Functional breast imaging using the single photon technique.

Early diagnosis of carcinoma of the breast is currently attempted by mammography and physical examination which together have a sensitivity of 85%. Mammography has a positive predictive value of only 15 to 40 percent. The usefulness of scintimammography for the detection of carcinoma of the breast has been studied which demonstrated improved specificity compared to conventional mammography. In future, with the development or dedicated breast imager and new targeted radiopharmaceuticals, we can achieve detection of smaller than 1 cm carcinoma. This type of imaging enables us to detect cancer at its 'pre-anatomic' stage.

The role of nuclear medicine in breast cancer detection: functional breast imaging.

Mammography remains the imaging modality of choice in detection of early, nonpalpable breast cancer. Scintimammography using SPECT, however, may prove to be a very useful adjunct to a nondiagnostic or difficult mammogram. Further prospective studies have to be designed so that the specific clinical applications of this technique are more defined. As with any new imaging procedure, special care to obtain high-quality scintimammographic studies and sufficient training of staff to perform and interpret the imaging are necessary.

The clinical utility of Tc-99m sestamibi scintimammography in detecting multicentric breast cancer.

The ability to recognize multicentric breast cancer preoperatively would assist in identifying appropriate candidates for breast conservation surgery. Tc-99m scintimammography (SMM) is an adjunct to conventional mammography in identifying selected patients with breast cancer. The purpose of this study is to report the utility of SMM in identifying patients with multicentric breast cancer. Breast cancer patients treated by mastectomy who underwent a preoperative SMM between 1992 and 1999 were identified using the institution's Tumor Registry. The pathology report of each patient was reviewed for multicentric disease defined as an additional focus of cancer within a different quadrant of the breast or greater than 2.5 cm from the dominant tumor mass. Each patient's preoperative SMM was reviewed and compared with the pathologic findings to obtain correlative data. Fifty-eight women treated by mastectomy had preoperative SMM (age range 35-78 years; median 52 years). Pathology revealed infiltrating ductal carcinoma in 49 patients (84.5%), infiltrating lobular carcinoma in five patients (8.6%), ductal carcinoma in situ in three patients (5.1%), and colloid carcinoma in one patient (1.7%). Multicentric disease was present in the specimens of eight patients for a prevalence of 10.3 per cent. SMM was positive for uptake in 36 of 58 patients (sensitivity 62.1%). The sensitivity, specificity, positive predictive value, and negative predictive value of SMM in the detection of multicentric disease were 62.5, 96, 71, and 94 per cent, respectively. Although the overall sensitivity of SMM in the detection of breast cancer is superior to that of conventional mammography and physical examination in identifying multicentric breast cancer it is not an accurate modality for detecting multicentric disease in this study group. However, it may have limited applications in specific cases.

Diagnostic accuracy of 99mTc-sestamibi breast imaging: multicenter trial results.

UNLABELLED: Although mammography is well established as a first-line tool for breast cancer screening and detection, efforts to develop complementary procedures continue. Observation of 99mTc-sestamibi tumor uptake provided the impetus for its evaluation as an adjunctive technique. This trial's objectives were to determine in a multicenter trial the diagnostic accuracy of 99mTc-sestamibi in women with suspected breast cancer and to investigate factors influencing diagnostic accuracy. METHODS: Our multicenter trial enrolled 673 women (387 with nonpalpable abnormalities; 286 with palpable abnormalities) scheduled for excisional biopsy or mastectomy. Blinded and unblinded interpretations of scintigraphic images were compared with core laboratory established histopathologic diagnoses to define the diagnostic accuracy of 99mTc-sestamibi breast imaging. RESULTS: Blinded readers' diagnostic accuracy was 78%-81%. Inter-reader agreement was excellent, ranging from 95% to 100% (kappa = 0.82-0.99). Overall institutional sensitivity and specificity for 99mTc-sestamibi breast imaging were 75.4% and 82.7%, respectively. In this population with a 40.1% disease prevalence, the positive predictive value was 74.5% and the negative predictive value was 83.4%. The negative predictive value was 94% in patients with a 40% or lower mammographic likelihood of breast cancer. Sensitivity was higher for palpable abnormalities; specificity was higher for nonpalpable abnormalities. Sensitivity was decreased for tumors <1 cm in largest dimension but appeared not to be affected by patient's age. CONCLUSION: As an adjunct to current procedures, 99mTc-sestamibi breast imaging may contribute to patient management decisions in selected populations, including women with dense breasts, mammographically indeterminate lesions >1 cm, and palpable abnormalities.

Status of scintimammography and its relationship to other detection methods for breast cancer.

Breast cancer is the most important malignancy for women of the world's industrialized nations. It is second only to lung cancer in cancer-related mortality. Early detection is the best means of improving survival; the cornerstone of early diagnosis is mammography. Given the endemic nature of breast cancer, screening mammography has secured a routine place in health maintenance for women, although it is less than perfect. To aid in the diagnosis of malignant breast disease, other imaging modalities have evolved: ultrasound, magnetic resonance imaging (MRI), positron emission tomography (PET), and SMM. Scintimammography (SMM) is rapidly with a variety of applications for the management of breast disease. This technology has become a complementary modality to other conventional methods of breast imaging. This review will focus on the science behind SMM and how it is currently used in the management of breast lesions.

Scintimammographic analysis of nonpalpable breast lesions previously identified by conventional mammography.

BACKGROUND: In randomized trials, screening mammography has led to decreased mortality from breast cancer. However, the low positive predictive value of mammography (i.e., the proportion of patients with a positive test result who actually have breast cancer) results in a large number of unnecessary biopsies. We determined whether scintimammography with technetium-99m-sestamibi is a useful supplemental diagnostic tool for women with nonpalpable breast abnormalities identified by conventional mammography. METHODS: Scintimammography was performed preoperatively on 70 women who were 31-66 years of age (mean age and median age = 51 years). These women had nonpalpable breast abnormalities identified by conventional mammography; subsequently, a needle-localization excisional biopsy of each suspicious lesion was performed. Scintimammographic images were interpreted independently by two nuclear medicine physicians who were blinded to all clinical and pathologic data, and an interobserver variation analysis was performed. RESULTS: Interobserver variation analysis of the scintimammographic findings showed an agreement for breast diagnosis of 97% and a kappa coefficient of 0.90. Comparison of scintimammographic findings and histopathologic results revealed that the sensitivity (proportion of patients with breast cancer who had a positive test result), the specificity (proportion of patients without breast cancer who had a negative test result), the positive predictive value and the negative predictive value (proportion of patients with a negative test result who actually did not have breast cancer) of scintimammography were 56% (95% confidence interval [CI] = 23%-85%), 87% (95% CI = 75%-94%), 38% (95% CI = 15%-68%), and 93% (95% CI = 82%-98%), respectively. Four of nine breast cancers were not detected by scintimammography. CONCLUSION: Because of excellent interobserver agreement, scintimammography provides an objective way of detecting primary breast carcinoma. In view of its low sensitivity and positive predictive value, however, scintimammography is not currently recommended as a screening test in patients with nonpalpable positive mammographic findings.

Technetium-99m-sestamibi scintimammography for the detection of breast carcinoma: comparison between planar and SPECT imaging.

UNLABELLED: The purpose of our study was to compare the results of planar and SPECT scintimammography for the detection of breast carcinoma. In addition, our goal was to determine whether SPECT reconstructed with filtered backprojection (FBP) or with iterative algorithms (ISA) can improve the sensitivity and specificity of planar scintimammography (SMM). METHODS: One hundred thirteen patients with suspicious physical examinations and/or mammography underwent planar lateral and anterior breast imaging as well as SPECT imaging after injection of 99mTc-sestamibi. We used a blind evaluation, both separately and combined, for planar SMM, ISA-SPECT and FBP-SPECT. Scintigraphic findings were correlated with the final histopathological diagnoses. RESULTS: The sensitivity of planar SMM was 80% with a specificity of 83%. All ISA-SPECT studies were of diagnostic quality, while FBP-SPECT was considered nondiagnostic in 14 that were excluded for statistical calculation. Sensitivity of ISA-SPECT and FBP-SPECT were 71% and 69%, respectively. Specificity was 70% for ISA-SPECT and 66% for FBP-SPECT. Combined planar SMM plus ISA-SPECT sensitivity was 85% (81% for planar SMM plus FBP-SPECT) with a specificity of 72%. Three carcinomas indeterminate on planar SMM were correctly identified by combined planar SMM plus ISA-SPECT. ISA-SPECT and FBP-SPECT provided additional information to planar SMM with respect to localization of sestamibi uptake, tumor extent, improved diagnostic certainty and detection of axillary nodes in 40 and 14 patients, respectively. CONCLUSION: ISA reconstruction is the preferable approach to SPECT data. Combined with planar SMM, ISA-SPECT can improve sensitivity. SPECT is useful in cases of indeterminate and positive planar SMM.

Immunohistologic assessment of technetium-99m-MIBI uptake in benign and malignant breast lesions.

UNLABELLED: This study was undertaken to assess the relationship between the degree of 99mTc-MIBI uptake in breast lesions and the following histologic factors: neovascularity, desmoplastic reaction, cellular proliferation and mitochondrial density. METHODS: Forty-two patients who previously underwent MIBI breast imaging (4 false-negative, 12 false-positive, 15 true-negative, 11 true-positive) were studied. Immunohistochemical staining was performed for neovascularity (Factor VIII antigen), desmoplasia (alpha-actin antigen), mitochondrial density (mitochondrial antigen) and cellular proliferation (MIB-1 antigen). The degree of microscopic staining was correlated with region of interest measurements of MIBI uptake on scintigraphy. RESULTS: There was a poor correlation between MIBI uptake and the degrees of neovascularity (r = 0.08, p > 0.05) and intracellular mitochondrial density (r = 0.04, p > 0.05) while there was a moderate correlation with cellular proliferation (r = 0.4, p < 0.05) and desmoplasia (r = 0.55, p < 0.001). CONCLUSION: The degree of MIBI uptake in breast lesions is multifactorial, but it appears to be related more to the degree of desmoplastic activity and cellular proliferation than neovascularity and mitochondrial density.

Limited value of scintimammography and contrast-enhanced MRI in the evaluation of microcalcification detected by mammography.

The aim of this study was to evaluate whether scintimammography using 99Tc(m)-sestamibi or contrast-enhanced magnetic resonance imaging (MRI) can improve the specificity of mammography for the differentiation of benign and malignant breast microcalcification. From 156 consecutive patients studied with SMM, 44 patients with microcalcification on mammograms were selected for this study. Forty patients in this group also had contrast-enhanced MRI of the breast. The intensity and patterns of sestamibi uptake for scintimammography and contrast enhancement for MRI were visually determined and graded on a 5-point scale for malignancy. The results of both techniques were compared and correlated with final histopathologic diagnoses. The sensitivity and specificity of scintimammography were 63% and 85% respectively, if only those cases classified as probable or definite malignancy were considered positive. If indeterminate findings were also considered positive, the sensitivity and specificity of scintimammography were 79% and 80% respectively. Using the latter classification for MRI revealed a comparable sensitivity of 82% but a markedly lower specificity of 56%. Excluding indeterminate findings from the group of positive MRI diagnoses resulted in a specificity of 94% and a sensitivity of 64%. In conclusion, scintimammography of the breast had a comparable sensitivity but a higher specificity than MRI. The sensitivity of both techniques, however, is probably too low for routine use in the evaluation of microcalcification detected by mammography.

Role of technetium-99m sestamibi scintimammography and contrast-enhanced magnetic resonance imaging for the evaluation of indeterminate mammograms.

This study evaluated and compared technetium-99m sestamibi scintimammography (SMM) and breast magnetic resonance imaging (MRI) results in patients with indeterminate mammograms to determine whether either technique can improve the sensitivity and specificity for the diagnosis of breast carcinoma. From 123 consecutive patients who underwent physical examination, mammography, SMM, and histopathologic confirmation, a subgroup of 82 patients presenting with indeterminate mammograms was studied. Sixty-eight patients underwent contrast-enhanced MRI. SMM results were scored on the basis of the intensity and pattern of sestamibi uptake. MRI images were scored on the basis of signal intensity increase after administration of contrast material as well as the enhancement pattern and speed of gadolinium uptake. The results obtained with the two techniques were compared and related to the final histopathologic diagnoses. Considering indeterminate findings as positive, the sensitivity of SMM was 79% and the specificity, 70%. MRI displayed a sensitivity of 84% and a specificity of 49%. When indeterminate results were considered negative, the sensitivity and specificity of SMM were 62% and 83%, respectively. MRI revealed a sensitivity and specificity of 56% and 79%, respectively. The calculated sensitivities and specificities demonstrate the diagnostic limitations of both SMM and MRI in the evaluation of patients with indeterminate mammographic findings. Due to the higher specificity, SMM may be the preferred modality in the evaluation of selected patients with breast abnormalities.

Detection of axillary lymph node metastasis of breast carcinoma with technetium-99m sestamibi scintimammography.

Several investigators have advocated management of breast cancer patients without axillary dissection, obviating the morbidity associated with this procedure. Approximately 30-40 per cent of all patients with breast carcinoma will have lymph node metastasis. Axillary dissection offers no therapeutic benefit to node-negative patients, and it may lead to unnecessary morbidity. It is apparent that a noninvasive test to determine the presence of axillary metastases may obviate the need for axillary dissection. The aim of this study was to determine the role of scintimammography (SMM) with technetium-99m sestamibi in the detection of axillary node metastasis in breast carcinoma. Thirty-one women with the diagnosis of breast carcinoma who had SMM and axillary lymphadenectomy were included. SMM was done following an intravenous injection of 20 mCi of Tc-99m sestamibi. Planar scintigraphic imaging was acquired in a lateral prone and an anterior view of the breasts for the evaluation of the axilla. SMM scans were interpreted by two nuclear medicine physicians blinded to the clinical presentation and histologic results. The correlation of SMM with histologic assessment showed a sensitivity of 75 per cent, specificity of 82 per cent, positive predictive value of 88 per cent, and negative predictive value of 64 per cent. The interobserver correlation of SMM interpretation between the two nuclear medicine physicians showed good agreement, with kappa = 0.49. Consistency in the interpretation of Tc-99m SMM was obtained when two independent radiologists reviewed the studies. Based on these data, we are unable to show that SMM is a reliable test for the detection of axillary metastases in patients with breast cancer. However, a high positive value of 88 per cent is encouraging and deserves further study.

Scintimammography: the new role of technetium-99m Sestamibi imaging for the diagnosis of breast carcinoma.

Technetium-99-Sestamibi scintimammography has emerged as a new procedure for the imaging of breast tumors. Currently, a large clinical experience has been developed and the results published. At the present time, the major drawback of this procedure appears to be its low sensitivity for the detection of breast carcinomas smaller than 1 cm in diameter. There are other biologic and technical issues that remain to be overcome to optimally image the breasts. Some of these include: development of a dedicated breast imager using nuclear medicine techniques, development of stereotactic needle localization of the abnormalities that demonstrate focal increase uptake in women with normal mammogram and breast physical examination, manufacturing of a breast compression device so that we can immobilize the breast in place for more adequate imaging, overcoming the issue of unilateral or bilateral diffuse breast uptake that is noted in 7-10 percent of the cases and finally, determination of optimal dose and imaging factors. This review includes our experience at Harbor-University of California, Los Angeles Medical Center with the use of this agent for breast imaging since 1992.

Radionuclide-guided stereotactic prebiopsy localization of nonpalpable breast lesions with normal mammograms.

UNLABELLED: Scintimammography with 99mTc-sestamibi can be used as a complementary technique to improve the mammogram's sensitivity and specificity for detection of breast carcinoma. We have observed in some patients focal areas of increased 99mTc-sestamibi uptake with no corresponding abnormalities on physical examination or mammogram. A phantom device and a special needle were designed to stereotactically localize these lesions before biopsy. METHODS: After intravenous injection of 30 mCI (1110 MBq) of 99m Tc-sestamibi, a prone lateral image of the abnormal breast was obtained. With the patient in the prone position, the breast was compressed with two fenestrated plates in the prone position. The x and y coordinates of the abnormal hot spot of the breast were determined. The z coordinate of focal 99mTc-sestamibi uptake was determined by advancing a localizer needle through a selected predetermined hole of the fenestrated plate using real-time visualization on the persistence monitor. The tip of the opturator inside the needle is welded with 57Co to determine the depth of the hot spot in the breast. RESULTS: Three women, all of whom had normal mammogram and breast physical examinations, were studied using 99mTc-sestamibi prone breast imaging. Pre-excisional biopsy needle localization of abnormal focal uptake was performed. Two women demonstrated infiltrative ductal carcinoma, and the third had proliferative fibrocystic disease of the breast. CONCLUSION: Our initial experience demonstrates that nuclear medicine guided stereotactic needle biopsy of the breast in patients with positive scintimammograms is technically feasible. In the future, this technology will enable us to detect breast carcinoma in the absence of clear-cut clinical and mammographic findings.

Breast Cancer Imaging: Can Tc-99m Sestamibi Scintimammography Fit In?

Mammography and physical examination are currently the most frequently used screening tests for breast cancer. Considering the 85% sensitivity associated with combined mammography and physical examination and a low positive predictive value of 20% to 30% for the diagnosis of breast carcinoma, there is a critical need for a more accurate noninvasive imaging test to improve the sensitivity and specificity of mammography. This study evaluates the role of Tc-99m sestamibi scintimammography as a complementary procedure to conventional mammography for the detection of breast carcinoma. A sample of 157 women (mean age 47.9 years +/- 10.2 years) with 164 lesions appropriate for histologic and cytologic analysis on the basis of suspicious findings on a mammogram and/or physical examination underwent scintimammography. Subsequently, excisional biopsy and/or fine-needle aspiration were performed. There were 52 primary cancers (8 different histopathologic types) and 112 benign breast lesions (6 different histopathologic types). The sensitivity of Tc-99m sestamibi scintimammography for detecting primary breast cancer was 92.3%, and its specificity was 87.5%. Percent-positive and -negative predictive values associated with Tc-99m sestamibi scintimammography in this cohort were 77.4% and 96.0%, respectively.

Scintimammography with Tc-99m sestamibi.

Mammography and physical breast examination are currently the most frequently and recognized screening tools for detection of breast carcinoma. These methods have been proved successful for early detection of breast cancer. Considering the 85% sensitivity associated with combined mammography and physical examination and a low positive predictive value of 20%-30% for diagnosis of breast carcinoma, there is a critical need for a more accurate, noninvasive imaging test to improve the sensitivity and specificity of mammography (7, 19, 20). Since early 1992, we have studied over 1200 women with clinically and/or mammographic abnormalities prior to breast biopsy and/or fine needle aspiration cytology of the breast. We have evaluated the role of Tc 99m Sestamibi as a complimentary procedure to conventional mammography in detection of breast carcinoma. The preliminary results of our studies have been published elsewhere (14, 17, 18). DuPont Merck Pharmaceutical Company in the USA on that basis, determined to conduct a multicenter clinical trial for the role of this radiopharmaceutical for the diagnosis of breast carcinoma in women with mammographically and/or clinically palpable abnormalities. This study was conducted at 42 institutions throughout the United States and Canada enrolling 673 women who where otherwise scheduled for breast biopsy and/or mastectomy. The preliminary results of this trial in both palpable and nonpalpable breast abnormalities are encouraging (24). Our most recent study on 157 women (mean age 47.9 years +/- 10.2) with 164 lesions with indications for histologic and cytologic analysis who underwent scintimammography with Tc 99m Sestamibi demonstrated the sensitivity of 92.3% and the specificity 87.5% (15). We have concluded that Scintimammography with Tc 99m Sestamibi can be used in conjunction with mammography to improve its specificity.