The Problem of Mammographic Breast Density - The Position of the DEGUM Working Group on Breast Ultrasound.

Mammographic breast density correlates with breast cancer risk and also with the number of false-negative calls. In the USA these facts lead to the "Breast Density and Mammography Reporting Act" of 2011. In the case of mammographically dense breasts, the Working Group on Breast Ultrasound in Germany recommends explaining the advantages of adjunct imaging to women, depending on the individual breast cancer risk. Due to the particular structure of German healthcare, quality-assured breast ultrasound would be the first choice. Possible overdiagnosis, costs, potentially increased emotional stress should be addressed. In high familial breast cancer risk, genetic counselling and an intensified early detection program should be performed.

[Evaluation of the nationwide DEGUM breast ultrasound training program]. / Evaluation der DEGUM-Mammasonografiekurse nach objektivierbaren Kriterien.

PURPOSE: The aim of this study was to evaluate the quality standard of the nationwide breast ultrasound training program of the German Society of Ultrasound in Medicine (DEGUM) through objective parameters. MATERIALS AND METHODS: 10 quality criteria, based on the recommendations of The National Association of Statutory Health Insurance Physicians (KBV), were defined for this study. All training units of the DEGUM received a questionnaire. The questionnaires and training material were analyzed. RESULTS: All units met the required criteria pertaining to the trainer's qualification, duration per training course and the maximum number of participants per ultrasound machine. Only 1 course did not fulfill the required 50 % practical training time. The requirements to participate in the graduate course (200 self-made and documented cases) were not clearly conceived and a defined training log could be improved. CONCLUSION: DEGUM breast ultrasound training offers trainees a high level of education based on the requirements of the KBV. Despite the high quality of training, the content of course announcements could be improved and an official and structured educational index could be meaningful.

ShearWave™ Elastography BE1 multinational breast study: additional SWE™ features support potential to downgrade BI-RADS®-3 lesions.

PURPOSE: To determine the benefit of ShearWave™ Elastography (SWE™) in the ultrasound characterization of BI-RADS® 3 breast lesions in a diagnostic population. MATERIALS AND METHODS: 303 BI-RADS® 3 lesions (mean size: 13.2 mm, SD: 7.5 mm) from the multicenter BE1 prospective study population were analyzed: 201 (66%) had cytology or core biopsy, and the remaining 102 had a minimum follow-up of one year; 8 (2.6%) were malignant. 7 SWE features were evaluated with regard to their ability to downgrade benign BI-RADS® 3 masses. The performance of each SWE feature was assessed by evaluating the number of lesions correctly reclassified and the impact on cancer rates within the new BI-RADS® 3' lesion group. RESULTS: No malignancies were found with an E-color "black to dark blue", which allowed the downgrading of 110/303 benign masses (p < 0.0001), with a non-significant increase in BI-RADS® 3' malignancy rate from 2.6% to 4.1%. E-max ≤ 20 kPa (2.6 m/s) was able to downgrade 48/303 (p < 0.0001) lesions with a lower increase in BI-RADS® 3' malignancy rate (3.1%). No other SWE features were useful for reclassifying benign BI-RADS® 3 lesions. CONCLUSION: Applying simple reclassification rules, SWE assessment of the maximum stiffness of lesions allowed the downgrading of a sub-group of benign BI-RADS® 3 lesions. This was accompanied by a non-significant increase in the malignancy rate in the new BI-RADS® 3 class.

Multivariate analysis of flow data in breast lesions and validation in a normal clinical setting.

PURPOSE: To improve differentiation between benign and malignant breast lesions by Doppler measurements and to validate results in a normal clinical setting in comparison to study conditions. MATERIALS AND METHODS: Doppler measurements of 458 patients were compared in benign and malignant tumors in a prospective study. In a multivariate analysis a diagnostic score was developed using a logistic regression model and stepwise selection. These results were compared with 272 patients who were examined under routine clinical conditions. RESULTS: Most measurements showed highly significant (p < 0.001) differences between benign and malignant tumors. For each measurement we considered two cut-points to define a diagnostic rule. Despite significant differences, none of the corresponding classification rules exceeded 90 % sensitivity and specificity. Multivariate analysis selected a model including age and the number of arteries and contralateral arteries. Although significant, the last factor barely improved diagnostic accuracy. Therefore, we deleted it from the multivariate model. Based on a simple model including age and the number of tumor arteries, we defined classification rules with high sensitivity and specificity. The RI measurement did not improve the discriminatory power of our score. In the validation study the sensitivity decreased from 89 - 98 % to 58 - 78 % with a specificity of 82 - 92 % vs. 83 - 86 %. CONCLUSION: Color Doppler can be used for breast cancer differentiation. However, in the clinical routine the sensitivity decreases considerably compared with optimized study conditions.

[Impact of breast ultrasound screening in gynecological practice]. / Bedeutung der Mammasonografie für die Brustkrebsfrüherkennung in der gynäkologischen Praxis.

PURPOSE: To define the value of whole breast ultrasound for breast cancer detection in primary women's health care in gynecological routing practice. MATERIALS AND METHODS: Among women who were operated at the breast center of the German Diagnostic Clinic (DKD) in the year 2007, we selected different indications for the examinations which were relevant for the detection of breast lesions. RESULTS: Twenty-one of 86 breast cancers (24 %) which were treated at the DKD in the year 2007 were detected only because of an individual ultrasound screening examination. None of these women had abnormal clinical findings and only 8 of these women had abnormal mammograms. The majority of these cancers were early stages, pT1a/b. In this group of patients, only 8 benign lesions detected by ultrasound were operated. This corresponds to a ratio of benign vs. malignant operations of 0.4 to 1, which is far superior to the recommendations of international guidelines for quality assurance. CONCLUSION: Our results show that ultrasound screening considerably increases the detection of early breast cancers without increasing the rate of unnecessary biopsies. This should encourage gynecologists to learn and perform systematic breast ultrasound examinations and to increase their own performance by continuous training. We can expect that additional studies will prove breast ultrasound to be a powerful method for improving breast cancer detection. Currently available state-of-the-art ultrasound technology allows for early detection, but further education and quality control are important for implementation in nation-wide health care.

Sonographic criteria for the confirmation of implant rotation and the development of an implant-capsule-interaction ("interface") in anatomically formed textured breast implants with texturised Biocell-surface.

AIM: In comparison to round breast implants, anatomically formed implants have a broader indication spectrum in augmentation surgery for the formation of a natural breast shape. In order to achieve a long-term result, it is necessary for anatomically formed breast implants to remain secured in the position desired and planned initially. In the case of textured implants of a certain pore size and depth, this can be aided by the development of a stabilising implant-capsule-interaction (interface). The aim of this study was to investigate whether there are sonographic criteria for verifying the position of anatomically formed breast implants and the development of a stable interface. MATERIAL AND METHODS: 628 patients underwent breast implant surgery and were followed up clinically as well as sonographically at the Frauenklinik und Institut für Asthetische Chirugie am St. Josefs-Hospital, Wiesbaden. 228 implants (Style 410 Inamed McGhain) were evaluated after a mean of 27 months postoperatively. Only cosmetic augmentations were included in the results. Verification of the implant position was conducted by palpation as well as by sonography. Statistical analysis was performed using the McNemar-Test (Chi-squared test). RESULTS: Two marker points on the anterior side of the implant capsule in the lower hemisphere, which are designed for intraoperative position monitoring by palpation, could be reproduced sonographically in all cases and the position of the breast implant could thereby by determined. Two cases of clinically apparent implant rotation of more than 90 degrees around the vertical axis were discovered in this way. The sonographical identification of the development of a stable interface between the implant and the periprosthetic capsule is possible when sonographic criteria of the "parasternal movement layer" are met. The sonographic outcome is significantly superior to palpation. CONCLUSION: Breast sonography used for the clinical follow-up of patients with anatomically formed breast implants represents an efficient diagnostic supplement with clinical relevance.

Likelihood of malignancy in breast lesions characterised by ultrasound with a combined diagnostic score.

To determine the positive predictive value of breast ultrasound (US) categories and US features, isolated and in combination, 398 consecutive sonographically diagnosed breast tumours with histologic or cytologic diagnosis were reviewed. Tumour characterisation and the sonographer's diagnoses were recorded prospectively using the diagnostic classification of the European Society of Mastology (EUSOMA) (U2 = probably benign lesion, U3 = an abnormality present of indeterminate significance, U4 = features suspicious of malignancy). In addition, based on the likelihood of malignancy of each US characteristic, a diagnostic score was developed. These two measures were compared. US-guided biopsy revealed 338 benign and 60 (55 invasive and 5 noninvasive) malignant lesions. EUSOMA and diagnostic score classifications did not differ significantly. If all breast tumours classified U3 and U4 were to be tested, every second biopsy (48.3%) would have revealed a carcinoma with a negative predictive value of 99.3%. The frequency of carcinoma in sonographically benign lesions (U2 or score 1) was 0.7 and 2.2%, respectively, an incidence similar to that with mammographic lesions classified as BI-RADS 3 (Breast Imaging Reporting and Data System, probably benign, short interval follow-up suggested). Thus, given that clinical symptoms and real-time imaging influence the sonographer's interpretation, the proposed diagnostic score can improve the diagnostic accuracy of the breast sonogram with the result of reducing invasive testing and maintaining a high detection rate.

[Advantages and limitations of breast ultrasound]. / Vorteile und Grenzen der Brust-Ultraschalldiagnostik.

Technological improvements in image quality have allowed to expand the indications for the use of breast ultrasound. This includes tumor differentiation, peroperative staging, follow-up after cancer treatment and interventional diagnosis. Up to now, only mammography has been useful for population-based screening. However, high-resolution and quality-controlled ultrasound can further improve early cancer detection. This is useful in high-risk patients and women with dense breasts who are mammographically problematic. The population-wide use of this advanced indication for breast ultrasound depends on equipment quality and investigator experience. Up to now, there has been a lack of guidelines and regulations. The implementation of quality control is essential before high-quality and effective breast ultrasound can be generally offered.

Value of sonomorphological criteria of the endometrium in women with postmenopausal bleeding: a multivariate analysis.

OBJECTIVE: This study was performed to examine whether an improvement in the transvaginal sonographic evaluation of the endometrium is possible by the addition of sonomorphological criteria to the measurement of endometrial thickness in women with postmenopausal bleeding. METHODS: Various sonomorphological criteria were analyzed prospectively in 321 patients with postmenopausal bleeding. In a logistic regression model relevant criteria were selected and a diagnostic formula for differentiation of endometrial sonographic findings was derived. RESULTS: The criteria of endometrial structure, endometrial-myometrial border and endometrial thickness were significant for the differentiation of malignancy. These results allowed an estimation of the probability of malignancy for each sonographic endometrial finding. Using the cut-off point of 0.1 for the probability of malignancy, the sensitivity and specificity were 96.8% and 61.9%, respectively, with an accuracy of 72.3%. In contrast, the differentiation by endometrial thickness as the sole criterion (cut-off point > or = 5 mm) achieved a sensitivity of 97.9% and a specificity of 33.2%, with an accuracy of 52.3%. CONCLUSION: A useful diagnostic formula based on sonomorphological and metric criteria for endometrial differentiation was obtained. The specificity and accuracy increased with a minimal loss of sensitivity. However, estimates for sensitivity, specificity, and accuracy may be overoptimistic because they were derived from the same data used for development of the model.

A new Doppler signal enhancing agent for flow assessment in breast lesions.

OBJECTIVE: To determine the diagnostic performance of SonoVue (Bracco) in the enhancement of Doppler signals in breast lesions and in the improvement of diagnostic accuracy. METHODS: This multicenter study included 220 patients undergoing investigations of parenchymal lesions, 40 of which had breast tumors. After a baseline Doppler examination, intravenous doses of 0.3, 0.6, 1.2 and 2.4 ml SonoVue were injected. Doppler signal quality before and after injection was compared. Off-site assessment of the global quality of Doppler signal and duration of clinical useful enhancement, as well as off-site and on-site evaluation of quality of color and spectral Doppler, were performed. On-site evaluation of diagnostic accuracy was also carried out. Safety assessments included monitoring of adverse events up to 24 h following the last injection of SonoVue. RESULTS: On-site evaluations: baseline Doppler was conclusive in only 4/21 carcinomas and in 2/17 benign lesions. Enhanced Doppler improved differential diagnosis in 20/21 carcinomas and in 9/12 benign lesions. Time to color enhancement was 0.55 min for the lowest and 0.35 min for the highest dose. The total duration of enhancement was 3.47 min for the lowest and 5.62 min for the highest dose, respectively. Off-site assessment: SonoVue improved the quality of Doppler blood flow information both in parenchymal and focal lesions. Statistically significant changes from baseline in global quality of Doppler investigations were observed at all four SonoVue doses (P<0.05). The duration of clinically useful signal enhancement increased with doses and a significant dose relationship was obtained (P<0.001). Mild adverse events were observed in two patients only. CONCLUSION: The results obtained from this study, following both off-site and on-site assessment, demonstrate that the administration of SonoVue to patients with focal breast lesions provides significant improvement over the baseline of Doppler signal quality and a clinically useful duration of signal enhancement, related to the dose. SonoVue was shown to be a safe and well-tolerated compound.

Effects of PTK787/ZK 222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model.

Antiangiogenic therapy is a promising new strategy to inhibit tumor growth and formation of metastases. Vascular endothelial growth factor (VEGF) and its receptors, VEGF-receptor 1 (VEGF-R1; FLT-1) and VEGF-R2 (KDR), have been shown to play a major role in tumor angiogenesis. PTK787/ZK 222584, a specific inhibitor of both VEGF-receptor tyrosine kinases, was investigated for its antitumoral and antiangiogenic activity in a murine renal cell carcinoma model. After intrarenal application of the renal carcinoma cells, mice develop a primary tumor and metastases to the lung and to the abdominal lymph nodes. Daily oral therapy with PTK787/ZK 222584 at a dose of 50 mg/kg resulted in a significant decrease of 61 and 67% in primary tumors after 14 and 21 days, respectively. The occurrence of lung metastases was significantly inhibited at both time points (98% reduction and 78% reduction, respectively). After 14 days, no lymph node metastases developed in the PTK787/ZK 222584-treated group, whereas after 21 days of treatment, the lymph node metastases were reduced by 87%. Vessel density in tumor tissues, detected by immunohistochemistry with an anti-CD31 antibody, was significantly decreased by PTK787/ZK 222584. Using color Doppler imaging ultrasound, significant changes in blood flow in the tumor feeding renal artery were found under treatment with PTK787/ZK 222584. Blood flow changes correlated with changes in vessel density but not with tumor volume. The compound was well tolerated in all in vivo experiments and had no significant effects on body weight or general well-being of the animals. This was in contrast to the animals treated with the antiangiogenic agent TNP-470. s.c. therapy with 30 mg/kg TNP-470 every other day had to be discontinued after 13 days because of animal weight loss (>20%) and ataxia. These results demonstrate that PTK787/ZK 222584 is a potent inhibitor of tumor growth, metastases formation, and tumor vascularization in murine renal cell carcinoma. Furthermore, we have been able to demonstrate that color Doppler imaging ultrasound can be used to measure blood flow to a tumor and that flow correlates with vessel density. Thus, this may be a valuable noninvasive method for monitoring the effects of antiangiogenic agents such as PTK787/ZK 222584 on tumor vasculature.

The role of enhanced Doppler ultrasound in differentiation of benign vs. malignant scar lesion after breast surgery for malignancy.

AIM: To evaluate the benefit of echo-contrast-enhanced Doppler sonography in the differentiation of benign vs. malignant breast lesions after surgical removal of a malignant breast mass. METHODS: Thirty-eight patients referred for biopsy of a palpable, suspicious scar lesion 1-15 years (mean 3.3 years) after surgery for breast cancer were examined. During baseline ultrasound examination a subjective scoring system of the vascularity, the number, the regularity of vessels' course and their Doppler parameters were assessed. After injection of an ultrasound contrast agent (Levovist) the same scoring system was applied to the parameters together with enhancement kinetics, enhancement intensity and enhancement pattern. Any increase in the scoring level of two or more characteristics (vascularity, number of vessels, intensity of enhancement in the tumor or regularity score of vessels in the lesion) was defined as suspicious for malignancy. A marked increase of enhancement in the immediate tumor periphery was also regarded as suspicious for malignancy. The sonographic results were assessed prospectively and correlated with the histology of the lesion. RESULTS: Of the 38 patients with a clinically-suspicious scar lesion, there were 28 true scars and 10 malignant scar lesions. All scar lesions showed no or slight vascularity on baseline sonography. After Echocontrast-enhancement a significant increase in tumor vascularity and the number of tumor vessels could be demonstrated in all 10 malignant lesions but in only one of the 28 benign scars. CONCLUSION: Scars pose inherent technical problems for optimal mammography. Sonographic evaluation of the vascularity of the lesion with contrast enhancing agents showed improved diagnostic accuracy in the hands of an experienced examiner.

Ultrasound demonstration of mammographically detected microcalcifications.

PURPOSE: To evaluate the capabilities of breast ultrasound (US) for identifying microcalcifications in benign breast changes, in situ carcinomas, and small nonpalpable invasive carcinomas. MATERIAL AND METHODS: Forty-six consecutive patients with 49 clustered microcalcifications detected by mammography were included in this prospective study. Patients with palpable breast lesions were excluded. Breast US was performed with knowledge of mammographic findings for presence and visibility of microcalcifications, and for parenchymal structure abnormalities. Mammographic and US findings were compared with histology. RESULTS: Nine ductal in situ carcinomas, 2 lobular in situ carcinomas, 11 invasive carcinomas and 27 benign lesions were confirmed by histology. For all lesions, US achieved a sensitivity of 75% in the detection of microcalcifications. The detection rate for microcalcification in invasive and in situ carcinomas was 100%. In 11 cases, no microcalcifications were visible on US; they all proved to be benign on histology. CONCLUSION: Microcalcifications in malignant lesions are reliably recognized by US. They are, however, difficult to detect in fibrocystic breast changes.