Download Abstract Introduction A. K. Kelekar, S. Mukherjee, C. Mitri, F. Khan, W

MRI Characteristics of BRCA – Associated Breast Cancers
A. K. Kelekar, S. Mukherjee, C. Mitri, F. Khan, W. Ducaine, L. Dohany, D. Zakalik
Abstract
Background:
Magnetic Resonance Imaging (MRI) is the preferred imaging modality for
screening and diagnosis of breast cancer in BRCA-1 and BRCA-2 mutation
carriers. However, there is limited data on the radiographic features of
BRCA1/2-positive breast cancers on MRI. This study evaluates the MRI
characteristics of BRCA1/2 -related breast cancers.
Methods:
All female BRCA mutation carriers with a biopsy proven breast cancer,
imaged with MRI for screening or preoperative evaluation at William
Beaumont hospital between April 2002 until January 2011, were included
in the study. A total of 47 mutation carriers were identified. All MRI
examinations were retrospectively evaluated by an independent radiologist
for the following characteristics: shape, margin, enhancement, T2
intratumoral intensity.
Results:
A majority of BRCA- associated breast tumors were morphologically
irregular, T2 hypointense lesions on MRI with heterogeneous enhancement.
No statistically significant differences were noted among the BRCA-1 and -2
mutations carriers.
Conclusions:
Previous studies have reported that BRCA-associated breast cancers
demonstrate morphological characteristics that resemble benign tumors
i.e. round shape and smooth margins. Our study however, showed features
more typical of malignant lesions i.e. irregular shape and margin. Low T2
intratumoral intensity tumors were commonly seen in our cohort, although
BRCA-1 patients often develop triple negative tumors which typically are
high intensity. These differences may be explained by small sample size or
population differences. Future research is needed with larger patient cohorts
to elucidate the unique MRI characteristics of BRCA- related cancers.
MRI Characteristic
SHAPE
Round
Lobulated
Irregular
BRCA-1
3
8
19
BRCA-2
4
3
12
BRCA1+2
7 (14.3%)
11 (22.4%)
31 (63.3%)
MARGIN
Smooth
Irregular
3
26
3
17
6 (12.2%)
43 (87.8%)
5
19
5
2
13
5
7 (14.3%)
32 (65.3%)
10 (20.4%)
ENHANCEMENT
Homogenous
Heterogeneous
Rim
T2 INTRATUMORAL
INTENSITY
Low
Equal
High
25
4
1
21
0
2
46 (86.8%)
4 (7.6%)
3 (5.7%)
• Several studies have demonstrated that Magnetic
Resonance Imaging (MRI) is the preferred imaging
modality for screening and diagnosis of breast cancer in
BRCA-1 and BRCA-2 mutation carriers.(3-5)
• These studies, comparing the various imaging modalities
in BRCA mutation carriers, show contrast enhanced
MRI to be more sensitive than mammography, breast
ultrasound or clinical breast exam. However the
specificity of MRI is lower than mammography, breast
ultrasound and clinical breast examination respectively.
(3-5)
Results
• The following terminology was used for describing the features of breast cancers on MRI:
- Mass shape: Round or oval, lobulated or irregular
- Mass margin; Smooth (if well defined) or irregular (if ill defined)
- On unenhanced T2 weighted fat suppressed images, the lesions were described as low,
equal or high intensity in comparison to normal breast tissue.
- Contrast enhanced T1-weighted images were described based on patterns of early
enhancement as homogenous, heterogeneous or rim enhancement.
• Dynamic changes of enhancement were not analyzed.
• Use of MRI for surveillance can result in the diagnosis
of familial cancers at an earlier stage.(3) Hence, current
guidelines recommend use of MRI for surveillance in
women with a high risk of developing breast cancer.(6)
• Two cases of non mass enhancement were identified which could not be described with the
above characteristics, hence they were excluded for the study.
• Review of literature yields few studies exploring the
radiographic features of BRCA associated breast cancers
on MRI.
Table 1: MRI characteristics
Methods
• 276 females diagnosed with BRCA- associated breast
cancer at the Cancer Genetics Program at William
Beaumont Hospital between April 2002 and January
2011 were included in the study.
• On review of the electronic medical records, 47 patients
with 49 tumors were identified who had biopsy-proven
breast cancer and underwent preoperative MRI.
• Bilateral breast MRI’s were performed using an MRI
machine with the following specifications:
- Magnetic field strength= 1.5 T and 3 T of the older
and newer machine respectively.
- Homogenous magnetic field
- Bilateral imaging
• Two patients had locally recurrent breast cancers and each lesion was separately analyzed.
BRCA-1
BRCA-2
p (Chi square)
for BRCA-1 vs.
BRCA- 2
Round
3
4
Lobulated
Irregular
8
19
3
12
Total=49
0.45
(not significant)
Smooth
3
3
Irregular
26
17
Total=49
MRI Characteristic
SHAPE
MARGIN
ENHANCEMENT
Homogenous
5
2
Heterogeneous
Rim
19
5
13
5
Total=49
T2 INTRATUMORAL INTENSITY
Low
25
21
Equal
High
4
1
0
2
Total=50
(Extra case of linear
enhancement)
- Contrast-enhanced imaging with gadolinium chelate
- Unenhanced T2-weighted fat-suppressed imaging
- Assessment of lesion morphology adhering to the
following criteria: Small pixel size (< or equal to 1
mm), thin section thickness (< or equal to 3 mm)
• Lesion enhancement kinetics were not evaluated, as
MRI’s done prior to June 2010 did not consistently
perform or report the findings.
Total BRCA positive patients
BRCA-1
BRCA-2
Total Tumors analyzed
Mean age of patient
Introduction
Pure DCIS(Ductal carcinoma insitu)
DCIS+ invasive cancer
Invasive cancer
• The breast cancer susceptibility genes, BRCA-1 and -2,
are believed to be responsible for majority of hereditary
breast/ovarian cancer.(1)
• Differences in MRI findings between BRCA-1 and
-2 associated cancers was evaluated for statistical
significance (p<0.05) using the Chi square test (with
graph pad prism software).
Average size of tumor
• The protocol for this retrospective study was approved
by the Human Investigation Committee of the William
Beaumont Hospital.
0.53
(not significant)
0.47
(not significant)
0.09
(not significant)
Total
(BRCA1+2)
percentage
7
14.3
11
31
22.4
63.3
6
12.2
43
87.8
7
14.3
32
10
65.3
20.4
46
86.8
4
3
7.6
5.7
• A majority of BRCA- associated breast tumors had
irregular shape, irregular (ill defined) borders and
appeared as T2 hypointense lesions on MRI with
heterogeneous enhancement.
• No statistically significant differences were noted among
the BRCA-1 and -2 mutations carriers with respect to the
above mentioned features.
• A significantly high percentage (61.9%) of DCIS either
alone or in combination with invasive cancer was noted
in our study cohort.
• Triple negative tumors occurred in 69% of BRCA-1
patients and 33.3% of BRCA-2 patients.
Figure 1.
The most common MRI finding in our patients: Irregular shape and
margin with heterogeneous enhancement.
Conclusions and Discussion
• The majority of BRCA related tumors had irregular shape and margin, features that are
often associated with sporadic malignant breast cancers.
• This was in contrast to previous studies which have described BRCA-associated breast
cancers to have features closely resembling benign tumors such as rounded lesions with
sharp, well defined margins.(7)
• A possible explanation for this observation could be a higher proportion of DCIS tumors
(61.9%) compared to previous reports (37%), leading to a characteristic radiographic
appearance.(8)
• Most cancers in our study demonstrated heterogenous intratumoral enhancement. Prior
studies have demonstrated both rim enhancement and heterogenous enhancement with
equal frequency.(7)(9)
• MRI appearance of tumors in this study was predominantly low intensity on T2 weighted
images. Previous studies have reported both low and high T2 weighted signal intensity in
BRCA associated breast cancers.(7)(9)(10)
• Despite having a higher frequency of triple negative breast tumors in our cohort, our
patients did not demonstrate the previously described characteristics of triple negative
tumor i.,e smooth margins, ring enhancement and high intratumoral intensity.
• The differences between our study findings and prior reports may be explained by small
size or population differences.
Figure 2.
The most common MRI finding previously described in BRCA patients
and encountered less frequently in our cohort: Round shape, smooth
margin. This lesion shows homogeneous enhancement.
• MRI findings of BRCA related breast cancers demonstrate variable characteristics. Hence
any abnormality detected on MRI should be viewed with suspicion in these high-risk
patients and warrant biopsy for histopathologic confirmation
• One of the limitations of this study was the inability to assess dynamic enhancement
kinetics. Prior research has demonstrated similar enhancement kinetics i.e. type 3 curve or
washout pattern, between BRCA mutation carriers and non carriers, although this was not
able to be evaluated in the current study.(7)
• Future research is needed to further elucidate the unique MRI characteristics of BRCArelated cancers.
References
Table 2: Patient characteristics
• The selected MRI images were reviewed by an
independent radiologist blinded to the BRCA mutation
status of the breast cancer patients.
• For BRCA-1 mutation carriers the risk of developing
breast cancer by age 70 years is 65% (95% confidence
interval 44%-78%). The risk for BRCA2- mutation
carriers is 45% (31%-56%). The risk is estimated to be
higher if the index breast cancer case was diagnosed at an
age less than 35 years.(2)
Beaumont Hospital,
Royal Oak, MI
47
29
18
49
44.7 years
3
26
18
1.6 cm
BRE Grade 1
BRE Grade 2
BRE Grade 3
3
18
24
Triple negative (total)
Triple negative BRCA-1
Triple negative BRCA-2
Lymph node involvement
Tumor Necrosis
26
20
6
18
7
Figure 3.
Irregular shape and margin with rim enhancement: Typical features of
sporadic malignant breast cancer.
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