(Radiographics. 2001;21:641-655.)
© RSNA, 2001
Scintimammography in Patients with Minimal Mammographic or Clinical Findings1
Ruth L. Polan, MD,
Barry D. Klein, MD and
Roselyn H. Richman, MD
1 From the Department of Radiology, Los Robles Regional Medical Center, 227 W Janss Rd, Suite 150, Thousand Oaks, CA 91360. Presented as a scientific exhibit at the 1999 RSNA scientific assembly. Received May 8, 2000; revision requested September 25 and received October 26; accepted October 27. Address correspondence to R.L.P.
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Abstract
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A prospective study was made of scintimammographic findings obtained in 75 patients with minimal mammographic or physical examination findings. Patients included those with a new mammographic nodule or density (n = 33), indeterminate calcifications (n = 15), a palpable abnormality with normal mammographic findings and normal or inconclusive ultrasonographic findings (n = 13), or a new lump or mammographic change at the site of prior surgery (n = 14). A positive scintimammographic focus was defined as a discrete, rounded lesion with increased uptake and could have an intensity ranging from low to very high. Of the 30 cancers diagnosed, 27 demonstrated a positive scintimammographic focus. Eight of these foci represented occult cancers that were not identified at mammography or physical examination, and 11 were smaller than 1 cm (down to 4 mm). The overall sensitivity and specificity of scintimammography were 90% and 93.8%, respectively, which suggests that this modality may be useful in the early detection of breast cancer. It can also help distinguish postsurgical and post–radiation therapy changes from carcinoma and may be of value in certain high-risk patients. Scintimammography is a useful, noninvasive method of evaluating patients with low-suspicion or indeterminate mammographic or palpable findings and can help detect additional small tumors.
Index Terms: Breast, biopsy, 00.1261 • Breast neoplasms, 00.32 • Breast neoplasms, diagnosis, 00.11, 00.1216 • Breast neoplasms, radiography, 00.11 • Breast neoplasms, radionuclide studies, 00.1216 • Breast radiography, 00.11 • Cancer screening, 00.11, 00.1216
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Introduction
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Routine physical examination and mammography remain the methods of choice in screening for breast cancer. The sensitivity of mammography is high in this context (1,2); however, its specificity is limited: Only one-third of breast biopsies performed for an abnormal mammogram demonstrate malignancy (3).
Recent studies have reported favorable sensitivity (84%–96%) and specificity (72%–94%) for scintimammography performed with technetium (Tc)–99m sestamibi, in the diagnosis of breast cancer (4–7). The patient population in these studies consisted of women who presented with a suspicious palpable or mammographic lesion. The aim of our study was to assess the value of scintimammography in evaluating women with minimal (and, therefore, equivocal) mammographic or clinical findings.
In this article, we describe the scintimammographic technique used in our study. We also discuss and illustrate our findings in each of four categories: patients with a new mammographic nodule or density (n = 33), patients with indeterminate calcifications (n = 15), patients with a palpable abnormality with normal mammographic findings and normal or inconclusive ultrasonographic (US) findings (n = 13), and patients with a new lump or mammographic change at the site of prior surgery (n = 14). In addition, we evaluate and discuss the sensitivity and specificity of scintimammography for each category separately and for all four categories combined (Table).
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Scintimammographic Technique and Interpretation
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Seventy-five patients who had equivocal mammographic or palpable findings underwent Tc-99m sestamibi scintimammography. Patients were injected with 20–30 mCi (740–1,110 MBq) of Tc-99m sestamibi, using the foot for venous access whenever possible. Patients were imaged immediately with a Starcam 3000 gamma camera (GE Medical Systems, Milwaukee, Wis) with a high-resolution collimator. Each scintimammographic acquisition lasted about 10 minutes. A plexiglass overlay with a small, 2-cm-thick pad and cutouts for the breasts was placed on the imaging table. A lateral oblique view of each breast was obtained with the patient in the prone position. A 90° lateral view of each breast was also obtained. In some cases, the lateral oblique view provided better visualization of a focus of uptake than did the 90° lateral view. An anterior view was obtained of both breasts simultaneously with the patient supine and with the arms raised above the head as well as at the sides, which helped distinguish adenopathy from skin folds on the resulting images. The mediastinum, axilla, and chest wall were also visualized in the anterior projection.
At scintimammography, a positive focus was defined as a discrete, rounded lesion with increased uptake. The intensity of a positive focus could vary from low to very high. A vague, poorly defined region of minimal uptake was seen in normal glandular parenchyma and was not considered positive. A scintimammogram was considered negative when no discrete foci of increased uptake were seen. Biopsy was performed for all positive foci. If there was a positive scintimammographic focus in either breast that did not correlate with earlier mammographic or physical examination findings, a skin marker was placed at the focus site by the technologist and radiologist with the patient still in position on the scanning table. The patient then immediately underwent US of the area along the skin marker to visualize and localize the lesion for eventual biopsy. The US transducer scanned from lateral to medial at the level of the skin marker, which allowed easy detection of the lesion. Additional mammographic views were also obtained using the previously placed skin marker as a guide.
Results were classified as true-positive if there was a positive scintimammographic focus that proved to be a histologically positive (cancerous) lesion at surgery. Results were classified as false-negative if a cancerous lesion had been preoperatively interpreted as negative at scintimammography. A positive scintimammographic focus with subsequent negative histologic findings for cancer was considered false-positive. Results were classified as true-negative if a histologically negative (benign) lesion had been interpreted as negative at preoperative scintimammography.
US of the breast was performed on a Logic 700 MR unit with a 12-MHz transducer (GE Medical Systems) or an Acuson unit with a 7-MHz linear transducer (Acuson, Mountain View, Calif). Mammography was performed with the Senographer DMR unit (GE Medical Systems).
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Category 1: New Mammographic Nodule or Density
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A total of 34 mammographic findings were seen in 33 patients. All patients underwent additional mammographic work-up before scintimammography was considered. This work-up included spot magnification compression views in the craniocaudal, lateral oblique, and 90° lateral projections and, when necessary, medial or lateral swing views and rolled images. At the time of work-up, all patients had undergone US evaluation with no suspicious masses seen. In most cases, US showed no abnormality, although in a few cases it demonstrated a vague hypoechoic area or beam attenuation with no mass identified. The 34 mammographic findings were further categorized as (a) a mammographic density in only one view (n = 7), (b) a confluent density in two views (n = 10), (c) a nodule or nodularity in two views (n = 13), or (d) architectural distortion in two views (n = 4).
Twenty patients had negative scintimammograms and chose not to undergo surgery for the mammographic abnormality. All 20 patients had stable findings over a 2- to 3-year follow-up period; in two cases, follow-up demonstrated resolution of the mammographic finding. The remaining 13 patients underwent a total of 18 surgical biopsies. Five biopsies were performed for mammographic findings that showed no abnormality at scintimammography and proved to be histologically benign (true-negative). The remaining 13 biopsies were performed for positive scinti-mammographic foci, 11 of which proved to be histologically malignant (true-positive) and two histologically benign (false-positive). Scintimammography depicted solitary and multicentric cancers not seen at mammography in five of the 13 positive scintimammographic foci (38%) (Figs 1 –7). Focal cancers (n = 11) ranged from 4 mm to 2 cm in diameter (mean, 0.88 cm; median, 7 mm). At histologic analysis, positive (cancerous) lesions included infiltrative ductal carcinoma and infiltrating lobular carcinoma. One of the two false-positive lesions was a nodule that proved to be a fibroadenoma 2 cm in diameter with focal florid epithelial hyperplasia. The other was an approximately 1.5-cm confluent density that proved to be mammary duct ectasia.
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Figure 1a. Case 1. Occult cancer of the left breast in a 47-year-old woman. (a) Craniocaudal mammogram of the right breast (left) demonstrates a new confluent density in the lateral portion of the breast (arrow). Compare the normal findings on the craniocaudal view of the left breast (right). (b) Mediolateral oblique mammogram of the right breast (left) shows the new confluent density in the upper portion of the breast (arrows). Compare the normal findings on the lateral oblique view of the left breast (right).
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Figure 1b. Case 1. Occult cancer of the left breast in a 47-year-old woman. (a) Craniocaudal mammogram of the right breast (left) demonstrates a new confluent density in the lateral portion of the breast (arrow). Compare the normal findings on the craniocaudal view of the left breast (right). (b) Mediolateral oblique mammogram of the right breast (left) shows the new confluent density in the upper portion of the breast (arrows). Compare the normal findings on the lateral oblique view of the left breast (right).
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Figure 2. Case 1. Lateral oblique (bottom left) and 90° lateral (bottom right) scintimammograms of the left breast show a focal area of increased Tc-99 sestamibi uptake (arrow). The right breast demonstrates no abnormal uptake on either the lateral oblique (top left) or 90° lateral (top right) view.
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Figure 4. Case 1. Radiograph of the left breast specimen obtained at excisional biopsy demonstrates a suspicious lesion 7 mm in diameter localized with a J wire with US guidance (arrows). The lesion proved to be infiltrating lobular carcinoma. Biopsy specimen of the density in the right breast (cf Fig 1) was benign.
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Figure 5. Case 2. Multifocal cancer of the left breast in a 68-year-old woman. Craniocaudal mammogram of the left breast (right) demonstrates a bandlike density laterally (arrow). Compare the findings on a left craniocaudal mammogram that was obtained 1 year earlier (left).
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Figure 6. Case 2. Longitudinal US image reveals a vague, 8-mm anechoic-hypoechoic abnormality in the upper outer quadrant of the left breast (arrows). Subsequent additional magnification mammograms obtained in the mediolateral oblique, craniocaudal, and 90° lateral projections (not shown) failed to demonstrate a definite lesion in two projections.
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Figure 7. Case 2. Lateral oblique scintimammogram of the left breast (right) shows three foci (arrows). The foci were removed surgically and represented three different cancers, each with different histologic characteristics and measuring 5 mm, 8 mm, and 1.5 cm in diameter, respectively. A lateral oblique view of the right breast is shown on the left.
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Benign lesions ranged from 6 mm to 1.5 cm in diameter (mean, 1 cm; median, 1.5 cm). For Category 1 lesions, scintimammography demonstrated a sensitivity of 100% and a specificity of 92.9%.
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Category 2: Indeterminate Calcifications
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Fifteen patients had calcifications and underwent a total of 25 biopsies. Magnification images were obtained for all clusters of calcifications to further clarify morphologic characteristics, and biopsy was performed for all clusters. Of the 15 patients, four had two or more discrete clusters of calcifications in different quadrants of one breast and three had bilateral clusters of calcifications. At the site of calcification, there were nine positive scintimammographic foci, eight of which proved to be histologically positive (true-positive) and one histologically negative (false-positive) for carcinoma. The remaining 16 clusters of calcifications were not seen at scintimammography; 14 of these 16 clusters were histologically negative for cancer (true-negative) and included ductal hyperplasia, fat necrosis, fibrosis with chronic inflammation, radial scar with hyperplasia, and fibroadenomatous nodules with cystic change. The remaining two clusters were histologically positive for noninvasive cancer (ductal carcinoma in situ) (DCIS) (false-negative).
Of the eight true-positive lesions, four proved to be invasive ductal carcinoma and four invasive ductal carcinoma with DCIS at histologic analysis. One patient with a single small cluster of calcifications had two positive foci at scintimammography that proved to be multifocal carcinoma. Of the two false-negative lesions, one proved to be DCIS with no invasive component and the other ductal hyperplasia at histologic analysis.
One patient with bilateral calcification had a positive scintimammogram for one breast and a negative scintimammogram for the other, representing a true-positive finding for one group of calcifications and a true-negative finding for the calcifications in the contralateral breast. Another patient who had developed recurrent calcification at the site of lumpectomy and radiation therapy for DCIS also developed calcification in the pectoral muscle (Figs 8–10). Scintimammographic findings were true-negative at the lumpectomy site and true-positive in the underlying pectoral muscle, where histologic analysis revealed invasive ductal carcinoma. To our knowledge, this is the first reported case of malignant calcification in the pectoral muscle. A previous article discussed benign microcalcification in the muscle (8).
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Figure 8a. Case 3. Metastatic invasive ductal carcinoma to the right pectoral muscle in a 51-year-old woman who had undergone lumpectomy and radiation therapy for DCIS 3 years earlier. (a) Mediolateral oblique mammogram of the right breast shows new calcifications at the surgical site (marked with wire on skin [long arrow]) and in the pectoral muscle and axillary nodes (short arrows). (b) Magnified image of the lumpectomy site allows better visualization of the calcifications (arrows).
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Figure 8b. Case 3. Metastatic invasive ductal carcinoma to the right pectoral muscle in a 51-year-old woman who had undergone lumpectomy and radiation therapy for DCIS 3 years earlier. (a) Mediolateral oblique mammogram of the right breast shows new calcifications at the surgical site (marked with wire on skin [long arrow]) and in the pectoral muscle and axillary nodes (short arrows). (b) Magnified image of the lumpectomy site allows better visualization of the calcifications (arrows).
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Figure 9. Case 3. Lateral oblique scintimammogram of the right breast (left) shows increased uptake throughout the pectoral muscle (arrows) but no abnormal uptake in the breast itself. This "linear" or bandlike uptake pattern corresponds to the shape of the pectoral muscle, the entire length of which contains calcifications. Compare the lateral oblique view of the left breast (right).
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Figure 10a. Case 3. (a) Radiograph of the pectoral muscle specimen obtained at surgical biopsy demonstrates heterogeneous calcifications that proved to be metastatic invasive ductal carcinoma. (b) Radiograph of a specimen from the lumpectomy site shows indeterminate calcifications that proved to be nonmalignant, the result of radiation therapy.
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Figure 10b. Case 3. (a) Radiograph of the pectoral muscle specimen obtained at surgical biopsy demonstrates heterogeneous calcifications that proved to be metastatic invasive ductal carcinoma. (b) Radiograph of a specimen from the lumpectomy site shows indeterminate calcifications that proved to be nonmalignant, the result of radiation therapy.
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The sensitivity of scintimammography for calcifications was lowered by the two false-negative cases, which proved to be DCIS with no invasive component at histologic analysis. As stated earlier, the true-positive cases all proved to be invasive ductal carcinoma, either alone or in combination with DCIS. This suggests that scintimammography for the evaluation of calcifications may not be reliable in identifying DCIS alone but can help correctly identify invasive ductal carcinoma or combined invasive ductal carcinoma and DCIS as well as calcifications related to benign causes. The clusters of calcifications seen at mammogram ranged from 3 mm to 3 cm in diameter (mean, 1.2 cm). The sensitivity of scintimammography for Category 2 lesions was 80%, and its specificity was 93.3%.
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Category 3: Palpable Abnormality with Normal Mammographic Findings and Normal or Inconclusive US Findings
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There were 13 patients with 13 palpable abnormalities in Category 3. At US, no discrete suspicious lesion was found at the site of the lump in any of these 13 patients. In fact, US findings were normal in nine of the 13 patients. Of the four remaining cases, two demonstrated attenuation of the US beam with no associated mass and two demonstrated a benign-appearing finding at the lump site, which was thought to be a cyst with thick fluid in one case and most likely fibroadenoma in the other.
Five of the 13 patients had normal scintimammographic findings and chose not to undergo surgery. These five patients had stable mammographic and physical examination findings over a 2-year follow-up period and included one patient with resolution of the lump.
The remaining eight patients underwent a total of 11 biopsies. These eight patients had four negative scintimammographic foci, one of which was histologically positive (false-negative) and three histologically negative (true-negative) for carcinoma. Seven biopsies were performed for seven positive scintimammographic foci; six were histologically positive (true-positive) and one histologically negative (false-positive) for cancer.
Scintimammography depicted cancers that were not palpable and not seen at mammography in two of the seven positive scintimammographic foci (29%) (Figs 11–14). The two scintimammographically positive de novo lesions were subsequently identified at US after placing a skin marker at the site of the positive focus while the patient was still on the imaging table. However, although US helped identify the two de novo lesions, these lesions could not be identified on additional mammographic views even with magnification. The patient with a false-negative lesion coincidentally had one of the two de novo cancers identified by scintimammography in a different quadrant of the breast; consequently, therapy was changed from lumpectomy to mastectomy. The second de novo cancer identified at scintimammography was found in a different patient in the breast opposite the one with the palpable lump (true-negative lesion).
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Figure 11. Case 4. Occult infiltrating ductal carcinoma of the right breast in a 46-year-old woman who presented with a lump in the lower inner left breast at physical examination. Mediolateral oblique (left) and craniocaudal (right) mammograms of the right breast demonstrate no abnormality.
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Figure 13. Case 4. US image obtained following scintimammography helps identify the lesion in the upper outer right breast (arrows). Subsequent magnification mediolateral oblique and craniocaudal views (not shown) demonstrated no abnormality.
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Figure 14. Case 4. Radiograph of the surgical specimen of the right breast lesion shows a spiculated mass 1.8 cm in diameter (arrows). The lesion proved to be infiltrating ductal carcinoma. Biopsy specimen from the lump in the left breast found at physical examination was benign.
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The cancers in Category 3 included invasive lobular and invasive ductal carcinoma, and focal cancers ranged from 1 cm to 3 cm in diameter (mean, 1.5 cm; median, 1.5 cm). The sensitivity and specificity of scintimammography for Category 3 lesions were 85.7% and 88.9%, respectively.
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Category 4: New Lump or Mammographic Change at Site of Prior Surgery
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Seven of the 14 patients in Category 4 had undergone prior lumpectomy for cancer, and seven patients had undergone excisional biopsy, which proved benign in all cases. In all 14 cases, US was inconclusive in distinguishing scar from a true mass. Two cancers were found in two patients with benign findings at prior biopsy. Both cases demonstrated a questionable mammographic change at the biopsy site with no palpable lump. Six patients—three of whom had undergone lumpectomy and three of whom had benign findings at biopsy—had a lump at the site of prior biopsy with no mammographic change. Eight patients—four of whom had undergone lumpectomy and four of whom had benign findings at biopsy—had a mammographic change at the biopsy site. Six patients underwent biopsy, four for palpable lesions and two for a questionable mammographic change at the biopsy site. Scintimammographic findings were positive in two patients and proved to be carcinoma (true-positive) at histologic analysis (Figs 15–17). Scintimammo-graphic findings were negative in four patients (those presenting with a palpable abnormality) and proved to be histologically benign (true-negative) (Figs 18–20). The two cancers in this category measured 5 x 2 mm and 7 x 3 mm, respectively and proved to be infiltrating ductal carcinoma. The lumps that were benign at biopsy or stable over a follow-up period of 2 years or more ranged from 7 mm to 2 cm in diameter (mean, 1.2 cm; median, 1 cm). The overall sensitivity and specificity of scintimammography for lesions in this category (including new mammographic findings or a new lump) were both 100%.
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Figure 15. Case 5. Invasive ductal carcinoma in a 74-year-old woman with a history of seven biopsies of the tail of the right breast (all benign). The patient had also undergone partial left mastectomy for breast carcinoma many years earlier. Mediolateral oblique mammograms of the right breast obtained in 1993 (left) and 1998 (right) demonstrate possible increased stranding on the later image at the site of the prior biopsies (arrows). It was uncertain whether this change was related to a slight difference in patient position.
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Figure 16. Case 5. Invasive ductal carcinoma in a 74-year-old woman with a history of seven biopsies of the tail of the right breast (all benign). The patient had also undergone partial left mastectomy for breast carcinoma many years earlier. Lateral oblique scintimammogram of the right breast demonstrates a focus of increased uptake in the tail (arrows). The lateral oblique view of the left breast is shown at the right.
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Figure 17. Case 5. Invasive ductal carcinoma in a 74-year-old woman with a history of seven biopsies of the tail of the right breast (all benign). The patient had also undergone partial left mastectomy for breast carcinoma many years earlier. Radiograph of the surgical specimen from the right breast shows a faint density measuring 7 x 2 mm (arrows). This finding proved to represent invasive ductal carcinoma.
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Figure 18. Case 6. True-negative findings in a 62-year-old woman who developed a lump in the right axillary region shortly after undergoing right mastectomy and beginning radiation therapy. The patient had undergone left mastectomy several years earlier. Mediolateral oblique mammogram demonstrates a suspicious oval density with stranding (arrows), findings that corresponded to a lump found at physical examination.
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Figure 19. Case 6. True-negative findings in a 62-year-old woman who developed a lump in the right axillary region shortly after undergoing right mastectomy and beginning radiation therapy. The patient had undergone left mastectomy several years earlier. Longitudinal US image demonstrates a solid lesion with irregular margins. The differential diagnosis includes carcinoma and hematoma.
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Figure 20. Case 6. True-negative findings in a 62-year-old woman who developed a lump in the right axillary region shortly after undergoing right mastectomy and beginning radiation therapy. The patient had undergone left mastectomy several years earlier. Ninety-degree right lateral (top) and anterior (bottom) scintimammograms show no focal uptake in the right axilla; in fact, a "cold" oval area is seen on the lateral view (arrows). Surgical excision revealed only benign findings, including hemosiderin deposition, foreign-body giant cell reaction, and fat necrosis.
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Conclusions
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In our study, we prospectively investigated the value of scintimammography in low-suspicion or indeterminate, nonpalpable, screening-detected abnormalities as well as in indeterminate palpable findings. Our results—a sensitivity and specificity of 90% and 93.8%, respectively—suggest that scintimammography is useful in early detection of breast cancer and simultaneously decreases the number of unnecessary biopsies. Eight of the 27 true-positive scintammographic foci proved to be occult cancers that were not seen at initial conventional mammography or physical examination. These cancers were identified due to the ability to image both breasts at scintimammography for possible occult multifocal, and multicentric cancer. Another benefit of scintimammography is the capacity to help distinguish postsurgical and post–radiation therapy changes from carcinoma. The proposed mechanism of uptake of Tc-99m sestamibi is believed to be related to mitochondrial uptake, with greater mitochondrial density in breast cancer cells. The effects of neovascularity seem less significant than the influence of the mitochondria and could explain the low number of false-positive findings at scintimam-mography (7,9). Previous studies have found scintimammography to be excellent for lesions larger than 1 cm (10). Our study would indicate that scintimammography is also excellent for lesions smaller than 1 cm: Of the 27 cancers detected with scintimammography, 11 were smaller than 1 cm, and none of these were palpable. Finally, scintimammography may be a useful adjunct in high-risk patients such as those with prior breast cancer, lobular cancer in situ, Paget disease, or a very strong family history of breast cancer.
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Footnotes
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See the commentary by Kotlyarov
following this article.
Abbreviation: DCIS = ductal carcinoma in situ
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References
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Abstract
Introduction
