[Ultrasound elastography techniques in breast cancer]. / Sonoelastographie der Mamma.

BACKGROUND: Elasticity assessment of breast lesions can also be used as an associated criterion in the B­mode ultrasound (US) assessment for differentiation between benign or malignant lesions. OBJECTIVES: The goal was to identify techniques available to measure US elasticity, assess the use of B­mode BI-RADS® classification combined with elastography, and identify which artefacts influence the US elasticity result. MATERIALS AND METHODS: Based on different studies and meta-analyses, clinical application in daily routine of the presented US elastography techniques will be investigated concerning the statistical performance of semi-quantitative and quantitative cut-off values to differentiate benign from malignant lesions. RESULTS: Supported by meta-analyses, all presented US elastography techniques improve the specificity by decreasing the B­mode sensitivity. In the literature the semi-quantitative and quantitative cut-off values often vary considerably. The interobserver variability of strain elastography shows a fair agreement and the interobserver variability of shear wave elastography a substantial agreement. CONCLUSIONS: Considering the limitations and artefacts of each technique, US elastography is able to enhance the true positive and true negative results. In the case of a higher B­mode BI-RADS® classification (4b, 4c, 5) or in a high-risk situation to develop breast cancer, a large core needle biopsy should be performed despite lesion softness in elastography.

Radiologic complete response (rCR) in contrast-enhanced magnetic resonance imaging (CE-MRI) after neoadjuvant chemotherapy for early breast cancer predicts recurrence-free survival but not pathologic complete response (pCR).

BACKGROUND: Patients with early breast cancer (EBC) achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) have a favorable prognosis. Breast surgery might be avoided in patients in whom the presence of residual tumor can be ruled out with high confidence. Here, we investigated the diagnostic accuracy of contrast-enhanced MRI (CE-MRI) in predicting pCR and long-term outcome after NACT. METHODS: Patients with EBC, including patients with locally advanced disease, who had undergone CE-MRI after NACT, were retrospectively analyzed (n = 246). Three radiologists, blinded to clinicopathologic data, reevaluated all MRI scans regarding to the absence (radiologic complete remission; rCR) or presence (no-rCR) of residual contrast enhancement. Clinical and pathologic responses were compared categorically using Cohen's kappa statistic. The Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Overall rCR and pCR (no invasive tumor in the breast and axilla (ypT0/is N0)) rates were 45% (111/246) and 29% (71/246), respectively. Only 48% (53/111; 95% CI 38-57%) of rCR corresponded to a pCR (= positive predictive value - PPV). Conversely, in 87% (117/135; 95% CI 79-92%) of patients, residual tumor observed on MRI was pathologically confirmed (= negative predictive value - NPV). Sensitivity to detect a pCR was 75% (53/71; 95% CI 63-84%), while specificity to detect residual tumor and accuracy were 67% (117/175; 95% CI 59-74%) and 69% (170/246; 95% CI 63-75%), respectively. The PPV was significantly lower in hormone-receptor (HR)-positive compared to HR-negative tumors (17/52 = 33% vs. 36/59 = 61%; P = 0.004). The concordance between rCR and pCR was low (Cohen's kappa - 0.1), however in multivariate analysis both assessments were significantly associated with RFS (rCR P = 0.037; pCR P = 0.033) and OS (rCR P = 0.033; pCR P = 0.043). CONCLUSION: Preoperative CE-MRI did not accurately predict pCR after NACT for EBC, especially not in HR-positive tumors. However, rCR was strongly associated with favorable RFS and OS.

Can Cut-Off-Values for Tumor Size or Patient Age in Breast Ultrasound Reduce Unnecessary Biopsies or is it all About Bi-rads?- A Retrospective Analysis of 763 Biopsied T1-Sized Lesions.

AIMS AND OBJECTIVES: To assess whether it is possible to establish a size cut-off-value for sonographically visible breast lesions in a screening situation, under which it is justifiable to obviate a biopsy and to evaluate the grayscale characteristics of the identified lesions. MATERIALS AND METHODS: Images of sonographically visible and biopsied breast lesions of 684 patients were retrospectively reviewed and assessed for the following parameters: size, shape, margin, lesion boundary, vascularity, patient's age, side of breast, histological result, and initial BI-RADS category. Statistical analyses (t-test for independent variables, ROC analyses, binary logistic regression models, cross-tabulations, positive/negative predictive values) were performed using IBM SPSS (Version 21.0). RESULTS: Of all 763 biopsied lesions, 223 (29.2%) showed a malignant histologic result, while 540 (70.8%) were benign. Although we did find a statistically significant correlation of malignancy and lesion size (p=0.031), it was not possible to define a cut-off value, under which it would be justifiable to obviate a biopsy in terms of sensitivity and specificity (AUC: 0.558) at any age. Lesions showing the characteristics of a round or oval shape, a sharp delineation and no echogenic rim (n=112) were benign with an NPV of 99.1%. CONCLUSION: It is not possible to define a cut-off value for size or age, under which a biopsy of a sonographically visible breast lesion can be obviated in the screening situation. The combination of the 3 grayscale characteristics, shape (round or oval), margin (circumscribed) and no echogenic-rim sign, showed an NPV of 99.1%. Therefore, it seems appropriate to classify such lesions as BI-RADS 2.

Discovery of thiazolobenzoxepin PI3-kinase inhibitors that spare the PI3-kinase ß isoform.

A series of suitable five-membered heterocyclic alternatives to thiophenes within a thienobenzoxepin class of PI3-kinase (PI3K) inhibitors was discovered. Specific thiazolobenzoxepin 8-substitution was identified that increased selectivity over PI3Kß. PI3Kß-sparing compound 27 (PI3Kß Ki,app/PI3Kα Ki,app=57) demonstrated dose-dependent knockdown of pAKT, pPRAS40 and pS6RP in vivo as well as differential effects in an in vitro proliferation cell line screen compared to pan PI3K inhibitor GDC-0941. A new structure-based hypothesis for reducing inhibition of the PI3K ß isoform while maintaining activity against α, δ and γ isoforms is presented.

Breast Sonography - 2D, 3D, 4D Ultrasound or Elastography?

SUMMARY: The aim of this publication is to give an answer to the question whether 2D, 3D and 4D sonography of the breast can be replaced by elastography or whether elastography is an adjunct tool to B-mode imaging. The Breast Imaging and Reporting Data System (BI-RADS) ultrasound (US) descriptors of a lesion besides vascularity are based on B-mode imaging. US elastography displays the mechanical tissue properties. This information can be obtained by freehand compression and decompression. Acoustic radiation force impulse imaging (ARFI) produces stress with low-frequency push pulses. Manual compression by the transducer is not necessary. Shear wave elastography (SWE) is the combination of ARFI and the measurement of the consecutive shear wave propagations in the tissue. A quantification of the elasticity in kilopascal (kPa) is offered. Discussing B-mode imaging and elastography combined with the literature, elastography is seen as an addition to B-mode imaging with the potential to increase the specificity of the B-mode imaging-based BI-RADS assessment. In spite of additional elasticity information, the sensitivity remains high. A time-saving diagnostic algorithm for 2D, 3D US and elastography is described. In conclusion, it must be said that elasticity is not a stand-alone US modality able to replace 2D and 3D sonography.

Sentinel lymph node biopsy is precise after primary systemic therapy in stage II-III breast cancer patients.

BACKGROUND: Sentinel lymph node biopsy (SLNB) without axillary lymph node dissection (ALND) in SLN negative patients is a standard of care for most breast cancer patients. SLNB for axillary staging after primary systemic therapy (PST) is still under discussion because of possibly reduced accuracy, while data are lacking. The purpose of this study was to evaluate the accuracy of SLNB after PST. MATERIALS AND METHODS: A total of 185 breast cancer patients were treated with PST; 160 patients received preoperative chemotherapy, and 25 patients received preoperative endocrine therapy. Thus, 143 of 160 patients with preoperative chemotherapy and 22 of 25 patients with preoperative endocrine therapy were eligible for evaluation. The combination of blue dye and radioactive tracer was used for identification of SLNs. All patients received SLNB and axillary lymph node dissection (ALND). Pathologic assessment of SLNs was performed and compared to non-SLN status. RESULTS: Pathologic complete response rates and breast conserving therapy rates were 15.4 and 78.3% in the preoperative chemotherapy group and 0 and 77.3% in the preoperative endocrine therapy group, respectively. Identification rate, sensitivity, overall accuracy, and false-negative rate were 81.1% (116 of 143), 91.7% (55 of 60), 95.7% (111 of 116), and 8.3% (5 of 60) in the preoperative chemotherapy group and 77.3% (17 of 22), 90.0% (9 of 10), 94.1% (16 of 17), and 10.0% (1 of 10) in the preoperative endocrine therapy group, respectively. DISCUSSION: SLNB after primary systemic therapy is accurate, and the results are comparable to those of primary SLNB. SLNB after PST could spare ALND in up to 40% of patients with primary positive axillary lymph nodes and should be considered as a standard for axillary staging in those patients.

Structure-based optimization of pyrazolo-pyrimidine and -pyridine inhibitors of PI3-kinase.

Starting from HTS hit 1a, X-ray co-crystallization and molecular modeling were used to design potent and selective inhibitors of PI3-kinase. Bioavailablity in this series was improved through careful modulation of physicochemical properties. Compound 12 displayed in vivo knockdown of PI3K pharmacodynamic markers such as pAKT, pPRAS40, and pS6RP in a PC3 prostate cancer xenograft model.