brca1 and brca2 are the most well known gene mutations responsible for an increased risk for developing breast cancer . a brca1 or brca2 mutation carrier ( brca - mc ) has approximately a 3% risk of getting breast cancer before the age of 30 . this risk increases to almost 50% when she reaches the age of 50 and becomes 5080% at the age of 70 [ 1 , 2 ] . to reduce this risk , these women can choose between bilateral prophylactic mastectomy , oophorectomy   or chemoprevention . in breast cancer , close surveillance contributes to a more favorable stage of disease at detection and may reduce the rate of death from breast cancer [ 6 , 7 ] . in the surveillance or general screening for breast cancer , however , due to the young age and thus in most cases dense breast tissue , the sensitivity for mammography is moderate . false - negative rates of up to 62% have been reported for mammography in screening gene mutation carriers [ 8 , 9 ] . a malignant lesion in the breast is mammographically best detected if it presents itself as an ill - defined or spiculated mass , a group of microcalcifications or as an architectural distortion . a smoothly outlined well - defined mass detected on mammography has a chance of less than 1% of being malignant [ 10 , 11 ] . kaas et al . [ 13 , 14 ] have evaluated the mammographic appearance of breast cancer in brca - mc . tilanus and coworkers found the mammographic appearance suspicious for a malignancy in only 38% of the gene carriers in comparison with 71% in a control group .  prominent pushing margins  caused by a continuous front of tumor cells not separated by connective tissue were described in the brca - mc group as the main reason for a false - negative evaluation of mammograms . kaas and coworkers concluded in their study of 31 breast cancer cases in brca - mcs that all mammographically detected lesions should be further evaluated by ultrasound and biopsy regardless of their appearance . well - defined mammographic tumors correlated in 83% with histologic circumscribed tumor margins in brca1-mcs . for women with an increased risk for developing breast cancer magnetic resonance imaging ( mri ) should be included for close surveillance [ 15 , 16 ] . the superior sensitivity of mri ( 81% ) for the detection of breast cancer in these women compared with mammography ( 40% ) has been proven in literature . however the classification of a lesion detected on mr as benign or malignant still remains a challenge . focal masses with smooth borders are associated with a high negative predictive value for malignancy . an irregular lesion contour , inhomogeneous enhancement pattern and rim enhancement have been reported as features indicating malignancy . the dynamic evaluation is often based on the enhancement characteristics 27  min after the injection of a paramagnetic contrast agent . in this approach , the decrease of signal intensity , often referred to as a type 3 curve or washout , is highly predictive for breast cancer , with a likelihood of malignancy of 87% . until now the appearance of breast malignancies in brca - mcs has only been investigated for mammography . in this study we analyzed the mri characteristics of brca - mc - associated tumors compared with sporadic cases of breast cancer . all available ( 35 ) brca - mcs with a biopsy - proven malignancy , imaged with mri for screening   or pre - operative evaluation in the period from july 2000 until november 2006 , were included in the study : 23 brca1 carriers and 12 brca2 carriers . in order to compare tumor characteristics with sporadic cases of breast cancer an age , tumor type and tumor size matched control group was composed from 206 consecutive sporadic breast cancer cases imaged with mri in the period from november 2001 until january 2007 . all brca - mc cases were age matched within 5  years with sporadic breast cancer cases . cases were also matched for tumor type ( idc , ilc or dcis ) and pathological tumor size . for size matching , the brca - mc cases were matched to the closest tumor size in the sporadic cases available , with a limit for the maximum size difference of 0.5  cm for tumors smaller than 1  cm , 1-cm difference for tumors up to 5  cm and 1.5-cm difference for tumors larger than 5  cm . mammograms were obtained in the mediolateral oblique and craniocaudal direction on a digital mammographic unit ( senograph 2000 d or a senograph ds , ge healthcare , wis . , usa ) . detection , density of the lesion compared with breast tissue , lesion morphology , and size were scored . in the morphologic assessment , lesion type was classified as either a mass , a calcifications or as an architectural distortion . lesion shape was described as rounded , lobulated or irregular and lesion margins as sharp , vague or spiculated . the size of the tumor was measured by determining the longest axis through the displayed lesion . spiculae surrounding a solid lesion were interpreted as desmoplastic reaction and not included in the measurement . mri investigations were performed on a 1.5-tesla system with a double breast coil ( magnetom vision , sonata or symphony , siemens , erlangen , germany ) . in the scanning , we used a coronally orientated three - dimensional fast low - angle shot ( flash 3d ) with the following parameters : te 4  ms , tr 8.1  ms , fa 20 , fov 360  mm , ta 96  s , image resolution 1.5  mm    1.5  mm    1.5  mm for all patients scanned prior to june 2004 and te 4  ms , tr 7.5  ms , fa 8 , fov 320  mm , ta 87  s , image resolution 1.3  mm    1.3  mm    1.3  mm for all patients scanned after june 2004 . all patients were placed in the prone position , with the breasts in the double breast coil and positioned at the isocenter of the magnet . after localizer images were obtained in three directions and a precontrast flash 3d series was recorded , 0.1  mmol / kg bodyweight gadolinium chelate ( magnevist , schering , germany or dotarem , guerbet , the netherlands ) was administered using a power injector ( spectris , medrad , usa ) at 2.5  ml / s followed by a 15-ml saline flush at the same injection rate . all mri examinations were retrospectively evaluated on a dedicated breast mri workstation ( dynacad , invivo , usa ) scoring lesion detection , size , morphology and enhancement kinetics . maximum intensity projections , coronal images and axial reconstructions of both the t1 weighted and subtracted images and time - intensity curves were displayed . the enhancement pattern of a lesion was classified as homogeneous , heterogeneous or rim enhanced . lesion enhancement kinetics were evaluated according to the criteria described by kuhl et al . . type 2 shows a plateau after initial increased enhancement , where the maximum signal intensity is reached approximately 23  min after contrast injection and remains constant . this type of curve is seen in both benign and malignant lesions . in a type 3 curve , the peak enhancement is reached in the early postcontrast phase , and this is followed by a decrease of signal intensity ( wash - out ) . the dynamic curves were evaluated based on a single voxel or by selecting a region of interest within the lesion , the workstation allowed the readers to use both methods . because of the possible bias in this retrospective study , a bi - rads classification   could not be scored objectively and was therefore not included in the evaluation . except from the knowledge of a malignancy being present , the radiologists were blinded to any other clinical information . , the tumor type , size and mitotic activity index ( mai ) were recorded . the study was approved by the institutional review board ; since the study was performed retrospectively , informed consent was not required according to the review board . in the statistical evaluation , differences in patient and tumor characteristics between the brca - mc and control group were analyzed using an independent sample t - test if variables were continuous and normally distributed . for categorical variables , the pearson chi - square test was used and we used fisher s exact test when any of the expected values was less than five . pearson s correlation coefficients were calculated for both mammographic size and mri size versus pathologic size . six brca - mc cases could not be matched according to the criteria defined ; these cases were excluded from the study . four brca - mcs were excluded because no match could be found based on patient s age ; the other two were excluded because no match could be found based on tumor size . the mean age and tumor size of the excluded cases were , respectively , 33  years ( range 2736 , median 35 , sd 3.4  years ) and 1.4  cm ( range 0.62.8  cm , median 1.1  cm , sd 0.8  cm ) . a total of 29 brca - mc cases were included for this study . in the brca - mc group , five women were symptomatic ( 17% ) ; 21 women were symptomatic in the control group ( 83% ) . mean age in the brca - mc group was 42  years ( range 3268  years , median 40  years , sd 8.0  years ) ; this was 44 ( range 3764  years , median 43  years , sd 5.6  years ) for the control group . the mean pathological tumor size was 2.0  cm ( range 0.47.0  cm , median 1.4  cm , sd 1.5  cm ) in the brca - mc group and 2.3  cm ( range 0.67.0  cm , median 1.9  cm , sd 1.7  cm ) in the control group . no significant difference was found for patient age ( p  =  0.289 ) or maximal pathological tumor size ( p  =  0.371 ) . the mean tumor size on mammography was 2.1  cm ( range 0.57.0  cm , median 1.5  cm , sd 1.49  cm ) . the mean tumor size on mri was 2.4  cm ( range 0.67.1  cm , median 1.8  cm , sd 1.75  cm ) . there was a significant correlation between imaging measurements and pathological measurements <  0.001 ) for mri measurements . in both the brca - mc and control groups , 23 cases were based on invasive ductal carcinoma ( idc ) , two cases on invasive lobular carcinoma ( ilc ) , one case on ductal carcinoma in situ grade 1 ( dcis1 ) and three cases on ductal carcinoma in situ grade 2 ( dcis2 ) . in the brca - mc group , a mean mai of 33.0 ( range 6100 , median 27 , sd 27.1 ) was found , compared with 17.5 ( range 160 , median 14 , sd 15.9 ) in the control group . the difference in mai between the brca - mc and control groups was found to be significant ( p  =  0.044 ) . in the control group , therefore , the overall detection is significantly better with mri than with mammography ( p  =  0.021 ) . mammography detected 22 ( 76% ) lesions in the brca - mc group and 22 ( 79% ) in the control group . all lesions missed on mammography in the brca - mc were idc . in the control group , lesions in the brca - mc group were significantly more described as rounded ( 12//19 vs 3/13 , p  =  0.036 ) and were more often described to have sharp margins ( 9/19 vs 1/13 , p  =  0.024 ) . lesions in the control group were significantly more described as irregular ( 10/13 vs 6/19 , p  =  0.029 ) . from the six brca - mcs that were excluded , only three lesions were detected on mammography . in two cases a mass was detected and in one case calcifications . table  1mammographic lesion characteristics for both groups  brca - mc groupcontrol groupp valuelesions detectedn  =  22n  =  22lesion typemass19130.042arch . distortion140.345calcification250.216lesion densityhyperdense810.050isodense11120.050lesion morphologyrounded1230.036lobulated11.000irregular6100.029lesion marginssharp910.024vague880.473spiculated240.194lesion density , morphology and margins of mass - like lesions only mammographic lesion characteristics for both groups lesion density , morphology and margins of mass - like lesions only on mri , 27 lesions ( 93% ) were detected in the brca - mc group , 28 ( 97% ) in the control group . the lesions missed in the brca - mc group were both cases of dcis , one case of dcis1 , seen on mammography as an architectural distortion , and one case on dcis2 , seen on mammography as a mass . the lesion missed in the control group was based on dcis2 , seen on mammography as calcifications . their was no significant difference found for the detection of breast cancer between mammography and mri within the brca - mc ( p  =  0.18 ) or the control group ( p  =  0.13 ) . lesions in the brca - mc group were significantly more often described as rounded ( 16/27 vs 7/28 , p  =  0.010 ) , with sharp margins ( 20/27 vs 7/28 , p  <  0.001 ) and to show rim enhancement ( 7/27 vs 1/28 , p  =  0.025 ) . lesions in the control group were significantly more often described as irregular ( 18/28 vs 8/27 , p  =  0.010 ) , with vague margins ( 15/28 vs 6/27 , p  =  0.017 ) and with a heterogeneous enhancement pattern ( 22/28 vs 12/27 , p  =  0.009 ) . no significant difference between the two groups was found for enhancement kinetics ( p  =  0.667 ) . from the six brca - mcs that were excluded , five were detected on mri . the delineation was described as sharp in four and as vague in one of these cases . the enhancement pattern was described as homogeneous in two , heterogeneous in one and as rim - enhancement in two of these cases . table  2mri lesion characteristics for both groups  brca - mc groupcontrol groupp valuelesions detectedn  =  27n  =  28lesion morphologyrounded1670.010lobulated331.000irregular8180.010lesion marginssharp207<0.001vague6150.017spiculated160.049enhancement patternhomogeneous850.304heterogeneous12220.009rim710.025enhancement kineticstype in this study , the overall false - negative rate for mammography was significantly higher compared with mri . although it is expected that the sensitivity for mri in both the control group and the brca - mc is higher compared with mammography , no significant difference was found in this study within the two groups . described in their mammographic study on brca1 and brca2 mutation carriers a sensitivity of 64% for the detection of a tumor in the original reports . in this study , since this was a retrospective study and the radiologist was aware of the fact that a tumor was present at the time of the evaluation , no conclusion can be drawn from the difference in detection between both studies . on mammography , the mass like lesions detected in the brca - mc group were significantly more often described as rounded . also , lesions were found to differ in margin appearance ; tumor margins in the brca - mc group were significantly more often described as sharp . a smooth , nonspiculated mass has previously been described by tilanus et al .   as a reason for a false - negative mammographic evaluation in brca - mc . thus , although sickles et al .   described that nonpalpable , circumscribed , noncalcified breast masses ( probably benign ) should be managed with periodic mammographic surveillance regardless of lesion size and patient age , and sardanelli et al .   published that both the well - defined margins and the rounded shape are more often associated with benign lesions , these findings are not applicable to the brca - mcs studied in this or other studies on this subject . .   stated that any mammographic mass in brca - mcs must be regarded with suspicion . an additional evaluation using ultrasound and biopsy of all lesions detected in brca - mc is mandatory , regardless of their morphological appearance . in their study of 28 brca - mcs , hamilton et al .   also described the appearance of breast tumors on ultrasound . on ultrasound , 53% of the tumors were classified as either benign or indeterminate , making a biopsy of any detected mass inevitable . we are also of the opinion that any solid lesion detected in brca - mcs should be evaluated by a biopsy . in the screening of women with an increased risk for developing breast cancer , more tumors are detected by mri compared with mammography [ 8 , 9 ] . in this study , mri is known to have a lower sensitivity in detecting dcis compared with invasive carcinomas , especially in low - grade dcis . the low or intermediate contrast uptake that is often observed in pure dcis and the absence of a type 3 curve can result in a false - negative evaluation . kriege et al .   found in the screening of 1,909 women with an increased risk for developing breast cancer , including 358 carriers of germ - line mutations , that mri missed five cases of dcis that were detected on mammography , with six noninvasive tumors detected in total in the study . however , kuhl et al .   reported mri to be more sensitive for dcis compared with mammography in a prospective study of women with an increased risk for developing breast cancer . although mri proved to be more sensitive for the detection of dcis compared with mammography , not all cases of dcis were detected by either modality . therefore , at this point both modalities are still needed in the screening of women with an increased risk for developing breast cancer . similar to mammography , on mri a significantly higher number of lesions were described as rounded and with sharp margins in the brca - mc group . rim - enhancement was found to be significantly higher in the brca - mc group . the presence of this enhancement pattern has been associated with malignant lesions [ 26 , 27 ] . because mri enables the radiologist to evaluate the enhancement pattern of the lesion , where mammography does not , these lesions will become more suspectedly malignant , even though other morphologic features are more often seen in benign lesions . 1 ) with central necrosis or insufficient microvessel growth can be an indicator for the growth rate of tumors . jimenez and coworkers have described centrally necrotizing carcinomas to have an accelerated clinical course and early systemic metastasis . an accelerated growth rate can be associated with a high mai . in this study , this is in agreement with tilanus et al . , who also found the mitotic count to be significantly higher in tumors found in gene mutation carriers . the higher rate of sharp tumor margins and rim - enhancement may thus be explained by the more aggressive nature of tumors in brca - mcs . several authors have implied that , due to the rapid growth rate of tumors in gene mutation carriers , the screening frequency should be adjusted [ 13 , 29 ] . suggest a higher screening frequency in carriers because of the high number of interval cancers found in their group . mammography in carriers is not sensitive , particularly because the women are young and thus more often have dense breasts [ 30 , 31 ] . the use of mri in screening has already been a step forward since mri can detect smaller tumors , often occult for mammography , that are less likely to have progressed into lymph - node involvement . 1a an mlo mammogram from the right breast of a 42-year - old brca1-mutation carrier . an 11-mm sharply delineated rounded lesion is present on the mammogram projecting over the upper quadrants ( arrow ) . on mri , ultrasound guided core biopsy proved this lesion to be an invasive duct carcinoma a an mlo mammogram from the right breast of a 42-year - old brca1-mutation carrier . b a coronal subtraction mr image of the same breast . an 11-mm sharply delineated rounded lesion is present on the mammogram projecting over the upper quadrants ( arrow ) . on mri , ultrasound guided core biopsy proved this lesion to be an invasive duct carcinoma rounded , homogeneous enhancing lesions found on mri are in general not considered suspicious . a homogeneous enhancement pattern , found in nine brca - mcs , does not contribute to the malignant nature of these lesions . the dynamic analysis showed in both the brca - mc and the control groups a type 3 curve in , respectively , 82% and 71% of the cases . as described by kuhl et al . , a type 3 enhancement curve is highly indicative for malignancy . using this characteristic , even rounded , sharply delineated , homogeneous enhancing lesions become suspect malignant ( fig .  2 ) . 2a a coronal subtraction mr image from the right breast of a 49-year - old brca1-mutation carrier . lateral located in the right breast , a sharply delineated rounded , homogeneous enhancing lesion is visible with a longest diameter of 9  mm ( arrow ) . b the relative enhancement versus time curve . the type 3 curve seen for this lesion was the only characteristic indicating a possible malignancy . pathology proved this lesion to be an invasive duct carcinoma a a coronal subtraction mr image from the right breast of a 49-year - old brca1-mutation carrier . lateral located in the right breast , a sharply delineated rounded , homogeneous enhancing lesion is visible with a longest diameter of 9  mm ( arrow ) . b the relative enhancement versus time curve . the type 3 curve seen for this lesion was the only characteristic indicating a possible malignancy . pathology proved this lesion to be an invasive duct carcinoma despite all the findings discussed in this study , it remains questionable if the characterization of a lesion detected on either mammography or mri in brca - mcs is even necessary . as the chance for these women to develop breast cancer is significantly increased , almost any detected lesion will in practice be classified as suspect malignant until proven otherwise . found a positive predictive value for mr in women with an increased risk of only 53% due to a high number of false positives . as stated previously for mammographically detected lesions , additional evaluation by core biopsy is the only definitive classification for lesions detected in this group of women . in the case of mri screening in high risk women , short - term follow - up , target ultrasound or mri - guided biopsies are therefore often indicated . what the best strategy in this group of women will be , also in terms of cost effectiveness , needs to be further studied . we conclude that in brca - mc malignant lesions frequently have morphological characteristics that are commonly seen in benign lesions , like a rounded morphology or a sharp delineation . however , the possibility of mri to evaluate the enhancement pattern and enhancement kinetics of lesions enables the radiologist to detect characteristics suggestive for a malignancy .