Research Article
Pre-Operative MRI Exhibits Limited Utility in Axillary Staging for Breast Cancer
John Kuckelman*, Morgan Barron, Jason Bingham, Andrew Mosier and Vance Sohn
Department of Surgery and Radiology, Madigan Army Medical Center, USA
*Corresponding author: John Kuckelman, Department of Surgery, Madigan Army Medical Center, 9040-A Fitzsimmons Avenue, Tacoma, Washington 98431, USA
Published: 27 Dec, 2016
Cite this article as: Kuckelman J, Barron M, Bingham
J, Mosier A, Sohn V. Pre-Operative
MRI Exhibits Limited Utility in Axillary
Staging for Breast Cancer. Clin Surg.
2016; 1: 1265.
Abstract
Introduction: Magnetic resonance imaging (MRI) is commonly utilized in treatment planning for breast cancer patients. While axillary lymph node findings are routinely reported in these studies,
the utility of these findings remains unclear.
Methods: In this retrospective study from 2008-2014, women diagnosed with invasive breast cancer
who did not undergo neoadjuvant therapy were reviewed.MRI characteristics of axillary findings
were compared to the final pathologic results.
Results: 218 of 338 female patients met inclusion criteria and comprised our patient cohort. MRI
was found to have a sensitivity and specificity of 49% and 78%, respectively. The negative predictive
value was 80% with an accuracy of 71% and a false negative rate of 13.8%. MRI was more often
accurate in younger patients (p< 0.04, CI 0.52-1.19) and those whom had a larger number of lymph
nodes harvested (p< 0.0001, CI -10.8 to -0.2). True positives had significantly larger primary tumors
and a larger number of positive lymph nodes on final pathology.
Conclusion: MRI of the axilla is not a reliable tool for axillary staging in women with breast cancer.
Keywords: Invasive breast cancer; Magnetic resonance imaging; Axillary staging; Sentinel lymph node biopsy
Introduction
Breast conservation therapy (BCT) and the use of sentinel lymph node biopsy have become
standard of care in the workup and treatment of invasive breast cancer (IBC). Recently, trends have
favored minimal surgical management in the treatment and staging of IBC [1]. This is particularly
evident in the surgical management of the axilla. The Z0011 trial showed no survival benefit when
performing full axillary dissections in patients having axillary lymphaticmetastasis determining
that there was no added benefit of axillary dissection for those with micro-metastases (< 2 mm in
size) [2]. This, among other data, has changed the axillary management for women with IBC. These
surgical advances have paralleled increasing quality options for imaging of the breast and axilla.
Preoperative magnetic resonance imaging (MRI) of the breast for patients with suspected or known
IBC has become a very common modality used in this patient subset. The National Comprehensive
Cancer Network (NCCN), among other organizations, has outlined the patient population that
should undergo a preoperative MRI. Specifically, MRI is used in biopsy proven IBC when there is
concern for multifocal or multi-centric disease, and when findings on mammography or ultrasound
fail to fully delineate the extent of disease [3-5]. Still, many institutions more liberally apply the use of
preoperative MRI and obtain these studies in all patients diagnosed with IBC on core needle biopsy.
As a part of the study, radiologist will routinely comment on the axillary findings of these preoperative
studies; however, unlike axillary ultrasound, what constitutes “concerning characteristics” is not
well defined. Moreover, the clinical utility of these findings is poorly understood.
Our study sought to better define the role of axillary findings on preoperative MRI for patients
with confirmed IBC. Our hypothesis is that MRI has limited utility in identifying patients with
axillary metastasis and thus would not be able to aide in clinical decision making.
Table 1
Table 2
Methods
After obtaining Institutional Board Review approval, a retrospective chart review was performed
on a prospectively collected quality assurance database completed for patients undergoing work up
and treatment for invasive breast cancer at Madigan Army Medical Center from 2008-2014. Patients
selected for analysis included all female patients 18 years and older with biopsy proven infiltrating
ductal or lobular breast cancer. All patients had a preoperative
MRI completed within one month of their operation. Patients were
excluded if they had undergone neoadjuvant chemotherapy, had
alternate histology on final pathology, were male or did not receive
MRI prior to their index operation.
The operations performed (BCT versus mastectomy) as well as
the axillary procedure were decided by the patient in conjunction with
perioperative counseling with the operating surgeon. The amount of
axillary nodal tissue varied from sentinel lymph node sampling to
partial axillary dissections during mastectomy to complete axillary
dissection upon either grossly positive disease or positive nodal
disease on intraoperative frozen pathology evaluation. All care was
completed at our institution.
Radiology reports were reviewed from MRIs completed prior
to the surgical intervention. Our institution will obtain MRIs using
the guidelines set forth by the NCCN. All breast MRIs are read by
one of four fellowship trained breast imaging radiologist. Images
are obtained using the following standard protocol: Intravenous
contrast enhanced MRI of both breasts is performed on a Siemens
TrioTrim 3.0 Tesla Magnet using a 7 channel; In Vivo Breast Array
MR coil with the following pulse sequences: 3 Plane Localizer, T2
TIRM (STIR) Axial BLADE (FOV 340; Time to Repetition [TR]
11070; Time to Echo [TE] 137; 3 mm @ .8 mm Time=4:49), Axial T1
FL3D (FOV 340; TR 6.7; TE 2.63; 1.5 mm @ 20% Time=1:02), Axial
T1 FL3D (Q-fat saturation technique; FOV 340; TR 4.0; TE 1.4; 1.00
mm @ 20% Time=6:31 -1 run without and the remaining 5 runs after
contrast administration), and Sagittal T1 (FOV 240; TR 4.35; TE 1.75;
2.0 mm @ 20% Time=2:04). Images are reviewed on a dedicated Dyna
Cad workstation (Invivo Corp).
Our radiologists predominantly rely upon the Axial T1 FL3D
post-contrast sequences which have a special resolution of 1 mm.
This is double checked with the Sagittal T1 – 2 mm. Axillary findings
are considered abnormal if there is cortical thickening greater than 4
mm in both axial and sagittal planes and/or loss of the normal central
fatty hilum. Post lymph node biopsy changes are identified and not
considered as a positive axillary finding on MRI. Operative reports
and final pathology was reviewed for all diagnostic preoperative
breast biopsies as well as final histology for resected tumor and
axillary nodal tissue.
Simple statistical analysis was performed to define the
demographics and characteristics of our study group. Positive MRI
findings were compared to final lymph node pathology to determine
our primary endpoints of sensitivity, specificity, negative and positive
predictive values and well as accuracy and false positive rate of
axillary MRI. Secondary endpoints utilized comparison analysis of
our true positive group and different nodal staging to evaluate for
any significant differences from the total cohort for age, primary
tumor size, number of positive lymph nodes, and hormonal status.
Fishers exact, Student’s T-test, and one-way ANOVA tests were
performed to evaluate for any significant differences between and
within comparison groups. Statistical significance was defined as a p
value < 0.05 (CI95%). Data was compiled using Microsoft Excel 2011®
(Redmond, WA) and statistical analysis of continuous and categorical
data were carried out using SPSS v. 22 (IBM Corp., Chicago, IL).
Descriptive statistics calculated for continuous data included mean,
standard deviation, and percentage.
Results
A total 338 patients were identified as having undergone work
up for IBC. Of these, 120 patients were excluded for reasons outlined
in the methods section. Seventy seven out of 120(65%) patients were
excluded for not requiring preoperative MRI while 24(20%) received
neoadjuvant chemotherapy. Seventeen patients (14%) were excluded
due to having alternate histology on final pathology reports with
top two alternate types were mammary [6] and papillary [5] and the
remaining 6 being split between mucinous, inflammatory, adenoid
cystic and metaplastic sarcomatoid carcinoma. Two patients had
their index operation completed at an outside hospital leaving 218
patients meeting inclusion criteria for review. The demographic and
characteristic makeup of our cohort is summarized in Table 1. The
average age at diagnosis was 55 years old. The majority of patients
were diagnosed with invasive carcinoma (IDC) at 92.2% and 140 of
these patients underwent BCT (64%). Average tumor size was 1.8
cm (+/- 1.5 cm) and the average number of lymph nodes harvested
was 6.9 (+/- 8.1). With regards to hormonal status, 62.8% of patients
were found to be ER/PR positive with only 9 (4.1%) patients being
triple negative (- ER/PR/HER2). Sixty (27.5%) patients demonstrated
metastasis to at least one lymph node on final pathology with 8 of
those 60(13%) being micrometastasis or isolated tumor cells only.
Most patients (n=158, 73%) had N0 nodal staging with 21% (n=46)
patients had N1 disease and the remainder (n=14, 6%) had N2 or
greater nodal disease Table 2 .
Overall, the sensitivity of MRI in detecting axillary metastasis
was49% and the specificity was 78%. The negative predictive value
(NPV) and positive predictive value (PPV) were 80% and 46%,
respectively. The accuracy of MRI for detection of axillary metastasis
was 71%. These values were recalculated after excluding patients
with micrometastasis or isolated tumor cells only and were not
found to be significantly different. Further subgroup analysis was
performed comparing patients receiving MRI prior to biopsy versus
those receiving MRI after tissue biopsy. There were no statistically
significant differences when these groups were compared to each other
or in comparison to the overall sensitivity, specificity and accuracy.
Specific values can be found in Table 3. Nodal staging determined on
final pathology was assessed as well. Forty-three percent of patients
with N1 disease had positive axillary findings on preoperative MRI.
This increased to 71% with pathological staging of N2 or greater (p
>.001). False positive (N0) rate was 22%.
We looked specifically at the characteristics of our true positive
group and compared those to our total cohort. We found that MRI
was more often accurate in younger patients (p< 0.04, CI 0.52-1.19)
and those whom had a larger number of lymph nodes harvested
(p< 0.0001, CI -10.8 to -0.2). When comparing final pathology for
these two groups we found that patients were more often to have
true positive finding if they had more advanced disease. As shown in
Figure 1, as you might expect, our true positive group had significantly
larger primary tumors and a larger total number of positive lymph
nodes on final pathology.
Table 3
Discussion
A lessinvasive approach in the surgical management of the axilla
continues to be the trend for breast cancer. It has been nearly two
decades since the replacement of axillary lymph node dissection
(ALND) with sentinel lymph node biopsy (SLNB) resulting in
significantly less morbidity due to surgery of the axilla. Still, SLNB
carries a significant risk of lymphedema, as high as 8%, independent
of the inherent of surgery [6,7]. A favorable alternative to surgery
would require accurate staging of the axilla with noninvasive
imaging. Definitive identification of axillary metastasis could alter the
sequence of adjuvant therapies and make surgical intervention of the
axilla for staging purposes obsolete.
MRI has established itself in the preoperative staging and
surgical planning of rectal and endometrial adenocarcinoma.
Reliable identification of nodal disease is associated with a NPV of
approximately 95% in these populations and is crucial to appropriate
planning. Findings on MRI ultimately affect timing of adjuvant
therapy as well operative approaches for these malignancies [8,9].
Obviously, these cancers are vastly different from IBC in terms of
anatomic location, tumor behavior, and feasibility of surgical nodal
sampling. Nonetheless, the utility and impact of MRI for evaluation
of metastatic nodal disease in these disease sites is notable.
Current literature regarding the application of pre-operative
breast MRI for detecting axillary lymph node metastasis and guiding
surgical management is somewhat sparse and conflicting. Axillary
ultrasound has established that lymph nodes with absence of fatty
hilum, cortical thickening and non-hilar or trans-cortical vascular
flow are highly suspicious of metastatic development and often
targeted for needle directed biopsies. Absence of the fatty hilum is
likely the most specific finding associated with nodal metastasis.
Unfortunately this finding is not present often enough to be entirely
reliable [7,8]. Cortical thickening of >4 mm is another specific and
accurate indication of malignancy, especially in the setting of known
breast cancer [9]. Finally although not reproducible on MRI, nonhilar
(trans-cortical) vascular flow seen on ultrasound is highly
predictive of malignancy if seen with abnormal cortical thickening
[7,10]. MRI has been compared to ultrasound to determine which
modality is most accurate. These studies have shown no difference in
accuracy between modalities with percentages similar to our findings
[11]. Interestingly though, if positive findings are concordant between
the two modalities the sensitivity and PPV are improved [12]. Our
study suggests that the well-described characteristics for suspicious
lymphadenopathy on ultrasound cannot be directly applied to
findings on preoperative MRI.
In a study evaluating axillary focused MRI short and long axis
length, maximal cortical thickness, relative T2 value, loss of fatty
hilum (p< 0.001 for each), and eccentric cortical thickening (p<
0.003) were shown to be statistically significantly different between
the metastatic and non-metastatic axillary lymph nodes. Specificity
was ~90% when 4 of the previous findings were present [13]. Chung et
al. [14] reported similar findings showing that the mean size of nodes
is significantly larger in metastatic axillary nodes when compared to
benign lymph nodes in the axilla. Perhaps because of limited power,
other recent smaller studies have concluded that although breast
MRI has the potential to become a routine method for evaluating
the metastatic lymph nodes before submission to ALND, it is not yet
a valid alternative to histological analysis. SLNB affords the highest
sensitivity (93%) when compared to any current imaging modalities
including PET-CT and breast MRI [15,16]. Further studies evaluating
dynamic MRI imaging methods of the axilla determined that
quantitative MRI features shows little value in identifying axillary
metastasis [17].
Our study findings demonstrated that standard preoperative MRI
of the breast with inclusion of the axilla has inadequate specificity
and accuracy with poor sensitivity for the detection of malignant
pathology in the axilla. These findings were not significantly altered
when adjusting for and excluding patients having only micro
metastasis. Patients demonstrating positive axillary MRI findings
with corresponding disease on final pathology tended to be younger
women, with larger tumor size, and a higher number of lymph nodes
sampled on final pathology. This suggests that patients with more
aggressive tumors or those who present at a later stage will more often
have accurate MRI findings. This data leads us to conclude that there
are currently no specific tumor characteristics or patient populations
for which preoperative MRI of the axilla would be able to effectively
replace surgical sampling for staging.
The findings of our study are inherently limited as it is a
retrospective, single institution analysis therefore exposed to the
unavoidable biases associated with its data and analysis. This is
exemplified in that our chart review was unable to delineate specific
indications for obtaining preoperative MRI and as such we are unable
to more specifically characterize our cohort. Finally, the sequence
of preoperative work up and definitive treatment was not uniform
among our patients and thus makes our findings susceptible to
heterogeneity.
Conclusion
Our study finding strongly infers that the role for MRI is limited in the preoperative staging of the axilla in patients with IBC. Staging MRI demonstrated poor sensitivity, specificity, and accuracy in the detection of axillary metastasis in patients with infiltrating ductal and lobular breast cancer. This has the potential to change with the advancement of MRI protocols and modalities and should be further investigated through randomized prospective studies.
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