patients receiving screeningbreast MRI for a history of LCIS demonstrated amammographically occult breast cancer detection rateof 3.8%, which compared favorably with the 3%cancer detection rate per MRI for patients with aBRCA mutation.11 A 2008 survey of radiologypractices by Basset et al showed that 61% of radiologypractices in the United States included ADH, LCIS,and ALH in their individual practice indications forperforming screening MRIs.12 The official recommen-dation of the SBI and ACR regarding screening breastMRIs for ADH or lobular neoplasia published in ajoint article in 2010 summarized that whether womenwho have a 15%-20% lifetime risk for developingbreast cancer, such as those with biopsy-provenlobular neoplasia, ADH, or prior breast cancer, shouldbe screened with MRI was still in question. Therecommendation was that it may be best for anindividual breast imaging facility to decide on theuse of screening MRI, after consultation with referringclinicians.8 It is the authors' opinion that this is asound recommendation and the decision to obtainscreening MRIs on patients with a history of ADH,LCIS, or ALH should be made on an individual basisafter consultation with the referring clinician and afterassessing other potential risk factors such as familyhistory. Candidates for screening MRI should then bethoroughly educated in regards to increased frequencyof biopsies and false-positives MRI findings so thatthe patient can make a truly informed decision basedon the risk-benefit ratio of beginning screeningbreast MRIs.

Second Controversy: What are theAppropriate Indications for use of BreastMRI as a Problem-Solving Tool?The ACR Practice Guideline for the Performance ofContrast-Enhanced MRI of the Breast7 includes “addi-tional evaluation of clinical or imaging findings” asone of the indications for performing breast MRI. Theguideline specifically states that “breast MRI may beindicated when other imaging examinations, such asultrasound and mammography, and physical exami-nation are inconclusive for the presence of breastcancer, and biopsy could not be performed.” Theguideline goes on to caution, however, that “MRIshould not supplant careful problem-solving mammo-graphic views or ultrasound in the diagnostic setting”

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and “should not be used in lieu of biopsy of amammographically, clinically, and sonographicallysuspicious finding.”7 In our university hospital prac-tice, we occasionally receive requests for breast MRIsfor evaluation of a symptomatic breast complaintbefore a standard diagnostic mammographic andsonographic workup has been performed. In thosecases, we recommend to the referring clinician that theevaluation should begin with a standard diagnosticmammographic or sonographic workup or both. Thisis generally well received by the referring clinician,and the standard diagnostic evaluation answers theclinical question in most cases without the need forbreast MRI. We recommend breast MRI only if amammographic and sonographic evaluation fails toresolve the clinical question. We also occasionallyreceive consultations for further evaluation of patientswho have already received a breast MRI at an outsideinstitution for evaluation of a suspicious mammo-graphic or sonographic finding that has not yet beenbiopsied. In the review of these cases, it is often clearthat the mammographic or sonographic findingsclearly warranted a stereotactic or sonographicallyguided core biopsy and the MRI was an unnecessarytest that added no additional value to the workup. Ouranecdotal experience is that this often occurs in thesetting of a complex cystic mass. Instead of perform-ing an ultrasound-guided core biopsy of the mostsuspicious component of the cystic lesion (eg muralnodule), the radiologist may instead order a breastMRI with the expectation that the MRI would helpdetermine if the lesion is “truly” suspicious. In thesecases, breast MRI rarely adds value to the diagnosticworkup but rather adds cost, delay, and patient anxietyto the equation. In such cases, we strongly agree withthe ACR that MRI should not be used instead of corebiopsy for a mammographically, clinically, or sono-graphically suspicious finding (Fig 3).So, in what situations is problem-solving MRI

indicated? Moy et al provide an excellent review ofthis topic.13 The study was a retrospective review of115 high-risk patients referred for breast MRI forinconclusive mammographic evaluation. In this study,indications for problem-solving breast MRI fell into3 main categories: asymmetries, architectural distortion,and change at the site of a previous benign biopsy. BreastMRI detected breast cancer in 6 of the 115 cases and ofthose 6 cases, 3 were one-view asymmetries, 2 were2-view focal asymmetries, and one was one-view archi-tectural distortion. Only 2 of the 6 lesions were identified


FIG 3. A 75-year-old female referred for newly palpable right breast mass. This is an example of a case for which breast MRI is not required forproblem solving. (A) CC (top image) and MLO (bottom image) digital mammograms demonstrate a large, round, dense circumscribed mass in theright, lower inner breast, which corresponds to the palpable finding. (B) Targeted ultrasound of the mass demonstrates that that mass ispredominately anechoic and cystic; however, there is a prominent mural nodule (marked by measurement calipers) arising from the deep wall of thecystic mass. Is an MRI needed for problem solving? No. Although the mass is predominately cystic, it is new and the presence of a solid muralnodule confirms this as a suspicious lesion. Breast MRI would not likely add additional information in regards to whether or not this lesion should bebiopsied. The nodular component of this lesion was biopsied using ultrasound guidance, yielding a diagnosis of invasive ductal carcinoma.

by targeted “second-look” ultrasound. The authors con-cluded that problem-solving MRI was most useful forasymmetries or one-view architectural distortion withoutsonographic correlate. In our experience, subtle breastfindings can usually be adequately assessed with standarddiagnostic mammographic views and thorough targetedbreast ultrasound. For example, if a 2-view, developing,subtle focal asymmetry persists on spot compressionviews, and there is no sonographic correlate, stereotacticbiopsy or needle localized surgical excision can usuallybe performed rather than ordering an MRI for problemsolving. We agree with the Moy et al that problem-solving MRI has a definite role in a one-view developingasymmetry or one-view developing region of architec-tural distortion without sonographic correlate. We wouldalso add suspicious nipple discharge without mammo-graphic, galactographic, or sonographic correlate asan indication for problem-solving MRI. MRI mayalso be useful for further assessment of questionable


radiology–pathology concordance after stereotactic orsonographic core biopsy (Fig 4). For almost all otherbreast findings, a standard mammographic and sono-graphic examination would answer the question ofwhether a subtle finding represents a true lesion orsummation shadows of normal breast tissue. Most subtlemasses, developing focal asymmetries, complex cysticlesions, and indeterminate microcalcifications do notrequire breast MRI for further assessment. Bottom line:MRI should not be used as a problem-solving tool if theonly function of the examination is to kick the can downthe road.A well-known indication for breast MRI as a

problem-solving tool is further imaging assessment ofthe patient with biopsy-proven metastatic adenocarci-noma in an axillary lymph node with unknown primary.A mammographically occult breast primary cancer isoften the underlying etiology. If standard mammo-graphic and sonographic diagnostic assessment fails to

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FIG 4. A 26-year-old female presented with new eczematous changes of her left nipple with dermal biopsy confirming Paget disease of the breast.This is an example of use of MRI for problem solving. (A) Diagnostic mammogram (CC view) demonstrates a small cluster of fine, pleomorphicmicrocalcifications in the left lateral breast, 3-o-clock axis (small oval) and a regional grouping of course, heterogeneous microcalcificationsspanning the 10-o-clock to 11-o-clock axes (large oval). Both groups of microcalcifications were considered suspicious and were stereotacticallybiopsied. Histopathology of the 3-o-clock axis microcalcifications was ductal carcinoma in situ (DCIS). Histopathology of the 10 to 11-o-clock axesmicrocalcifications was benign stromal fibrosis, with questionable concordance. (B) Problem-solving preoperative MRI (postcontrast 3-D MIP image)demonstrates suspicious NMLE at the 3-o-clock axis biopsy site (arrow), consistent with DCIS diagnosis. There is no abnormal enhancement at the10-o-clock to 11-o-clock axis region (oval), which helped to confirm concordance with the benign biopsy results. The patient was a candidate forbreast conservation therapy with lumpectomy of the DCIS and excision of the nipple-areola complex. This was important information to aid surgicalplanning in this case.

reveal a suspicious breast parenchymal lesion, then MRIshould be the next imaging step. In these cases, MRIwould often yield a mammographically occult suspiciouslesion, particularly in a patient with heterogeneouslydense or extremely dense fibroglandular tissue. Asecond-look ultrasound of that specific location of thebreast would then often reveal a sonographically visiblelesion which can be then be core biopsied with ultra-sound guidance (Fig 5). If the lesion seen on MRI isboth mammographically and sonographically occult,then an MRI biopsy should be performed.

Third Controversy: How does one Interpretand Manage the Overlap BetweenImaging Features of Benign and MalignantConditions?As breast MRI utilization increased, the excellent sensi-tivity of breast MRI for detection of mammographicallyoccult disease became clinically apparent, but the limitedspecificity of breast MRI also became a problem forindividuals who perform breast imaging. Sardenelliet al14 demonstrated that breast MRI had a sensitivityof 94% for detection of breast cancer in a high-riskscreening population. This was substantially better thanmammography (59%) and breast ultrasound (65%) in thesame study. However, breast MRI had a positivepredictive value (PPV) of only 18%-63% in the study,which was lower than mammography (77%) and breastultrasound (65%).

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Breast MRI has a higher specificity for a mass lesion.Guitierrez et al15 demonstrated a PPV of 68% inmasses greater than 1 cm in size with irregular marginsand heterogeneous enhancement. PPV decreases withsmaller mass size, less irregularity of the mass margin,and decreased suspiciousness of enhancement features.Masses seen on MRI are easier to correlate withmammographic and sonographic findings and long-term mammographic or sonographic stability of a mass(eg fibroadenoma), which is incidentally seen on breastMRI, usually confirms its benignity without need forbiopsy. By avoiding biopsy of lesions that are probablefibroadenomas (mammographically stable mass withMRI findings of oval shape, smooth margins, non-enhancing internal septa, T2-weighted hyperintensity,and persistent enhancement curve),16 the PPV of biopsyfor masses identified by MRI can be increased. How-ever, if a mass identified on MRI cannot be confidentlydemonstrated to be a benign mass based on thesecriteria, then, in most cases, the mass should beconsidered suspicious and biopsied. Invasive breastcancers can demonstrate features suggestive of benig-nity on breast MRI (Fig 6). New or enlarging, enhanc-ing masses seen on MRI should always be consideredsuspicious, regardless of features suggestive of benig-nity, such as oval shape, smooth margins, and persistentenhancement curve.The PPV of breast MRI is much lower for NMLE

and often presents a substantial diagnostic dilemmafor the radiologist. There is significant overlap between


FIG 5. A 49-year-old female referred for palpable left axillary masses. This is an example of use of MRI for problem solving. (A) Diagnosticmammogram (partial MLO view) demonstrates bulky left axillary lymphadenopathy (arrow). The breast parenchyma is heterogeneously dense. Noother mammographic lesion is identified. (B) Ultrasound-guided core biopsy of the largest node (arrow) was performed (arrowhead demonstratescore biopsy needle). Histopathology yielded metastatic mammary carcinoma. (C) Review of initial diagnostic mammograms failed to reveal anindex lesion. Breast MRI was performed to detect a mammographically occult primary tumor. Sagittal postcontrast T1-weighted subtractionparametric color image demonstrates a heterogeneously enhancing 1.6-cm mass at the 4-o-clock axis of the left breast (arrow) and bulky left axillarylymphadenopathy (arrowhead.) (D) Targeted second-look ultrasound identifies the mammographically occult 1.6-cm left breast mass (marked bymeasurement calipers). Ultrasound-guided core biopsy was performed yielding invasive ductal carcinoma. (E) Postbiopsy mammogram (MLO view)demonstrates biopsy clip (arrow) at the location of the mammographically occult mass. (Color version of the figure is available online.)

the MRI imaging features of benign and malignantconditions which present with NMLE. NMLE canrepresent physiological enhancement, fibrocystic changes,other benign conditions, DCIS, or invasive cancer(Fig 7). NMLE lesions have been demonstrated to bethe major cause of false-positive breast MRI findings.17

Gutierrez et al15 demonstrated a PPV of only 4% forNMLE less than 1 cm in size. The highest PPVassociated with NMLE in that study was a PPV of4%-24% for NMLE greater than 1 cm in size withclumped, reticular, or dendritic morphology. Multiplefactors should be taken into account when assessingNMLE. If the MRI has been performed for preoperativepurposes in a patient with a known breast cancer, theindex of suspicion for any asymmetric NMLE should berelatively high. Mammographic or sonographic correlateshould be sought and if a benign etiology cannot bedetermined by imaging, then biopsy vs short-intervalMRI follow-up should be strongly considered. The sameapproach applies for NMLE discovered as an incidentalfinding on a screening MRI in a high-risk patient.When NMLE is discovered as an incidental

finding, the first step should be mammographic and


sonographic correlation, which may help to confirmif the finding is suspicious or benign. For example, ifultrasound demonstrates benign cysts in the regionof the NMLE, it most likely represents fibrocysticchange. The same holds true if the NMLE correlatesto a region of milk of calcium–type calcificationsseen mammographically. By the same token, ifmammographic correlation demonstrates microcalci-fications that cannot be confidently assessed asbenign then stereotactic biopsy should be stronglyconsidered. If second-look ultrasound demonstratesany suspicious finding in the region, it should bebiopsied. In our experience, NMLE that representscancer, often correlates sonographically as focal, ill-defined, hypoechoic, disturbed echotexture whichrepresents a high-yield target for sonographicbiopsy.In a situation where NMLE is incidentally discovered

and there is no mammographic or sonographic correlateand the patient is not a preoperative patient with knownbreast cancer or a high-risk patient, then the decision tobiopsy or follow or assess as benign should be based onthe overall distribution, asymmetry, morphology, and

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FIG 6. A 42-year-old female with undergoing screening breast MRI for high-risk indication. This is an example of a breast cancer demonstratingMRI features typically associated with benign lesions. (A) Coronal T1 postcontrast parametric color image (non–fat-saturated, nonsubtracted)demonstrates a 6-mm oval, smooth margined mass at the 3-o-clock axis of the left breast (arrow). (B) Enhancement curve of the mass ishomogeneous, type 1, progressive enhancement. The mass was localized and biopsied by second-look ultrasound, yielding histopathology ofinvasive ductal carcinoma. (Color version of the figure is available online.)

enhancement characteristics of the NMLE. Based on theGutierrez et al findings,15 MRI-guided biopsy should bestrongly considered for NMLE greater than 1 cm withclumped, reticular, or dendritic morphology. In most cases,a Breast Imaging Reporting and Data System (BI-RADS)3, probably benign assessment, with short-interval MRIfollow-up, represents a safe approach to regions of NMLEthat do not meet these size or morphology criteria. Thereare also many cases where NMLE simply representsphysiologic enhancement in asymmetric normal fibro-glandular tissue and, with experience, it is reasonable fora radiologist to assess these as benign if the NMLE isconcordant with a benign mammographic or sonographicappearance or both. As with all breast MRI findings in the

FIG 7. Examples of similar NMLE in 2 different patients with different undeappearance between benign and malignant breast conditions. (A) Patientpostcontrast T1-weighted subtraction image demonstrates focal low signal inof recent stereotactic biopsy-proven DCIS. Clumped, linear NMLE extendsregion was biopsied under MRI guidance yielding histopathology of fibrocybreast MRI with known diagnosis of invasive ductal carcinoma of the left breimage demonstrates curvilinear, segmental, clumped NMLE at the 8-o-clocklook ultrasound identifies a corresponding region of disturbed echotextuinvasive ductal carcinoma.

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preoperative setting, surgical decisions should not beperformed based only on the imaging appearance withoutthe recommendation of an imaging-guided biopsy beforedefinitive surgical decisions.Another diagnostic dilemma in breast MRI is the

assessment and management of foci. A focus is asmall spot of enhancement, less than 5 mm in size,which is so small that it is unclear whether or not itrepresents a mass. Foci are also affectionately referredto as “UBOs” (unidentified bright objects) by someradiologists. In general, the risk that a focus representscancer is very low, demonstrated to be less than 3% ina study by Liberman et al in 2006.18 However, fociwould rarely represent tiny cancers, so foci cannot be

rlying histopathologies. These are examples of overlap of MRI imagingA: A 59-year-old female receiving preoperative breast MRI. Coronaltensity at location of clip imbedded in collagen plug (arrowhead) at siteinferiorly into the lower outer quadrant of the left breast (arrow). Thisstic changes. (B) Patient B: A 63-year-old female receiving preoperativeast (index tumor not shown). Axial postcontrast T1-weighted subtractionaxis region of the right breast (contralateral breast) (arrows). Second-re, which was sonographically biopsied, yielding histopathology of


FIG 8. A 46-year-old female receiving screening breast MRI for high-risk indication. This is an example of a focus enlarging in size over time withbiopsy yielding breast malignancy. (A) Axial postcontrast T1-weighted subtraction image demonstrates a 4-mm enhancing focus in the right breast9-o-clock axis. (B) Enhancement curve of the focus is type III, washout. The lesion was assessed as probably benign, BI-RADS-3, with 6-month MRIfollow-up recommended. (C) 6-month follow-up MRI: axial postcontrast T1-weighted subtraction image demonstrates interval enlargement of thefocus, which has developed into a 9-mm enhancing mass. The mass was identified and biopsied by second-look ultrasound, yielding histopathologyof invasive ductal carcinoma. (Color version of the figure is available online.)

simply overlooked. Eby et al,19 provides probably thelargest prospective study of foci, a study that pro-spectively followed 168 foci over a period of severalyear. They assessed the kinetic curve of the eachfocus, which was typically not done in prior studies.They assessed foci with persistent enhancementkinetics as BI-RADS 2 benign, but followed thosefoci by MRI based on the study design, to ensurestability or benignity. No cancers developed in any ofthe foci with persistent curves. They assessed fociwith plateau or washout curves as BI-RADS 3 prob-ably benign and also followed those with surveillanceMRI. Only 2% of the BI-RADS 3 probably benignfoci were ultimately diagnosed as cancers. Theauthors’ conclusion was that enhancement kineticassessment was a useful feature to differentiatedefinitely benign foci from probably benign foci andthat surveillance MRI for foci could be significantlydecreased if foci with persistent curves were assessedas benign at the time of the initial MRI interpretation.We agree that this appears to represent a safe way tomanage foci detected on MRI, with the exception, thatif the foci is detected in a high-risk patient, and is anew finding, regardless of the kinetic enhancementcurve, the foci should be managed with short-intervalMRI follow-up or biopsy. Foci that demonstrateinterval enlargement on subsequent MRIs shoulddefinitely be biopsied (Fig 8).

Fourth Controversy: What are theAppropriate Indications for PreoperativeBreast MRI?Since 2007, there have been numerous publications,mostly retrospective reviews, assessing the effect ofpreoperative MRI on surgical management of patientswith newly diagnosed breast cancer. Most of these


studies demonstrate substantial increases in mastec-tomy rates in patients who were breast conservationsurgery (BCS) candidates before additional MRIfindings.20-27 It is well known that preoperative breastMRI is the most sensitive preoperative imagingassessment tool and often detects mammographicallyand clinically occult multifocal, multicentric, or con-tralateral disease or occult lymphadenopathy (Fig 9).A meta-analysis by Houssami et al23 that included

data from 2610 women who received preoperativeMRIs for newly diagnosed breast cancers demonstratedmammographically occult multifocal or multicentriccancer in the ipsilateral breast in 16% of cases overall,with detection rates in the individual studies rangingfrom 6% to 34%. The ACRIN 6667 trial1 demonstrateddetection of mammographically occult malignancies inthe contralateral breast in 3% of patients with newlydiagnosed breast cancer. The Houssami et al meta-analysis demonstrated a conversion from BCS tomastectomy in 8% of patients, a conversion to widerlocal excision in 11% of patients, and contralateralbreast surgery (often bilateral mastectomy) in an addi-tional 4% of patients, as a result of additional findingson preoperative MRI. The intuitive assumption is thatdetection of mammographically occult disease by MRIand its effect on surgical management would bebeneficial to patient survival.Unfortunately, the peer-reviewed research has pro-

vided a very mixed picture regarding the clinicalbenefit of preoperative MRI. A retrospective Europeanstudy of 432 patients by Fischer et al21 over a follow-up period of approximately 40 months, demonstrated alocal recurrence rate of 6.8% in patients who did notreceive preoperative MRI before BCS compared witha local recurrence rate of only 1.2% in patients whodid receive preoperative breast MRI. However, poten-tial selection bias was a weakness of the study as the

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FIG 9. A 51-year-old female with architectural distortion in the left upper outer breast. This is an example of preoperative breast MRI detectingmammographically occult contralateral disease. (A) Bilateral digital screening mammograms (CC and MLO views) demonstrate a focal region ofarchitectural distortion in the upper outer left breast (circles). Targeted ultrasound (not shown) demonstrated a 3.5-cm spiculated mass at the 3-o-clock axis which was sonographically biopsied, yielding histopathology of invasive ductal carcinoma. (B) Preoperative MRI axial postcontrast T1-weighted parametric color image demonstrates the index tumor in the left breast, 3-o-clock axis (arrow). (C) Same MRI, at slightly caudal level,demonstrates a heterogeneously enhancing, irregularly shaped 3 cm mass in the right breast 8-o-clock axis region. The mass demonstrated a typeIII, washout, enhancement curve. This mass was mammographically and clinically occult. Second-look ultrasound identified the mass and ultrasound-guided core biopsy yielded histopathology of invasive ductal carcinoma (contralateral malignancy). (Color version of the figure is available online.)

treatment and control groups were not matched, andthose patients who underwent breast MRI had cancersless advanced compared with the patients who did notreceive preoperative MRI. The British ComparativeEffectiveness of MRI in Breast Cancer multicenter,randomized trial28 demonstrated no benefit of preop-erative MRI toward decreasing the reoperation rate inpatients receiving BCS. This was a larger, randomized

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study with a total of 1623 patients. The study assessedthe reoperation rate, primarily owing to positivemargins, over the 6-month period following initialsurgery. The reoperation rate in both groups wasessentially equivalent at 19%, with preoperative MRIdemonstrating no benefit in decreasing the reoperationrate. Solin et al29 performed a retrospective review of756 women with early stage invasive breast cancer or


ductal carcinoma in situ, 215 of whom received apreoperative breast MRI and 541 had no preoperativebreast MRI. The study demonstrated no statisticallysignificant difference in 8-year local failure rate (3%of patients with preoperative breast MRI and 4%without preoperative breast MRI) or 8-year overallsurvival rate (86% vs 87%). This study was adisappointing result for advocates of preoperativebreast MRI; however, there were weaknesses of thisstudy. It was a nonrandomized, retrospective studyand all women identified as having extensive diseaseby MRI and who received a mastectomy as a resultwere excluded from the results. There was potentialselection bias for patients with clinically moreadvanced disease receiving preoperative breast MRI.Additionally, although no survival advantage wasdemonstrated after 8 years for patients receivingpreoperative breast MRI, the unanswered questionlingers of potential survival advantages at moreprolonged follow-up time intervals.Critics of preoperative MRI acknowledge the sen-

sitivity of MRI for the detection of additional mammo-graphically occult disease but counter that the datashow no clinical benefit of preoperative MRI. Edito-rials with titles such as “MRI in the Breast CancerPatient: Curb Your Enthusiasm”

4 and “More Mastec-tomies: Is This What Patient’s Really Want?”5 capturethe essence of the critical perspective of preoperativebreast MRI. If there is no benefit in outcome, thenwhy should physicians and their patients accept anincrease in mastectomy rates, wider local excisions,expense of treatment, potential delay in treatment, andincreased patient anxiety related to preoperative breastMRI? The critics of preoperative breast MRI point outthat it has already been proven that mammographi-cally occult residual disease can be effectively con-trolled with radiation therapy after BCS. Landmarkprospective clinical studies, the National SurgicalAdjuvant Breast and Bowel Project (NSABP) B-04and B-06 trials, confirmed the effectiveness of radia-tion therapy following BCS. The NSABP B-06 trialspecifically showed equal overall survival for patientstreated with lumpectomy and radiation therapy com-pared with patients who received mastectomy.30 Thecentral question of this dilemma is should we use apowerful diagnostic tool if it does not improve patientsurvival and perhaps harms patients by leading tomore extensive surgery than is needed? Additionalrandomized, prospective studies are needed to defin-itively determine if there is a clinical benefit of breast


MRI in reducing local recurrence rates or improvinglong-term survival rates.In light of the controversies surrounding preoper-

ative breast MRI, it is difficult to develop evidence-based indications for it. Although outcome datais lacking, there are potential subsets of patientswho might benefit more from preoperative MRI.31,32

These include patients with newly diagnosed invasivelobular breast cancers, BRCA1 or BRCA2 patientswith newly diagnosed breast cancer, young patientswith newly diagnosed breast cancers, or patients withnewly diagnosed breast cancer with mammographi-cally dense fibroglandular tissue. Additionally, signifi-cant mammographic and sonographic size discrepancyof the index breast tumor, clinical concern for exten-sion to chest wall structures, or large tumors thatmay be candidates for neoadjuvant (preoperative)chemotherapy are other indications for which preop-erative breast MRI can answer clinically relevantquestions.Invasive lobular carcinoma (ILC) often grows in an

infiltrative manner which is mammographically subtle.Mammography often underestimates the extent ofdisease with ILC. ILC is a subset of breast cancerfor which preoperative MRI has shown substantialeffectiveness in the detection of mammographicallyoccult extent of disease.33,34 Mann et al22 assessed theinfluence of preoperative breast MRI on the reexcisionrate on patients with newly diagnosed ILC in aretrospective cohort of 267 patients. Of 166 patientswho did not receive preoperative MRI, 27% ofpatients required reexcision after initial BCS primaryowing to positive surgical margins at initial surgery.Of the 99 patients who had preoperative MRI beforeinitial BCS, only 9% required reexcision. Weaknessesof the study included relatively small cohort size,retrospective design, and potential selection bias. Thestudy also did not assess long-term survival benefit ofpreoperative MRI. However, the reduction in reexci-sion rates for positive surgical margins was statisti-cally and clinically significant. Recent retrospectivestudies of the utility of preoperative breast MRI inpatients newly diagnosed with ILC by Heil et al20,35

demonstrated an increased primary mastectomy rateand bilateral surgery rate without a decreased reopera-tion rate. Overall, preoperative MRI demonstratesadditional ipsilateral disease in 32% in patients withnewly diagnosed ILC and mammographically andclinically occult contralateral breast cancer in 7% ofthese patients.33 Of note, the 7% contralateral breast

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cancer MRI detection rate in ILC patients is higherthan the 3% contralateral MRI detection rate for allsubtypes of breast cancer shown in the ACRIN 6667trial1 (Fig 10).MRI has been shown to be much more sensitive

than mammography for the assessment of extent ofdisease in patients with heterogeneously dense ordense breast tissue. A prospective nonrandomized trialinvolving preoperative imaging assessment for pati-ents with biopsy-proven breast cancer by Sardenelliet al36 demonstrated sensitivity of MRI of 81% for thedetection of multifocal or multicentric breast diseasewith a PPV of 71% in patients with scatteredfibroglandular density, heterogeneously dense, ordense breast tissue undergoing preoperative assess-ment compared with a mammographic sensitivityranging of 60% and PPV of 78% for the same pati-ents. In another study comparing preoperative MRIwith mammography and ultrasound in patients withdense breast tissue, Goethem et al37 demonstrated thatmammography underestimated extent of disease in37%, ultrasound in 40%, and MRI in only 12.5%. Inthat study, of the patients with multifocal or multi-centric carcinoma, mammography detected the lesionsin 35%, ultrasound in 30%, and MR in 100%, with afalse-positive rate of 12.5, 14, and 23% respectively(Fig 11).

FIG 10. A 58-year-old female referred for a palpable lump in the left umammographically and clinically occult multicentric disease in a patient wviews) demonstrate an indistinct 2-cm mass with associated architectural disshown) identified the mass. The mass was sonographically biopsied yieldingorientation) demonstrates the index tumor (arrow) but additionally identifies naxis of the left breast. These mass were mammographically and clinically ocdeclined and opted for a modified radical mastectomy. Final surgical path

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SummaryThe strength of breast MRI is its greater sensitivitycompared with mammography and breast ultrasound.The primary weaknesses of breast MRI are its limitedspecificity and cost. As a result, controversies surround theappropriate indications for the use of breast MRI. We haveoutlined common controversies about breast MRI that weencounter in our university hospital practice setting. BreastMRI is the most sensitive screening modality for patientswho have a high lifetime risk for developing breast cancer.Unfortunately, screening breast MRI results in many false-positive findings that result in additional biopsies, patientanxiety, and increased cost of care. Clearly defining whichpatients are in the high-risk category and for whom thebenefit of screening breast MRI outweighs the risk offalse-positive findings and increased cost of care isextremely important. For patients with lifetime risk ofdeveloping breast cancer greater than 20%, based onobjective risk assessment, annual screening breast MRI inaddition to annual screening mammography is indicated.Unfortunately, many patients fall into 15%-20% lifetimerisk category, such as patients with biopsy-proven LCIS,ADH, or ALH or with milder personal or family riskfactors. There is no strong empiric evidence of benefit orlack of benefit of screening breast MRI for these patients.For this reason, the ACR and SBI jointly recommend thatindividual breast imaging facilities should decide which

pper outer breast. This is an example of breast MRI demonstratingith ILC. (A) Bilateral digital diagnostic mammograms (CC and MLO

tortion in the left breast 2-o-clock axis (circles). Targeted ultrasound (notILC. (B) Preoperative breast MRI (postcontrast 3-D MIP image, sagittalumerous smaller enhancing masses extending inferiorly to the 6-o-clockcult. Second-look ultrasound biopsy was recommended, but the patientology confirmed multicentric ILC extending into the inferior left breast.


FIG 11. A 47-year-old female with recent diagnosis of DCIS in the 2-o-clock axis of the left breast. This is an example of preoperative MRIdemonstrating mammographically and clinically occult disease in a patient with heterogeneously dense breast tissue. (Images courtesy N. CarolDornbluth, MD, University of Texas Health Science Center San Antonio.) (A) Diagnostic digital mammograms (right MLO and left ML views)demonstrate a cluster of suspicious microcalcifications in the upper outer left breast (circle) in a patient with heterogeneously dense breast tissue.(B) Enlarged view of the cluster of suspicious microcalcifications in the left upper outer breast. These were stereotactically biopsied yieldinghistopathology of DCIS. (C) Preoperative MRI axial postcontrast T1-weighted subtracted parametric color image demonstrates a heterogeneouslyenhancing mass in the right breast 7-o-clock axis region (arrow). Second-look ultrasound identified the mass, which was sonographically biopsied,yielding histopathology of invasive ductal carcinoma. This contralateral mass was mammographically and clinically occult. Incidentally, an oval,minimally enhancing mass with MRI characteristics consistent with a fibroadenoma was identified in the left medial breast (oval). (Color version ofthe figure is available online.)

patients in this category should be recommended forscreening MRI after consultation with the referringphysician. Also, formal consultation by a genetics counse-lor should always be considered when elevated lifetimerisk of breast cancer is clinically suspected.Breast MRI is often used as a problem-solving tool.

Unfortunately, breast MRI can be used unnecessarilywhen diagnostic mammography, ultrasound, or standardstereotactic or sonographic core biopsy should be per-formed instead. The ACR firmly recommends that MRIshould not be used as problem-solving tool to replace athorough mammographic or sonographic workup or bothand should not be used in lieu of percutaneous biopsy ofa lesion already demonstrated to have suspicious mam-mographic or sonographic features. Appropriate indica-tions for problem-solving breast MRI include furtherassessment of mammographically visible asymmetries orarchitectural distortion, without sonographic correlate,


mammographically visible changes at the site of a priorbenign biopsy,13 and potentially for suspicious nippledischarge, if mammographic, sonographic, or galacto-graphic assessment is inconclusive.The overlap of imaging features between benign and

malignant conditions is another commonly encounteredpractical dilemma for the radiologist interpreting breastMRIs. NMLE is a common finding with substantialoverlap between benign and malignant conditions.Fortunately, there is some empiric evidence that NMLEgreater than 1 cm in size with clumped, reticular, ordendritic morphology demonstrates a much higher PPVthan NMLE less than 1 cm in size. Also, there is someevidence that foci, which are frequently seen on MRI,can be assessed as benign if they demonstrate persistentenhancement curves and can be assessed as probablybenign and closely followed if they demonstrate plateauor washout curves.

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Finally, the most controversial current topic regardingbreast MRI is determining appropriate indications forpreoperative breast MRI. There is substantial evidencethat breast MRI is the most sensitive imaging modalityfor assessment of the local extent of disease andspecifically for the detection of mammographically andclinically occult multifocal, multicentric, or contralateraldisease. Our anecdotal experience is that there is a widevariation of acceptance and utilization of preoperativeMRI from radiologist to radiologist, surgeon to surgeon,and institution to institution. Many radiologists and breastsurgeons embrace MRI with the belief that by providinga more accurate preoperative imaging assessment, surgi-cal excisions are more likely to remove all macroscopicdisease and ultimately result in long-term clinical benefitfor the patient. Unfortunately, there has been no objectiveevidence of clinical benefit for the patient in increasedsurvival. For this reason, there are many who advocate avery limited role of breast MRI in preoperative imagingassessment. The primary argument against preoperativebreast MRI is that it leads to higher mastectomy rates andwider local excisions for residual disease that could havebeen effectively controlled by standard BCS and radia-tion therapy.There may be subsets of patients with newly

diagnosed breast cancer who might potentially benefitfrom preoperative MRI, though empiric evidence isstill lacking. These include patients with newly diag-nosed breast cancers in the following categories: ILC,BRCA1 and BRCA2 patients, patients with densebreast parenchyma, very young patients, patients withsignificant mammographic and sonographic size dis-crepancies of the index tumor, patients for whom chestwall invasion is clinically suspected, or patients withlarge tumors who would be receiving neoadjuvant(preoperative) chemotherapy. There is a need for welldesigned and adequately powered prospective studiesto determine if any of these subsets of patients benefitfrom preoperative MRI in regards to decreased localrecurrence rates or improved overall survival rates.

Acknowledgments: The authors would like tothank N. Carol Dornbluth, MD for contribution ofcase for Fig 11.

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Controversies in Breast MRI