Medicine Section - Electrical Impedance Scanning of the Breast

IMPORTANT REMINDER

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Description

Electrical impedance scanning of the breast involves the transmission of continuous electricity into the body using either an electrical patch attached to the arm or a hand-held cylinder. The electrical current travels through the breast where it is then measured at skin level by a probe placed on the breast. Cancerous tissue conducts electricity differently than normal tissue; therefore, cancerous images may show up on the resulting imaging as a bright white spot. The T-Scan™ 2000 is an electrical impedance scanning device that received approval for marketing from the U.S. Food and Drug Administration (FDA) in 1999, with the following labeled indication: "The T-Scan™ 2000 is intended for use as an adjunct to mammography in patients who have equivocal mammographic finding with ACR Bi-RADS™ categories 3 or 4. In particular, it is not intended for use in cases with clear mammographic or non-mammographic indications for biopsy. This device provides the radiologist with additional information to guide a biopsy recommendation."

Research is underway on combining electrical impedance scanning with mammography or tomosynthesis. The use of electrical impedance scanning to diagnose non-malignant breast disease has also been studied, but apparently not with an FDA-approved device. The research used a multifrequency electrical impedance tomography device called MEM developed at the Russian Academy of Sciences; it has not received FDA approval.

Mammographic abnormalities can be stratified into categories called Bi-RADS™ (Breast Imaging Reporting Data System), which reflect the risk of malignancy given the mammographic appearance. Scores range from 1 to 5 as follows:

Electrical impedance studies are used as an adjunct to mammography to improve patient selection for biopsy in patients with equivocal indications, i.e., those designated as a Bi-RADS™ category 3 or 4. There are two potential scenarios:

Policy/Criteria

Electrical impedance scanning of the breast is considered investigational.

Scientific Background

The T-Scan™ 2000 was FDA approved through the PMA process, and thus the clinical data to support its safety and effectiveness are available in the FDA summary of safety and effectiveness which is reviewed below.  (2)  The key pieces of data presented to the FDA were from a multicenter blinded study that intended to test the hypothesis that adjunctive combination of T-Scan™ with mammography can provide diagnostic accuracy significantly better than mammography alone.

The results of this study were reported in terms of sensitivity and specificity instead of positive and negative predictive value. The blinded study presented to the FDA consisted of a total of 2,456 patients of whom 882 underwent biopsy and T-Scan™. The mammography and T-Scan™ were performed in a blinded fashion; i.e., each imaging procedure was performed and interpreted without knowledge of the results from any other imaging modality or patient information. A final test set composed of 504 biopsied breasts (179 malignant, 325 benign) was available for re-reading (380 patients were excluded due to unavailability of the original mammogram or incomplete T-Scan™ image). The test set was re-read and scored "blindly" using T-Scan™ images alone, using mammograms alone, and using adjunctive combination of mammogram and T-Scan™ images. Each of the scores was compared against the results of biopsy. Panels of 40–60 patients each were organized for blinded rereading of the T-Scan™s and mammograms. The panels were composed of patients with both malignant and benign biopsy results, as well as screening patients that did not undergo biopsy.

The screening patients were added to the panels so that the readers could not assume that all patients had suspicious mammographic findings. The key subgroup was the 273 patients with equivocal mammographic abnormalities. These included Bi-RADS™ 3 and some Bi-RADS™ 4 cases, in which the probability of malignancy was estimated to be between 0 and 50%. Using biopsy results as the gold standard, the sensitivity of the combined mammogram and T-Scan™ compared to mammogram alone increased from 60% to 82%, while the specificity increased from 41% to 57%. Both of these are statistically significant increases. However, it is unclear from this study if these diagnostic parameters would enable patients with equivocal mammographic abnormalities to forego biopsy. Recalculating the data reveals that the key parameter of the negative predictive value of the combined test is 93%. Therefore, if the decision to forego biopsy was based on a negative result of the combined mammogram and T-Scan™, 7% of those with malignant lesions would miss or delay a diagnosis of breast cancer.

As noted, this study included some Bi-RADS™ 3 or 4 lesions, but it is not specified whether the biopsies were performed in these subjects as part of the study protocol or based on clinical suspicion and/or imaging results. The analysis of diagnostic performance included only those patients who were scheduled for biopsy, which introduces the potential for verification bias. It is uncertain whether these selected cases would be similar to unselected consecutive cases of Bi-RADS™ 3 or 4 lesions that would not be referred for biopsy in clinical practice. The positive predictive value of adjunctive use of the T-Scan™ was reported to be 30% among biopsied subjects with Bi-RADS™ 3 or 4 lesions and an 18% prevalence of malignancy. However, the limitations and potential bias in this analysis prohibit conclusions regarding the effectiveness of using the T-Scan™ in positively selecting patients for biopsy. For example, it is unknown how many of the original 2,456 patients had equivocal lesions and decided to forego biopsy. This is the critical group to evaluate the role of the T-Scan™ to positively select those patients for biopsy who would otherwise forego biopsy. While this unselected population and outcome are admittedly more difficult to study, ideally one would like to design a trial in which all patients with equivocal lesions, which would otherwise be referred for follow-up imaging, undergo both T-Scan™ and biopsy or some other appropriate reference standard such as prolonged clinical follow-up. In this setting, the diagnostic performance and predictive value of T-Scan™ could be evaluated in the actual intended use.

The "Intended Use" study presented to the FDA consisted of 74 consecutive biopsy cases in which the T-Scan™ was approved for clinical use in its full intended mode; i.e., the T-Scan™ was targeted at lesions previously identified by mammography or physical examination, and the T-Scan™ interpretation was done adjunctively. Of these, there were a total of 36 cases for which biopsy results, mammograms, and T-Scan™s were available and where the mammographic results were equivocal. The sensitivity of the mammography alone was 66.7% increasing to 93.3% (28 of 30 cases) when the T-Scan™ was used adjunctively. The corresponding values of specificity were 50% increasing to 83.3% (5 of 6 cases) when the T-Scan™ was added. The positive predictive value of adjunctive use of T-Scan™ was 97% (28 of 29 cases) although the prevalence of malignancy in this subgroup was also very high at 83%. Despite these positive findings, the small number of cases in this study along with the potential bias associated with the fact that analysis was restricted only to half of subjects who received the reference standard makes this evidence insufficient to draw conclusions.

An updated search of the MEDLINE database through May 15, 2009 identified a variety of case series. Some studies focused on the technical capability of electrical impedance scanning. (3,4) All of those studies that reported on the diagnostic performance of electrical impedance scanning, reported an inferior performance to that reported in the FDA Summary of Safety and Effectiveness. (5-8)

Fuchsjaeger and colleagues further explored the adjunctive role of impedance scanning in 121 patients with 128 BI-RADS™  4 lesions identified on mammography. (9) Specifically, the results of impedance imaging were compared with ultrasound as a technique of further classifying benign lesions such that patients could be managed as a BI-RADS™ 3 lesion with a recommended six month follow up instead of biopsy.  Therefore, the key statistic is the negative predictive value to deselect patients for biopsy.  Based on histopathology from a subsequent biopsy, there were 37 malignant lesions and 91 benign lesions.  The negative predictive value of impedance imaging was 97.1% vs. 92.0% for ultrasound.  It is unclear whether this diagnostic performance would be adequate to defer biopsy.

Stojadinovic and colleagues explored the role for impedance scanning as a primary screening technique in younger women, defined as younger than 40 years of age, with average risk for breast cancer. (10) Currently there are no specific screening recommendations in this population due in part to decreased sensitivity of mammography in dense breast tissue, common in younger women.  The electrical conductivity in electrical impedance scanning may also be impacted by breast density.  This study included 1103 women who were undergoing screening with a clinical breast examination and women who were specifically referred for breast biopsy (the reasons for the referral were not stated).  Of the 580 women who were under 40 years of age, the targeted age group, 132 (23%) presented with palpable breast lesions.  Six cancers were identified, two of which were nonpalpable.  All cancers were found in women who had been referred for breast biopsy as compared with none found in the general screening population.  Sensitivity and specificity of impedance scanning in women under 40 was 50% and 90%, respectively.  As noted by the authors this is a preliminary study and further studies are needed.

In August 2006 the Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee discussed the pre-market approval application from Mirabel Medical Systems, Inc. (Austin, TX) for the T-Scan™ 2000 ED. (11) This device has been proposed as an adjunct to clinical breast examination for pre-screening asymptomatic women aged 30-39 at average risk for breast cancer who might have an increased risk of breast cancer and therefore be considered for further diagnostic study by analyzing differences in electrical impedance of breast tissue. The panel noted issues of concern regarding device sensitivity (26.4%), the size and population of the study, number of cancers detected in study patients, and risks associated with additional screening events.  The panel unanimously recommended that the PMA be found “not approvable”.  This device was used by Stojadinovic and colleagues in a two-arm, prospective, observational study of women aged 30-45 years. (12) The specificity arm included 1361 asymptomatic women. The sensitivity arm included 189 women with suspicious breast abnormality based on results of a prior clinical breast examination, mammography, ultrasound and/or MRI, and had been referred for breast biopsy. These women were tested with electrical impedance scanning immediately prior to undergoing the biopsy procedure. Specificity was 95% and sensitivity was again low at 38%.

In a later follow-up, Stojadinivoc and colleagues reported on 1,751 patients in the specificity group and 390 patients (with 87 cancers) in the sensitivity group. (13) The specificity calculated for the first group (assuming all positive test results were incorrect) was 94.7% (95% CI: 93.7–95.7%). One center had a specificity of 84%, while the others ranged from 89% to 97%. Sensitivity calculated for the second group was 26.4% (95% CI: 17.4–35.4%). The number of cancers at each site was small; the sensitivity per site ranged from 0% to 53%. Combining these results and the assumption that the prevalence of breast cancer in an average-risk group of women 30-39 years of age, the authors estimated that for every 136 women with a positive T-scan result, one would have cancer. If all T-scan-positive women in this age group underwent mammography, it is estimated that about 1 in 194 women would have cancer (this estimate is lower because of the less than perfect sensitivity of mammography). The authors stated that this detection rate is higher than would be found among a randomly selected group of 30- to 39-year-old women or among women younger than 40 years of age with an affected first-degree relative (about one cancer detected in every 333 women). The relative probability of cancer in a T-Scan-positive woman is estimated to be 4.95 (95% CI: 3.16–7.14). These calculations apparently did not include the patients in whom T-Scans were attempted but not completed: 14 women in the specificity group and four women in the sensitivity group. Sixty-six results in the second group were considered unreliable because of technical difficulties, but the authors argue that these problems might have been corrected if the examiners had not been blinded to the results and, therefore, were unaware of the problems; examiners in the specificity group were not blinded. The sensitivity of this test remains low, even in a group of women with a deliberately higher prevalence of cancer than would be expected in a screening population.

Further research has also been performed on the characteristics of electromagnetic breast imaging in distinguishing between normal breast tissue and abnormal tissue, and between cancerous and benign abnormal tissue. (14) EIS was one of three electromagnetic imaging modalities used in women with mammography results rated as Breast Imaging Reporting and Data System (BI-RADS) “normal” category 1 (n=53) or “abnormal” categories 4 (suspicious for malignancy) or 5 (highly suspicious for malignancy) (n=97). The focus was on a prospective, quantitative assessment of the contrast in electromagnetic properties between normal and abnormal tissue. EIS results were available for 62 “abnormal” cases and 36 normal controls; EIS data were not available for 19 cases due to technical difficulties and 33 cases due to analytical difficulties (data calibration). EIS was found to help in discrimination between normal and abnormal tissue but “may not aid” in distinguishing between cancer and other abnormal pathological findings. Using results from all three modalities examined (EIS, microwave imaging spectroscopy, and near-infrared spectral tomography) did not substantially improve the ability to identify breast cancer.

References

1. BlueCross and BlueShield Association Medical Policy reference Manual, Policy No. 2.01.63
2. www.fda.gov/cdrh/pdf/p970033b.pdf (Verified 5/15/09)
3. Perlet C, Kessler M, Lenington S et al. Electrical impedance measurement of the breast: effect of hormonal changes associated with the menstrual cycle. Eur Radiol 2000;10(10):1550-4
4. Martin G, Martin R, Brieva MJ et al. Electrical impedance scanning in breast cancer imaging: correlation with mammographic and histologic diagnosis. Eur Radiol 2002;12(6):1471-8
5. Malich A, Bohm T, Facius M et al. Additional value of electrical impedance scanning: experience of 240 histologically proven breast lesions. Eur J Cancer 2001;37(18):2324-30
6. Wersebe A, Siegmann K, Krainick U et al. Diagnostic potential of targeted electrical impedance scanning in classifying suspicious breast lesions. Invest Radiol 2002;37(2):65-72
7. Malich A, Boehm T, Facius M et al. Differentiation of mammographically suspicious lesions: evaluation of breast ultrasound, MRI mammography and electrical impedance scanning as adjunctive technologies in breast cancer detection. Clin Radiol 2001;56(4):278-83
8. Malich A, Fritsch T, Anderson R et al. Electrical impedance scanning for classifying suspicious breast lesions: first results. Eur Radiol 2000;10(10):1555-61
9. Fuchsjaeger MH, Flory D, Reiner CS, et al. The negative predictive value of electrical impedance scanning in BI-RADS category IV breast lesions. Invest Radiol. 2005;40(7):478-85
10. Stojadinovic A, Nissan A, Gallimidi Z, et al. Electrical impedance scanning for the early detection of breast cancer in young women: preliminary results of a multicenter prospective clinical trial. J Clin Oncol. 2005;23(12):2703-15
11. Obstetric and Gynecology Devices Panel August 29, 2006 (Summary) www.fda.gov/cdrh/meetings/082906-summary.html  (Verified 5/15/09)
12. Stojadinovic A, Moskovitz O, Gallimidi Z, et al. Prospective Study of Electrical Impedance Scanning for Identifying Young Women at Risk for Breast Cancer. Breast Cancer Res Treat 2006 May;97(2):179-89
13. Stojadinovic A, Nissan A, Shriver CD et al. Electrical impedance scanning as a new breast cancer risk stratification tool for young women. J Surg Oncol 2008;97(2):112-20
14. Poplack SP, Tosteson TD, Wells WA et al. Electromagnetic breast imaging: results of a pilot study in women with abnormal mammograms. Radiology 2007;243(2):350-9

Cross References

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