Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) - Part 1 with Recommendations for the Screening, Diagnosis and Therapy of Breast Cancer.

Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Methods The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure. Recommendations Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.

Comparison of Two Different Ultrasound Devices Using Strain Elastography Technology in the Diagnosis of Breast Lesions Related to the Histologic Results.

This study was conducted to provide evidence that elastograms of two different devices and different manufacturers using the same technical approach provide the same diagnoses. A total of 110 breast lesions were prospectively analysed by two experts in ultrasound, using the strain elastography function from two different manufacturers (Hitachi HI-RTE, Hitachi Medical Systems, Wiesbaden, Germany; and Siemens eSie Touch, Siemens Medical Systems, Erlangen, Germany). Results were compared with the histopathologic results. Applying the Bowker test of symmetry, no statistically significant difference between the two elastography functions of these two devices was found (p = 0.120). The Cohen's kappa of k = 0.591 showed moderate strength of agreement between the two elastograms. The two examiners yielded moderate strength of agreement analysing the elastograms (Hitachi HI-RTE, k = 0.478; Siemens eSie Touch, k = 0.441). In conclusion, evidence is provided that elastograms of the same lesion generated by two different ultrasound devices equipped with a strain elastography function do not significantly differ.

Ultrasonographic examination of the endometrium and myometrium using acoustic radiation force impulse (ARFI) imaging technology: An initial experience with a new method.

PURPOSE: Acoustic radiation force impulse (ARFI) imaging technology provides measurable values of the elasticity/stiffness of the tissues examined. This work is a pilot study to determine the shear wave velocity values of normal endometrium and myometrium in healthy asymptomatic women. METHODS: In a prospective observational study that recruited asymptomatic women, we used the ARFI (Virtual Touch tissue quantification(™); Siemens Medical Solutions) to examine six different points in the uterus of each woman; two points in the endometrium and four points in the myometrium. Two readings were obtained at each of the examined points to test the intra-observer reproducibility. RESULTS: A total of 32 women were recruited. The age range was 19-68 years with a median age of 42 years. The menopausal status did not have any significant influence on the shear wave velocity measurements. The mean readings in the endometrium were 1.96, 2.03, 2.04 and 2.08 m/s while in the myometrium they were 2.78, 2.85, 2.87, 2.89, 2.91, 2.99, 3.2 and 3.23 m/s, respectively. CONCLUSIONS: The ARFI procedure is a novel, reproducible ultrasonographic modality that can provide information about tissue stiffness. Transvaginal transducers fitted with this technology are sought as well as larger studies validating our findings.

Diagnostic performance and inter-observer concordance in lesion detection with the automated breast volume scanner (ABVS).

BACKGROUND: Automated whole breast ultrasound scanners of the latest generation have reached a level of comfortable application and high quality volume acquisition. Nevertheless, there is a lack of data concerning this technology. We investigated the diagnostic performance and inter-observer concordance of the Automated Breast Volume Scanner (ABVS) ACUSON S2000™ and questioned its implications in breast cancer diagnostics. METHODS: We collected 100 volume data sets and created a database containing 52 scans with no detectable lesions in conventional ultrasound (BI-RADS®-US 1), 30 scans with benign lesions (BI-RADS®-US 2) and 18 scans with breast cancer (BI-RADS®-US 5).Two independent examiners evaluated the ABVS data on a separate workstation without any prior knowledge of the patients' histories. RESULTS: The inter-rater reliability reached fair agreement (κ=0.36; 95% confidence interval (CI): 0.19-0.53). With respect to the true category, the conditional inter-rater validity coefficient was κ=0.18 (95% CI: 0.00-0.26) for the benign cases and κ=0.80 (95% CI: 0.61-1.00) for the malignant cases.Combining the assessments of examiner 1 and examiner 2, the diagnostic accuracy (AC), sensitivity (SE) and specificity (SP) for the experimental ABVS were AC = 79.0% (95% CI: 67.3-86.1), SE = 83.3% (95% CI: 57.7-95.6) and SP = 78.1% (% CI: 67.3-86.1), respectively.However, after the ABVS examination, there were a high number of requests for second-look ultrasounds in up to 48.8% of the healthy women due to assumed suspicious findings in the volume data.In an exploratory analysis, we estimated that an ABVS examination in addition to mammography alone could detect a relevant number of previously occult breast cancers (about 1 cancer in 300 screened and otherwise healthy women). CONCLUSIONS: The ABVS is a reliable imaging method for the evaluation of the breast with high sensitivity and a fair inter-observer concordance. However, we have to overcome the problem of the high number of false-positive results. Therefore, further prospective studies in larger collectives are necessary to define standard procedures in image acquisition and interpretation. Nevertheless, we consider the ABVS as being suitable for integration into breast diagnostics as a beneficial and reliable imaging method.

Acoustic radiation force impulse imaging with Virtual Touch™ tissue quantification: mean shear wave velocity of malignant and benign breast masses.

Acoustic radiation force impulse imaging (ARFI) with Virtual Touch™ tissue quantification (VTTQ) enables the determination of shear wave velocity (SWV) in meters per second (m/s). The aim of our study was to describe the mean SWV in normal breast tissue and various breast masses. We performed measurements of SWV with ARFI VTTQ in 145 breast masses (57 malignant, 88 benign) and in the adjacent breast parenchyma and adipose tissue. The mean SWV as well as the rate of successful measurements were analyzed. The difference between adipose tissue and parenchyma was statistically significant (3.05 versus 3.65 m/s) (P < 0.001). Focusing on breast masses, numerous measurements exceeded the upper limit of possible measurement (≥9.10 m/s, indicated as "X.XX m/s"). Nevertheless, the difference between the malignant and benign masses was statistically significant (8.38 ± 1.99 m/s versus 5.39 ± 2.95 m/s) (P < 0.001). The best diagnostic accuracy (75.9%) was achieved when the cutoff point for malignancy was set to 9.10 m/s in ARFI VTTQ. This implies that the SWV was regarded as suspicious when the upper limit of possible measurement was exceeded and the machine returned the value X.XX m/s. In conclusion, ARFI VTTQ is a feasible method for measurement of SWV in a region of interest. Furthermore, we propose the event of a highly elevated SWV as a significant criterion for malignancy. However, the method is technically not yet fully developed, and the problem of unsuccessful measurements must still be solved.

Acoustic radiation force impulse imaging with virtual touch tissue quantification: measurements of normal breast tissue and dependence on the degree of pre-compression.

Acoustic radiation force impulse imaging (ARFI) with Virtual Touch tissue quantification (VTTQ) enables the determination of shear wave velocity in meters per second (m/s). We investigated shear wave velocity in normal breast tissue and analyzed the influence of the degree of pre-compression on the measurements. In repeated measurements and with normal pre-compression, the mean shear wave velocity in breast parenchyma was significantly higher than that in breast adipose tissue (3.33 ± 1.18 m/s vs. 2.90 ± 1.10 m/s; p < 0.001; 712 measurements in 89 patients). Furthermore, we found a significant positive correlation between degree of pre-compression and velocity measurements. Shear wave velocities with low, moderate and high pre-compression were 1.89, 3.18 and 4.39 m/s in parenchyma, compared with 1.46, 2.55 and 3.64 m/s in adipose tissue, respectively (p < 0.001; 360 measurements in 60 patients). VTTQ of breast tissue is a feasible method with high accuracy; however, the degree of pre-compression applied may significantly influence the measurements.

Evaluation of real-time tissue sono-elastography in the assessment of 214 breast lesions: limitations of this method resulting from different histologic subtypes, tumor size and tumor localization.

Real-time sono-elastography is an ultrasound-based technique used to estimate tissue elasticity. Several publications have reported that this method has the ability to differentiate between malignant and benign breast lesions. However, on the basis of current literature, sono-elastography returned false-negative results in 25% of cases with certain lesions, such as mucinous carcinoma. Our data indicate that elastography has higher specificity (96.5% vs. 84.4%) and lower sensitivity (86.9% vs. 93.9%) than B-mode ultrasound. Our evidence suggests that elastography performs significantly worse in lesions ≥20 mm in diameter (sensitivity = 61.1%, specificity = 97.2%) than in lesions <20 mm in diameter (sensitivity = 92.6%, specificity = 96.2%). Furthermore, elastography returned false-negative results in all cases mucinous carcinoma. Finally, in eight cases we obtained a valid elastogram. Our data indicate that this finding is probably due to tumor depth.

Ultrasound real-time elastography can predict malignancy in BI-RADS®-US 3 lesions.

BACKGROUND: Lesions of the breast that are classified BI-RADS®-US 3 by ultrasound are probably benign and observation is recommended, although malignancy may occasionally occur. In our study, we focus exclusively on BI-RADS®-US 3 lesions and hypothesize that sonoelastography as an adjunct to conventional ultrasound can identify a high-risk-group and a low-risk-group within these patients. METHODS: A group of 177 breast lesions that were classified BI-RADS®-US 3 were additionally examined with real-time sonoelastography. Elastograms were evaluated according to the Tsukuba Elasticity Score. Pretest and posttest probability of disease (POD), sensitivity (SE), specificity (SP), positive (PPV) and negative predictive values (NPV) and likelihood-ratios (LR) were calculated. Furthermore, we analyzed the false-negative and false-positive cases and performed a model calculation to determine how elastography could affect the proceedings in population screening. RESULTS: In our collection of BI-RADS®-US 3 cases there were 169 benign and eight malignant lesions. The pretest POD was 4.5% (95% confidence interval (CI): 2.1-9.0). In patients with a suspicious elastogram (high-risk group), the posttest POD was significantly higher (13.2%, p = 0.041) and the positive LR was 3.2 (95% CI: 1.7-5.9). With a benign elastogram (low-risk group), the posttest POD decreased to 2.2%. SE, SP, PPV and NPV for sonoelastography in BI-RADS®-US 3 lesions were 62.5% (95% CI: 25.9-89.8), 80.5% (95% CI: 73.5-86.0), 13.2% (95% CI: 5.0-28.9) and 97.8% (95% CI: 93.3-99.4), respectively. CONCLUSIONS: Sonoelastography yields additional diagnostic information in the evaluation of BI-RADS®-US 3 lesions of the breast. The examiner can identify a low-risk group that can be vigilantly observed and a high-risk group that should receive immediate biopsy due to an elevated breast cancer risk.

Sonographic features of triple-negative and non-triple-negative breast cancer.

OBJECTIVES: Triple-negative breast cancer (TNBC) is known to have unique molecular, clinical, and pathologic characteristics. The growth pattern of this cancer may also affect its appearance on sonography. Our study evaluated the sonographic features of TNBC according to the American College of Radiology Breast Imaging Reporting and Data System sonographic classification system and compared these features with those of non-TNBC. METHODS: Data from 315 consecutive breast cancer cases were collected. The images were reevaluated by an examiner blinded to the patients' characteristics and histologic results according to the Breast Imaging Reporting and Data System. The sonographic features of TNBC (n = 33) and non-TNBC (n = 282) were compared. RESULTS: Triple-negative breast cancer was significantly correlated with a younger patient age (P = .002) and was associated with higher tumor grades (P < .001), more lymph node involvement (P = .014), and a trend toward a larger tumor size. With regard to sonographic features, the margin of TNBC was more frequently described as lobulated or microlobulated (75.8% versus 49.5% in non-TNBC; P = .005). The echoic halo was observed significantly less often in TNBC than in non-TNBC(39.4% versus 62.8%; P = .014). Cooper ligaments were displaced rather than disrupted in TNBC compared to non-TNBC (P = .003). Regarding the posterior acoustic features, enhancement was observed significantly more often in TNBC (36.4% versus 13.0% in non-TNBC; P = .031). CONCLUSIONS: Triple-negative breast cancer and non-TNBC have different sonographic features. This finding can be explained by the pathologic profile of this breast cancer subtype. Some of the distinct sonographic criteria for TNBC are more likely to be associated with benign masses. Knowledge of the distinct sonographic features of TNBC would help the examiner avoid false-negative classification of this tumor type.

Axillary dissection in primary breast cancer: variations of the surgical technique and influence on morbidity.

Lymphedema of the arm is the most common and impairing complication after breast cancer surgery with axillary lymph node dissection (ALND). Our prospective study evaluated the effect of two different surgical techniques for ALND on postoperative morbidity. Patients were scheduled to undergo ALND. Patients in group 1 (n = 17) underwent the most common and standard technique of ALND, which uses sharp dissection of the tissue and subsequent electro-coagulation of bleedings. Patients in group 2 (n = 17) underwent a modified standard technique of ALND with clamping and ligatures of all resection margins. Postoperative wound secretion was quantified and patients were followed up for 6 months to assess long-term morbidity. The variations in surgical technique had no significant influence on the outcome variables. However, patients in group 2 showed a tendency to less wound secretion (713 versus 802 mL; P = nonsignificant), a decreased rate of immediate postoperative seromas (11.8 versus 23.5%; P = nonsignificant) and less lymphedema after 3 months (29.4 versus 41.2%; P = nonsignificant). Moreover, the number of resected lymph nodes correlated with the total amount of drained fluid (P = 0.006), the duration of the drain (P = 0.015), and the risk for the development of lymphedema after 3 months (P = 0.016). The described variations in surgical technique had no influence on the outcomes of the patients. The number of resected axillary lymph nodes remains the most important risk factor for treatment-related morbidity. Therefore, a well-balanced choice of the extent of the axillary dissection should be the surgeon's main concern.

Variations in the Elasticity of Breast Tissue During the Menstrual Cycle Determined by Real-time Sonoelastography.

OBJECTIVES: The purpose of this study was to determine the dependence of breast tissue elasticity on the menstrual cycle of healthy volunteers by means of real-time sonoelastography. METHODS: Twenty-two healthy volunteers (aged 18-33 years) were examined once weekly during two consecutive menstrual cycles using sonoelastography. Group 1 (n= 10) was not taking hormonal medication; group 2 (n = 12) was taking oral contraceptives. RESULTS: The breast parenchyma appeared softer than the dermis and harder than the adipose tissue, and elasticity varied over the menstrual cycle and between groups. Group 1 (no hormone intake) showed continuously increasing elasticity with relatively soft breast parenchyma in the menstrual and follicular phases and harder parenchyma in the luteal phase (P = .012). Group 2 (oral contraceptives) showed no statistically significant changes in breast parenchymal elasticity according to sonoelastography. The parenchyma was generally softer in group 1 compared with group 2 throughout the menstrual cycle (P = .033). The dermis, the subcutaneous adipose tissue, and the pectoralis major muscle showed no changes in elasticity. Comparison of measurements made during the first and the second menstrual cycles showed similar patterns of elasticity in both groups. CONCLUSIONS: Sonoelastography is a reproducible method that can be used to determine the dependence of breast parenchyma elasticity on the menstrual cycle and on the intake of hormonal contraceptives.

The Automated Breast Volume Scanner (ABVS): initial experiences in lesion detection compared with conventional handheld B-mode ultrasound: a pilot study of 50 cases.

The idea of an automated whole breast ultrasound was developed three decades ago. We present our initial experiences with the latest technical advance in this technique, the automated breast volume scanner (ABVS) ACUSON S2000(™). Volume data sets were collected from 50 patients and a database containing 23 women with no detectable lesions in conventional ultrasound (BI-RADS(®)-US 1), 13 women with clearly benign lesions (BI-RADS(®)-US 2), and 14 women with known breast cancer (BI-RADS(®)-US 5) was created. An independent examiner evaluated the ABVS data on a separate workstation without any prior knowledge of the patients' histories. The diagnostic accuracy for the experimental ABVS was 66.0% (95% confidence interval [CI]: 52.9-79.1). The independent examiner detected all breast cancers in the volume data resulting in a calculated sensitivity of 100% in the described setting (95% CI: 73.2%-100%). After the ABVS examination, there were a high number of requests for second-look ultrasounds in 47% (95% CI: 30.9-63.5) of the healthy women (with either a clearly benign lesion or no breast lesions at all in conventional handheld ultrasound). Therefore, the specificity remained at 52.8% (95% CI: 35.7-69.2). When comparing the concordance of the ABVS with the gold standard (conventional handheld ultrasound), Cohen's Kappa value as an estimation of the inter-rater reliability was κ = 0.37, indicating fair agreement. In conclusion, the ABVS must still be regarded as an experimental technique for breast ultrasound, which definitely needs to undergo further evaluation studies.

Optimizing breast cancer follow-up: diagnostic value and costs of additional routine breast ultrasound.

A total of 2,546,325 breast cancer survivors are estimated to live in the United States. The organized breast cancer follow-up programs do not generally include breast ultrasound in asymptomatic women. The purpose of our prospective study was to investigate the efficacy of breast ultrasound in detecting previously occult recurrences. A total of 735 eligible patients with a history of breast cancer were recruited. We assessed the same patient population before (routine follow-up program) and after (study follow-up program) the introduction of an additional ultrasound examination. In the routine follow-up program 245 of 735 patients (33.3% [95% confidence-interval (CI): 29.9-36.7]) had an ultrasound due to abnormal local or mammographic findings. 490 of 735 patients (66.7% [95% CI: 63.3-70.1]) were initially considered asymptomatic and received an additional ultrasound exclusively within the study follow-up program. All positive examination results were followed by accelerated core needle biopsy. The routine follow-up program led to a biopsy in 66 of 735 patients (9.0%) revealing a recurrent cancer in 27 cases (3.7%). The study follow-up program with the additional ultrasound led to another 21 biopsies raising the total number of patients who had to undergo a biopsy from 9.0% (95% CI: 6.9-11.1) to 11.8% (95% CI: 9.5-14.2). Finally, we diagnosed a previously occult malignant lesion in an additional six patients following this protocol. Therefore, the rate of detected recurrences rose from 3.7% (95% CI: 2.3-5.0) in the routine follow-up program to 4.5% (95% CI: 3.0-6.0) in the study follow-up program (p = 0.041). Negative side effects were the additional costs (the costs per detected malignancy in the routine follow-up program were $2455.69; the costs for each additionally detected malignancy in the study follow-up program were $7580.30), the higher overall biopsy rate (9.0 vs. 11.8%) and the elevated benign biopsies rate (59.1% vs. 71.4%). Regarding these results, the advantages and disadvantages of additional breast ultrasound must be discussed for every follow-up patient individually even today, as we can detect a significantly higher number of previously occult malignancies.

Significant differentiation of focal breast lesions: calculation of strain ratio in breast sonoelastography.

RATIONALE AND OBJECTIVES: Initial data suggest that elastography can improve the specificity of ultrasound in differentiating benign and malignant breast lesions. The aim of this study was to compare elastography and B-mode ultrasound to determine whether the calculation of strain ratios (SRs) can further improve the differentiation of focal breast lesions. MATERIALS AND METHODS: A total of 227 women with histologically proven focal breast lesions (113 benign, 114 malignant) were included at two German breast centers. The women underwent a standardized ultrasound procedure using a high-end ultrasound system with a 9-MHz broadband linear transducer. B-mode scans and sonoelastograms were analyzed by two experienced readers using the Breast Imaging Reporting and Data System criteria. SRs were calculated from a tumor-adjusted region of interest (mean color pixel density) and a comparable region of interest placed in the lateral fatty tissue. Sensitivity, specificity, and cutoff values were calculated for SRs (receiver-operating characteristic analysis). RESULTS: The women had a mean age of 54 years (range, 19-87 years). The mean lesion diameter was 1.6 +/- 0.9 cm. Sensitivity and specificity were 96% and 56% for B-mode scanning, 81% and 89% for elastography, and 90% and 89% for SRs. An SR cutoff value of 2.45 (area under the curve, 0.949) allowed significant differentiation (P < .001) of malignant (mean, 5.1 +/- 4.2) and benign (mean, 1.6 +/- 1.0) lesions. The quantitative method of SR calculation was superior to subjective interpretation of sonoelastograms and B-mode scans, with a positive predictive value of 89% compared to 68% and 84% for the other two methods. CONCLUSIONS: Calculation of SRs contributes to the standardization of sonoelastography with high sensitivity and allows significant differentiation of benign and malignant breast lesions with higher specificity compared to B-mode ultrasound but not elastography.

Early detection of breast cancer: benefits and risks of supplemental breast ultrasound in asymptomatic women with mammographically dense breast tissue. A systematic review.

BACKGROUND: Mammographic screening alone will miss a certain fraction of malignancies, as evidenced by retrospective reviews of mammograms following a subsequent screening. Mammographic breast density is a marker for increased breast cancer risk and is associated with a higher risk of interval breast cancer, i.e. cancer detected between screening tests. The purpose of this review is to estimate risks and benefits of supplemental breast ultrasound in women with negative mammographic screening with dense breast tissue. METHODS: A systematic search and review of studies involving mammography and breast ultrasound for screening of breast cancer was conducted. The search was performed for the period 1/2000-8/2008 within the data source of PubMed, DARE, and Cochrane databases. Inclusion and exclusion criteria were determined prospectively, and the Oxford evidence classification system for diagnostic studies was used for evidence level. The parameters biopsy rate, positive predictive value (PPV) for biopsy, cancer yield for breast ultrasound alone, and carcinoma detection rate by breast density were extracted or constructed. RESULTS: The systematic search identified no randomized controlled trials or systematic reviews, six cohort studies of intermediate level of evidence (3b) were found. Only two of the studies included adequate follow-up of subjects with negative or benign findings. Supplemental breast ultrasound after negative mammographic screening permitted diagnosis of primarily invasive carcinomas in 0.32% of women in breast density type categories 2-4 of the American College of Radiology (ACR); mean tumor size for those identified was 9.9 mm, 90% with negative lymph node status. Most detected cancers occurred in mammographically dense breast ACR types 3 and 4. Biopsy rates were in the range 2.3%-4.7%, with PPV of 8.4-13.7% for those biopsied due to positive ultrasound, or about one third of the PPV of biopsies due to mammography. LIMITATIONS: The study populations included wide age ranges, and the application to women age 50-69 years as proposed for mammographic screening could result in less striking benefit. Further validation studies should employ a uniform assessment system such as BI-RADS and report not only PPV, but also negative predictive value, sensitivity and specificity. CONCLUSION: Supplemental breast ultrasound in the population of women with mammographically dense breast tissue (ACR 3 and 4) permits detection of small, otherwise occult, breast cancers. Potential adverse impacts for women in this intermediate risk group are associated with an increased biopsy rate.