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1
Radiology Imaging Associates and The Sally Jobe Breast Center, 8200 E.
Belleview Ave., Englewood, CO 80111.
2
Present Address: Wellspring Breast Center, Physicians Building South,
Community General Hospital, 4000 Broad Rd., Syracuse, NY 13215.
Received May 17, 1999;
accepted after revision November 3, 1999.
Supported by DuPont Merck Pharmaceuticals, North Billerica, MA.
Abstract
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SUBJECTS AND METHODS. Twenty-five patients with 33 biopsy-proven breast lesions underwent both scintimammography and sonography. Lesions were categorized as benign or requiring biopsy on the basis of the absence or presence of a focus of increased activity on scintimammography and the shape, orientation, and echogenicity of the lesion on sonography.
RESULTS. Sensitivity and specificity in detecting breast cancer were 92% and 95%, respectively, for scintimammography and 100% and 48%, respectively, for sonography. The higher specificity of scintimammography was statistically significant (p < 0.01).
CONCLUSION. Although the overall accuracy of 99mTc-sestamibi scintimammography in the diagnosis of breast cancer was high, it has several disadvantages in comparison with sonography. Scintimammography has a slightly higher false-negative rate for breast cancer, is unable to reveal cysts, is more expensive, takes longer to perform, and involves ionizing radiation. For these reasons, scintimammography with 99mTc- sestamibi is unlikely to either replace sonography or be frequently used in addition to sonography.
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99mTc-Sestamibi Scintimammography
Twenty microcuries (740 MBq) of 99mTc-sestamibi was IV injected
in the arm contralateral to the breast with the abnormality. Scintimammography
was performed using a single-head gamma camera equipped with a high-resolution
collimator (Dyna camera 4C; Picker, Cleveland, OH). Lateral decubitus and
anterior supine acquisition images were obtained 10 min after the injection.
For the lateral decubitus imaging, the patient lay on her side with the camera
positioned under the imaging table, and a lead apron was draped over the
upside breast to prevent radiation of the upside breast from reaching the
gamma camera. All images were acquired using a 20% window centered at 140 keV.
Images were reviewed by one of the non-nuclear medicine radiologists involved
in the study before biopsy to ensure that any abnormality on scintimammography
corresponded to the imaging or clinical finding.
Sonography
Real-time sonography was performed with either a 7.5- or 10-MHz transducer
(5200 or Performa; Acoustic Imaging, Tempe, AZ). Imaging of the area of the
breast revealed by mammography or clinical examination was performed in a
standard systematic fashion.
Breast Biopsy
Percutaneous sonographically guided core biopsy was performed on each
patient after scintimammography using a "long-throw" 14-gauge
automated core biopsy device (Monopty; Bard Radiology, Covington, GA) or an
11-gauge Mammotome (Biopsys Medical, Ethicon Endo-Surgery, Cincinnati, OH).
The sonographically guided 14-gauge core biopsy technique is well known
[12]. The sonographically
guided mammotomy technique is relatively new. Briefly, the mammotome driver is
held by an articulated arm attached to the sonography examination table and
the radiologist uses real-time sonography to guide the mammotome probe to a
position just posterior to the lesion to be biopsied. Once the mammotome is in
the desired position, the articulated arm is locked in place. The mammotome
biopsy can then proceed in a fashion similar to that of a stereotactic
mammotome biopsy, although the progress of a sonographically guided mammotome
biopsy can be continually monitored with real-time sonography
[13].
Image Evaluation
The scintimammograms were evaluated independently by two radiologists
experienced in nuclear medicine who were unaware of the sonographic and
pathologic results and the location of the lesions. The lesions were graded on
a four-point scale: grade 0, normal; grade 1, low focal uptake; grade 2,
medium focal uptake; and grade 3, high focal uptake. All patients with grades
1-3 uptake were considered positive, or suspicious for malignancy, requiring
biopsy. Diffuse bilateral uptake was considered negative. Disagreements were
resolved by consensus of the two radiologists.
The sonographic studies were reviewed independently by two radiologists experienced in sonography of the breast who were unaware of the scintimammographic and pathologic results but had knowledge of the location of the lesions. (Knowledge of lesion location is required before any breast sonography is performed and evaluated because it is a targeted examination and not a global examination of both breasts.) The lesions were graded according to standard American College of Radiology grading: grade 3, probably benign; grade 4, indeterminate or suspicious; and grade 5, highly suggestive of malignancy. Again, disagreements were resolved by consensus.
Statistical Analysis
Sensitivity, specificity, accuracy, positive predictive value, and negative
predictive value were calculated using standard formulas. The results were
compared using the chi-square test.
Cost Analysis
The charge for scintimammography was taken from the literature
[14]. (We used the literature
for calculation of this charge because the Sally Jobe Breast Center does not
have a charge for the scintimammography procedure. The only scintimammograms
performed at our center were for the purposes of this study and the patients
were not charged for the examination.) Charges for breast sonography and
percutaneous sonographically guided breast biopsy including pathologic
diagnosis were those current at our institution in 1998.
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Pathology
Of the 33 lesions that underwent core biopsy, 12 were malignant. Seven were
grade I infiltrating duct carcinomas (one was a mucinous carcinoma and one was
associated with duct carcinoma in situ). Four lesions were grade II
infiltrating duct carcinomas (three were associated with duct carcinoma in
situ). One was a pure duct carcinoma in situ
(Table 1).
Statistics
The sensitivity and specificity in detecting breast cancer were 92% and
95%, respectively, for scintimammography and 100% and 48%, respectively, for
sonography (Table 2).
Scintimammography had one false-negative finding, a 1.5-cm grade I
infiltrating duct carcinoma. Sonography had no false-negative results (Fig.
2A,2B,2C).
In addition, this lesion was not identified retrospectively on the
scintimammogram even with the knowledge of the lesion's location on sonography
and mammography. One patient had one false-positive result (fibrocystic
change) on scintimammography. Seven patients (11 lesions) had false-positive
results on sonography (Table 2)
(Fig.
3A,3B).
The difference in sensitivities was not statistically significant; however,
scintimammography was significantly more specific than sonography (p
< 0.01).
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Cost-Effectiveness
The charge for a breast sonography at the Sally Jobe Breast Center is $162.
The charge for scintimammography reported in the literature is $600
[13]. Our charge for a biopsy
including pathology is $1057 with sonographic guidance and $1389 with
mammotome. These charges do not reflect actual reimbursement, which is
considerably lower in the managed care environment. The total cost and cost
per breast cancer identified by sonography alone, scintimammography alone, or
both is shown in Table 2. Of
the 23 biopsies that would have been performed using sonography alone, 18 were
core needle biopsies, and five were mammotome biopsies. Of the 12 biopsies
that would have been perfoemed using scintimammography alone, nine were core
needle biopsies, and three were mammotome biopsies.
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In fact, when one looks at the cost of the different possible pathways using these two techniques, it can be argued that even with the increased number of false-positive results associated with sonography, one saves money by performing only sonography (without scintimammography) on questionable breast masses followed by sonographically guided core or mammotome biopsy ($2502 per cancer found) compared with performing scintimammography without sonography and sonographically guided biopsy of abnormal scintimammographic masses ($2607 per cancer found) (Table 2). Thus, even if one did not routinely perform sonography in the setting of an indeterminate or suspicious mass and went straight to scintimammography, it would be less cost-effective than using sonography as the primary determinant of whether a given mass required biopsy. In reality, though, even if sonography is not performed before or in addition to the scintimammography, a patient with a clinically or mammographically indeterminate or suspicious mass and positive scintimammographic findings should almost always undergo breast sonography before biopsy. This is necessary for at least four reasons. First, sonographically guided percutaneous biopsy should be the first choice for biopsy of a mass because it is less expensive than stereotactically guided percutaneous biopsy and far less expensive than a surgical biopsy. Second, it is ill-advised to biopsy soft-tissue-density masses with stereotactic guidance rather than sonography guidance because the local anesthetic administered before a biopsy can obscure the lesion on mammography. This obscuration does not occur with a sonographically guided biopsy of a mass. Third, before performing a sonographically guided biopsy of a mass, one must first perform diagnostic sonography to ensure mammographic sonographic correlation and to look for other unsuspected lesions that might need to be biopsied at the same time. Fourth, because a large percentage of all abnormalities on palpation and mammography are actually benign cysts or fibrocystic change that can be confidently diagnosed as benign on sonography, performing scintimammography without first performing sonography does not make sense. In light of these facts, if one chose to perform scintimammography as a part of a breast mass workup, one would almost certainly follow a pathway that would include sonography of the abnormal mass, then scintimammography, and then biopsy of any positive scintimammographic findings. This algorithm would be the most expensive pathway of all with a cost of $2975 per cancer found (Table 2). In addition, we found it inconvenient to stop the workup short of biopsy to perform scintimammography. For these reasons, routine scintigraphic evaluation of indeterminate breast lesions will probably need to await advances in tumor-seeking radiopharmaceuticals and improvements in gamma cameras.
Our study differs on several points from that of Burak et al. [11], the only previous study, to our knowledge, directly comparing scintimammography with sonography. The previous study reported a false-negative rate for sonography of 57%, ours was 0%. This difference reflects our use of dedicated breast sonography and newer criteria for categorizing breast lesions [2]. By adapting the criteria of Stavros et al. [2] to the American College of Radiology Breast Imaging Reporting and Data Systems (BI-RADS) classification (combining "indeterminate" and "probably malignant" categories of Stavros et al. into a single category corresponding to BI-RADS 4), we were able to designate more than 50% of solid breast lesions as BI-RADS category 3 (probably benign), thereby allowing imaging surveillance instead of biopsy. In addition, the study by Stavros et al. did not address the cost differential, nor did it discuss the relative ease of percutaneous breast biopsy versus the inconvenience of scintimammography in the workup of a breast lesion. However, we realize that centers without subspecialized sonographic and breast radiologists would be less likely to reproduce our high negative predictive value with breast sonography and that scintimammography may be more useful in that setting.
Even in the setting of high-quality breast sonography, a potential use for scintimammography might be in communities that do not have high-quality breast MR imaging [18]. We generally do not use breast MR imaging in the workup of an unbiopsied mammographic lesion; however, we have found breast MR imaging useful for surgical-treatment planning after the diagnostic workup and biopsy have been performed. Like scintimammography, breast MR imaging does not have a sufficiently high negative predictive value to preclude biopsy of a mammographically or sonographically indeterminate or suspicious lesion. Therefore, we do not stop our workup short of biopsy to perform a breast MR imaging to determine whether to biopsy a suspect lesion. However, in the setting of density on mammography and a biopsy-proven cancer, MR imaging is valuable in determining the true extent of the disease. Therefore, appropriate surgical therapy is more likely to occur at the outset (size of the lumpectomy, lumpectomy versus mastectomy, etc.). Scintimammography in settings in which high-quality breast MR imaging is unavailable may be similarly beneficial for treatment planning.
In conclusion, we found in this relatively small series that although scintimammography with 99mTc-sestamibi performed well with a high sensitivity and specificity, its negative predictive value was somewhat less than the 98% benchmark for avoiding biopsy. In fact, we are unaware of any published reports on scintimammography in which the negative predictive value was 98% or better (range, 82-96%) [5, 8,9,10,11, 16, 19,20,21]. In addition, the cost of performing scintimammography in the subset of patients whose masses remain indeterminate or suspicious after sonography would be higher than performing sonographically guided biopsy of these patients (although the small morbidity associated with a breast biopsy would be avoided in a significant number of patients). Ideally, breast diagnosis should progress in a stepwise, efficient fashion, with all elements of the workup, including biopsy, performed in one patient visit. Scintimammography is unlikely to either replace sonography for the evaluation of indeterminate breast lesions or be frequently used in conjunction with sonography, primarily because of its small false-negative rate. Improvements in radiopharmaceuticals and gamma cameras for imaging breast cancer may alter this assessment.
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