Minimally Invasive Breast Biopsy After Neoadjuvant Systemic Treatment to Identify Breast Cancer Patients with Residual Disease for Extended Neoadjuvant Treatment: A New Concept.

BACKGROUND: Breast cancer patients with residual disease after neoadjuvant systemic treatment (NAST) have a worse prognosis compared with those achieving a pathologic complete response (pCR). Earlier identification of these patients might allow timely, extended neoadjuvant treatment strategies. We explored the feasibility of a vacuum-assisted biopsy (VAB) after NAST to identify patients with residual disease (ypT+ or ypN+) prior to surgery. METHODS: We used data from a multicenter trial, collected at 21 study sites (NCT02948764). The trial included women with cT1-3, cN0/+ breast cancer undergoing routine post-neoadjuvant imaging (ultrasound, MRI, mammography) and VAB prior to surgery. We compared the findings of VAB and routine imaging with the histopathologic evaluation of the surgical specimen. RESULTS: Of 398 patients, 34 patients with missing ypN status and 127 patients with luminal tumors were excluded. Among the remaining 237 patients, tumor cells in the VAB indicated a surgical non-pCR in all patients (73/73, positive predictive value [PPV] 100%), whereas PPV of routine imaging after NAST was 56.0% (75/134). Sensitivity of the VAB was 72.3% (73/101), and 74.3% for sensitivity of imaging (75/101). CONCLUSION: Residual cancer found in a VAB specimen after NAST always corresponds to non-pCR. Residual cancer assumed on routine imaging after NAST corresponds to actual residual cancer in about half of patients. Response assessment by VAB is not safe for the exclusion of residual cancer. Response assessment by biopsies after NAST may allow studying the new concept of extended neoadjuvant treatment for patients with residual disease in future trials.

Improved emptying performance with a new micro-hole zone catheter in adult male intermittent catheter users: A comparative multi-center randomized controlled cross-over study.

AIMS: To confirm the improved performance of the micro-hole zone catheter (MHZC) compared to a conventional eyelet catheter (CEC) in male users of clean intermittent catheterizations (CICs). METHODS: Male self-catheterizing subjects, who used hydrophilic sleeved soft/flexible CIC as the only bladder emptying method, were enrolled into a multi-center, randomized, cross-over study performed across six European sites. Subjects tested the MHZC, featuring a drainage zone with 120 micro-holes and a CEC with two eyelets. The study consisted of four study visits (V0-V3), during which endpoints related to catheter performance (urinary flow-stops, bladder emptying, and intra-catheter pressure) were measured and two 4-week test periods at home (T1 and T2) where dipstick hematuria and user perception between catheters were evaluated. RESULTS: Seventy-three male subjects with non-neurogenic and neurogenic bladder dysfunction (3:2) were enrolled. On average, catheterizations with the MHZC led to close to mean zero flow-stops compared to ≥1 flow-stops with the CEC, during both HCP- and self-led catheterizations (both p < 0.001). Residual urine at first flow-stop was significantly reduced for the MHZC compared to CEC (p = 0.001 and p = 0.004, for HCP- and self-led catheterizations, respectively). This was substantiated by a significantly smaller pressure peak at first flow-stop, a proxy for minimized mucosal suction (both HCP- and self-led catheterizations, p < 0.001). After home-use catheterizations, dipstick hematuria was comparable between catheters, whereas catheterizations were associated with significantly improved perception in favor of MHZC regarding bladder emptying, less blocking sensation, and improved hygienic catheterization compared to the CEC. CONCLUSION: This study confirmed the evidence of improved bladder emptying with the MHZC compared to a CEC without the need to reposition the catheter. The MHZC therefore offers an enhanced benefit for the dependent CIC user securing complete bladder emptying in an uninterrupted free flow and reducing the need to reposition the catheter during emptying.

Ultrasound-guided breast-conserving surgery compared to conventional breast-conserving surgery.

PURPOSE: The goal of breast-conserving surgery is to achieve negative tumor margins, since insufficient marginal distance is associated with more local and distant recurrences. This study investigates whether IOUS (intraoperative ultrasound) can reduce the re-resection rate compared to standard breast surgery, regardless of tumor biology and focality. MATERIALS AND METHODS: The present study is a monocentric, prospective, randomized, and non-blinded parallel group study conducted between 7/2015 and 2/2018. Patients with sonographically visible breast cancer were randomized into two study arms: 1) breast-conserving surgery with IOUS; 2) conventional arm. RESULTS: 364 patients were included in the study and underwent surgery. Tumor biology, size, and focality were equally distributed in both groups (p = 0.497). The study arms did not differ significantly in the proportion of preoperative wire markings (p= 0.084), specimen weight (p = 0.225), surgery duration (p = 0.849), and the proportion of shavings taken intraoperatively (p = 0.903). Positive margins were present in 16.6% of the cases in the IOUS arm and in 20.8% in the conventional arm (p = 0.347). Re-operation was necessary after intraoperative shavings in 14.4% of cases in the US arm and in 21.3% in the conventional arm (p = 0.100). CONCLUSION: Although the present study showed a clear difference in the rate of positive tumor margins with IOUS compared to conventional breast surgery without IOUS, this was not statistically significant in contrast to the current literature. This could be due to the high expertise of the breast surgeons, the precise wire marking, or the fact that the IOUS technique was not standardized.

Soluble NKG2DLs Are Elevated in Breast Cancer Patients and Associate with Disease Outcome.

Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation of membrane-bound NKG2DLs in breast cancer has been demonstrated by immunohistochemistry. Tumor cells release NKG2DLs via proteolytic cleavage as soluble (s)NKG2DLs, which allows for effective immune escape and is associated with poor prognosis. In this study, we collected serum from 140 breast cancer (BC) and 20 ductal carcinoma in situ (DCIS) patients at the time of initial diagnosis and 20 healthy volunteers (HVs). Serum levels of sNKG2DLs were quantified through the use of ELISA and correlated with clinical data. The analyzed sNKG2DLs were low to absent in HVs and significantly higher in BC patients. For some of the ligands analyzed, higher sNKG2DLs serum levels were associated with the classification of malignant tumor (TNM) stage and grading. Low sMICA serum levels were associated with significantly longer progression-free (PFS) and overall survival (OS). In conclusion, we provide the first insights into sNKG2DLs in BC patients and suggest their potential role in tumor immune escape in breast cancer. Furthermore, our observations suggest that serum sMICA levels may serve as a prognostic parameter in the patients analyzed in this study.

Association between 21-gene-assay and detection of disseminated tumor cells in patients with early breast cancer: results from the IRMA trial.

PURPOSE: Disseminated tumor cells (DTCs) in the bone marrow (BM) are known to be of prognostic value for patients with early breast cancer (EBC). In addition to histopathological features, multigene expression assays, such as the commercially available 21-gene Breast Recurrence Score® assay, have been validated for evaluating prognosis and making decisions concerning adjuvant treatment in EBC. In a previous retrospective study from our group, the 21-gene assay was shown to be associated with DTC-detection. A secondary endpoint of the prospective IRMA trial was to evaluate the association between Recurrence Score® (RS) result and tumor cell dissemination in patients with EBC. METHODS: DTC-status and RS result were assessed in patients with ER-positive/HER2-negative EBC with 0-3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women's Health of Tuebingen University, Germany. RESULTS: Patients with a high RS result (≥ 26) were more frequently DTC-positive (22.6%) than patients with a low RS result (8.6%, p = 0.034). The odds for DTC-positivity increased with rising RS values (p = 0.047). CONCLUSION: We therefore confirm that a high genomic risk is associated with tumor cell dissemination into the BM. Further trials are needed to investigate whether therapeutic decisions could be further individualized by combining DTC-status and prognostic gene signature testing.

Potential of Lesion-to-Fat Elasticity Ratio Measured by Shear Wave Elastography to Reduce Benign Biopsies in BI-RADS 4 Breast Lesions.

OBJECTIVES: We evaluated whether lesion-to-fat ratio measured by shear wave elastography in patients with Breast Imaging Reporting and Data System (BI-RADS) 3 or 4 lesions has the potential to further refine the assessment of B-mode ultrasound alone in breast cancer diagnostics. METHODS: This was a secondary analysis of an international diagnostic multicenter trial (NCT02638935). Data from 1288 women with breast lesions categorized as BI-RADS 3 and 4a-c by conventional B-mode ultrasound were analyzed, whereby the focus was placed on differentiating lesions categorized as BI-RADS 3 and BI-RADS 4a. All women underwent shear wave elastography and histopathologic evaluation functioning as reference standard. Reduction of benign biopsies as well as the number of missed malignancies after reclassification using lesion-to-fat ratio measured by shear wave elastography were evaluated. RESULTS: Breast cancer was diagnosed in 368 (28.6%) of 1288 lesions. The assessment with conventional B-mode ultrasound resulted in 53.8% (495 of 1288) pathologically benign lesions categorized as BI-RADS 4 and therefore false positives as well as in 1.39% (6 of 431) undetected malignancies categorized as BI-RADS 3. Additional lesion-to-fat ratio in BI-RADS 4a lesions with a cutoff value of 1.85 resulted in 30.11% biopsies of benign lesions which correspond to a reduction of 44.04% of false positives. CONCLUSIONS: Adding lesion-to-fat ratio measured by shear wave elastography to conventional B-mode ultrasound in BI-RADS 4a breast lesions could help reduce the number of benign biopsies by 44.04%. At the same time, however, 1.98% of malignancies were missed, which would still be in line with American College of Radiology BI-RADS 3 definition of <2% of undetected malignancies.

The impact of rehabilitation sport on breast cancer-related lymphoedema and quality of life.

PURPOSE: Surgery and radiotherapy as part of breast cancer treatment can lead to lymphoedema of the upper extremities (breast cancer-related lymphoedema = BCRL) and reduce the quality of life (health-related quality of life = HRQoL). The aim of the present study was to investigate the influence of paddling in a dragon boat (PP) on HRQoL and BCRL in breast cancer survivors (BCS). METHODS: Between April and October 2017, a prospective case-control study evaluated the effects of PP compared to a control group. In the paddle group (n = 28), weekly arm circumference measurements were taken at four defined anatomic areas of the arm before and after training; in the control group (n = 70), the measurements were taken once a month. At the beginning and end of the study, questionnaires from both groups (SF 36, EORTC QLQ C30) were evaluated to understand the differences in HRQoL. RESULTS: The paddle group started with a higher HRQoL compared to the control group. Most interesting, whether the affected or unaffected arm, whether before or after training-the arm circumference decreased over time in the paddling group. A pre-existing lymphoedema was not negatively influenced by paddling. In the paddle group, the physical health was constant over the season, while the physical health of the control group decreased significantly over time. CONCLUSION: PP in a dragon boat does not lead to the development or worsening of pre-existing lymphoedema due to breast cancer therapy, and seems to have a positive effect on the quality of life.

The Potential of Shear Wave Elastography to Reduce Unnecessary Biopsies in Breast Cancer Diagnosis: An International, Diagnostic, Multicenter Trial.

PURPOSE: In this prospective, multicenter trial we evaluated whether additional shear wave elastography (SWE) for patients with BI-RADS 3 or 4 lesions on breast ultrasound could further refine the assessment with B-mode breast ultrasound for breast cancer diagnosis. MATERIALS AND METHODS: We analyzed prospective, multicenter, international data from 1288 women with breast lesions rated by conventional 2 D B-mode ultrasound as BI-RADS 3 to 4c and undergoing 2D-SWE. After reclassification with SWE the proportion of undetected malignancies should be < 2 %. All patients underwent histopathologic evaluation (reference standard). RESULTS: Histopathologic evaluation showed malignancy in 368 of 1288 lesions (28.6 %). The assessment with B-mode breast ultrasound resulted in 1.39 % (6 of 431) undetected malignancies (malignant lesions in BI-RADS 3) and 53.80 % (495 of 920) unnecessary biopsies (biopsies in benign lesions). Re-classifying BI-RADS 4a patients with a SWE cutoff of 2.55 m/s resulted in 1.98 % (11 of 556) undetected malignancies and a reduction of 24.24 % (375 vs. 495) of unnecessary biopsies. CONCLUSION: A SWE value below 2.55 m/s for BI-RADS 4a lesions could be used to downstage these lesions to follow-up, and therefore reduce the number of unnecessary biopsies by 24.24 %. However, this would come at the expense of some additionally missed cancers compared to B-mode breast ultrasound (rate of undetected malignancies 1.98 %, 11 of 556, versus 1.39 %, 6 of 431) which would, however, still be in line with the ACR BI-RADS 3 definition (< 2 % of undetected malignancies).

Best Practice Guideline - DEGUM Recommendations on Breast Ultrasound. / Best Practice Guideline ­ Empfehlungen der DEGUM zur Durchführung und Beurteilung der Mammasonografie.

Alongside mammography, breast ultrasound is an important and well-established method in assessment of breast lesions. With the "Best Practice Guideline", the DEGUM Breast Ultrasound (in German, "Mammasonografie") working group, intends to describe the additional and optional application modalities for the diagnostic confirmation of breast findings and to express DEGUM recommendations in this Part II, in addition to the current dignity criteria and assessment categories published in Part I, in order to facilitate the differential diagnosis of ambiguous lesions.The present "Best Practice Guideline" has set itself the goal of meeting the requirements for quality assurance and ensuring quality-controlled performance of breast ultrasound. The most important aspects of quality assurance are explained in this Part II of the Best Practice Guideline.

The Clinical Relevance of the NATALEE Study: Application of the NATALEE Criteria to a Real-World Cohort from Two Large German Breast Cancer Centers.

The NATALEE study showed a significant benefit in invasive disease-free survival (iDFS) for patients with HR+/HER2- early breast cancer (eBC) at intermediate and high risk of recurrence who were treated with the CDK4/6 inhibitor Ribociclib in combination with endocrine therapy (ET). This retrospective study aims to apply the NATALEE inclusion criteria to a representative real-world cohort to estimate the proportion of HR+/HER2- breast cancer patients eligible for adjuvant Ribociclib therapy. Patients who underwent full surgical treatment for eBC between January 2018 and December 2020 at two large German university breast cancer centers (University of Ulm, University of Tuebingen) were included. Descriptive statistics were used to characterize the patient population eligible for Ribociclib treatment based on the NATALEE study's inclusion criteria. Out of 2384 enrolled patients, 1738 had HR+/HER2- eBC, of whom 43% (747/1738) met the NATALEE inclusion criteria. Of note, these patients were older, received less chemotherapy and presented with less advanced tumor stages compared to the NATALEE study cohort. Additionally, compared to the NATALEE study cohort, fewer patients had lymph node involvement (72.4% vs. 88.7%). Our analysis suggests that approximately 43% of all HR+/HER2- breast cancer patients will qualify for Ribociclib treatment. Given the numerous treatment options for patients with HR+/HER2- eBC, as well as the differences between the NATALEE cohort and patients in the real-world clinical setting, future analyses will be needed to determine which patients would benefit most from adjuvant CDK4/6 inhibitor treatment.

Diagnosing Pathologic Complete Response in the Breast After Neoadjuvant Systemic Treatment of Breast Cancer Patients by Minimal Invasive Biopsy: Oral Presentation at the San Antonio Breast Cancer Symposium on Friday, December 13, 2019, Program Number GS5-03.

OBJECTIVE: We evaluated the ability of minimally invasive, image-guided vacuum-assisted biopsy (VAB) to reliably diagnose a pathologic complete response in the breast (pCR-B). SUMMARY BACKGROUND DATA: Neoadjuvant systemic treatment (NST) elicits a pathologic complete response in up to 80% of women with breast cancer. In such cases, breast surgery, the gold standard for confirming pCR-B, may be considered overtreatment. METHODS: This multicenter, prospective trial enrolled 452 women presenting with initial stage 1-3 breast cancer of all biological subtypes. Fifty-four women dropped out; 398 were included in the full analysis. All participants had an imaging-confirmed partial or complete response to NST and underwent study-specific image-guided VAB before guideline-adherent breast surgery. The primary endpoint was the false-negative rate (FNR) of VAB-confirmed pCR-B. RESULTS: Image-guided VAB alone did not detect surgically confirmed residual tumor in 37 of 208 women [FNR, 17.8%; 95% confidence interval (CI), 12.8-23.7%]. Of these 37 women, 12 (32.4%) had residual DCIS only, 20 (54.1%) had minimal residual tumor (<5 mm), and 19 of 25 (76.0%) exhibited invasive cancer cellularity of ≤10%. In 19 of the 37 cases (51.4%), the false-negative result was potentially avoidable. Exploratory analysis showed that performing VAB with the largest needle by volume (7-gauge) resulted in no false-negative results and that combining imaging and image-guided VAB into a single diagnostic test lowered the FNR to 6.2% (95% CI, 3.4%-10.5%). CONCLUSIONS: Image-guided VAB missed residual disease more often than expected. Refinements in procedure and patient selection seem possible and necessary before omitting breast surgery.

The importance of multi-modal imaging and clinical information for humans and AI-based algorithms to classify breast masses (INSPiRED 003): an international, multicenter analysis.

OBJECTIVES: AI-based algorithms for medical image analysis showed comparable performance to human image readers. However, in practice, diagnoses are made using multiple imaging modalities alongside other data sources. We determined the importance of this multi-modal information and compared the diagnostic performance of routine breast cancer diagnosis to breast ultrasound interpretations by humans or AI-based algorithms. METHODS: Patients were recruited as part of a multicenter trial (NCT02638935). The trial enrolled 1288 women undergoing routine breast cancer diagnosis (multi-modal imaging, demographic, and clinical information). Three physicians specialized in ultrasound diagnosis performed a second read of all ultrasound images. We used data from 11 of 12 study sites to develop two machine learning (ML) algorithms using unimodal information (ultrasound features generated by the ultrasound experts) to classify breast masses which were validated on the remaining study site. The same ML algorithms were subsequently developed and validated on multi-modal information (clinical and demographic information plus ultrasound features). We assessed performance using area under the curve (AUC). RESULTS: Of 1288 breast masses, 368 (28.6%) were histopathologically malignant. In the external validation set (n = 373), the performance of the two unimodal ultrasound ML algorithms (AUC 0.83 and 0.82) was commensurate with performance of the human ultrasound experts (AUC 0.82 to 0.84; p for all comparisons > 0.05). The multi-modal ultrasound ML algorithms performed significantly better (AUC 0.90 and 0.89) but were statistically inferior to routine breast cancer diagnosis (AUC 0.95, p for all comparisons ≤ 0.05). CONCLUSIONS: The performance of humans and AI-based algorithms improves with multi-modal information. KEY POINTS: • The performance of humans and AI-based algorithms improves with multi-modal information. • Multimodal AI-based algorithms do not necessarily outperform expert humans. • Unimodal AI-based algorithms do not represent optimal performance to classify breast masses.

Implementation of an Electronic Patient-Reported Outcome App for Health-Related Quality of Life in Breast Cancer Patients: Evaluation and Acceptability Analysis in a Two-Center Prospective Trial.

BACKGROUND: One in eight women is diagnosed with breast cancer in the course of their life. As systematic palliative treatment has only a limited effect on survival rates, the concept of health-related quality of life (HRQoL) was developed for measurement of patient-centered outcomes. Various studies have already demonstrated the reliability of paper-based patient-reported outcome (pPRO) and electronic patient-reported outcome (ePRO) surveys and that the 2 means of assessment are equally valid. OBJECTIVE: The aim of this study was to analyze the acceptance and evaluation of a tablet-based ePRO app for breast cancer patients and to examine its suitability, effort, and difficulty in the context of HRQoL and sociodemographic factors. METHODS: Overall, 106 women with adjuvant or advanced breast cancer were included in a 2-center study at 2 major university hospitals in Germany. Patients were asked to answer HRQoL and PRO questionnaires both on a tablet on-site using a specific eHealth assessment website and on paper. The suitability, effort, and difficulty of the app and self-reported technical skills were also assessed. Only the results of the electronically acquired data are presented here. The results of the reliability of the pPRO data have already been published elsewhere. RESULTS: Patients regarded the ePRO assessment as more suitable (80/106, 75.5%), less stressful (73/106, 68.9%), and less difficult (69/106, 65.1%) than pPRO. The majority of patients stated that ePRO assessment improves health care in hospitals (87/106, 82.1%). However, evaluation of ePROs depended on the level of education (P=.003) in the dimensions of effort and difficulty (regression analysis). The app was rated highly in all categories. HRQoL data and therapy setting did not show significant correlations with the app's evaluation parameters. CONCLUSIONS: The results indicate that ePRO surveys are feasible for measuring HRQoL in breast cancer patients and that those patients prefer ePRO assessment to pPRO assessment. It can also be seen that patients consider ePRO assessment to improve hospital health care. However, studies with larger numbers of patients are needed to develop apps that address the needs of patients with lower levels of education and technical skills.

Intraoperative Ultrasound-Guided Excision of Non-Palpable and Palpable Breast Cancer: Systematic Review and Meta-Analysis.

Wire-guided localization (WGL) is the most frequently used localization technique in non-palpable breast cancer (BC). However, low negative margin rates, patient discomfort, and the possibility of wire dislocation have been discussed as potential disadvantages, and re-operation due to positive margins may increase relapse risk. Intraoperative ultrasound (IOUS)-guided excision allows direct visualization of the lesion and the resection volume and reduces positive margins in palpable and non-palpable tumors. We performed a systematic review on IOUS in breast cancer and 2 meta-analyses of randomized clinical trials (RCTs). In non-palpable BC, 3 RCTs have shown higher negative margin rates in the IOUS arm compared to WGL. Meta-analysis confirmed a significant difference between IOUS and WGL in terms of positive margins favoring IOUS (risk ratio 4.34, p < 0.0001, I2 = 0%). 41 cohort studies including 3291 patients were identified, of which most reported higher negative margin and lower re-operation rates if IOUS was used. In palpable BC, IOUS was compared to palpation-guided excision in 3 RCTs. Meta-analysis showed significantly higher rates of positive margins in the palpation arm (risk ratio 2.84, p = 0.0047, I2 = 0%). In 13 cohort studies including 942 patients with palpable BC, negative margin rates were higher if IOUS was used, and tissue volumes were higher in palpation-guided cohorts in most studies. IOUS is a safe noninvasive technique for the localization of sonographically visible tumors that significantly improves margin rates in palpable and non-palpable BC. Surgeons should be encouraged to acquire ultrasound skills and participate in breast ultrasound training.

Best Practice Guideline - DEGUM Recommendations on Breast Ultrasound. / Best Practice Guideline ­ Empfehlungen der DEGUM zur Durchführung und Beurteilung der Mammasonografie ­ TEIL I ­ Untersuchungstechnik, Ultraschall-DEGUM-Kriterien und deren Dokumentation.

For many years, breast ultrasound has been used in addition to mammography as an important method for clarifying breast findings. However, differences in the interpretation of findings continue to be problematic 1 2. These differences decrease the diagnostic accuracy of ultrasound after detection of a finding and complicate interdisciplinary communication and the comparison of scientific studies 3. In 1999, the American College of Radiology (ACR) created a working group (International Expert Working Group) that developed a classification system for ultrasound examinations based on the established BI-RADS classification of mammographic findings under consideration of literature data 4. Due to differences in content, the German Society for Ultrasound in Medicine (DEGUM) published its own BI-RADS-analogue criteria catalog in 2006 3. In addition to the persistence of differences in content, there is also an issue with formal licensing with the current 5th edition of the ACR BI-RADS catalog, even though the content is recognized by the DEGUM as another system for describing and documenting findings. The goal of the Best Practice Guideline of the Breast Ultrasound Working Group of the DEGUM is to provide colleagues specialized in senology with a current catalog of ultrasound criteria and assessment categories as well as best practice recommendations for the various ultrasound modalities.

Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment.

Breast cancer represents the most common malignancy among women in the world. Although immuno-, chemo- and radiation therapy are widely recognized as the therapeutic trifecta, new strategies in the fight against breast cancer are continually explored. The local microenvironment around the tumor plays a great role in cancer progression and invasion, representing a promising therapeutic target. CCL5 is a potent chemokine with a physiological role of immune cell attraction and has gained particular attention in R&D for breast cancer treatment. Its receptor, CCR5, is a well-known co-factor for HIV entry through the cell membrane. Interestingly, biology research is unusually unified in describing CCL5 as a pro-oncogenic factor, especially in breast cancer. In silico, in vitro and in vivo studies blocking the CCL5/CCR5 axis show cancer cells become less invasive and less malignant, and the extracellular matrices produced are less oncogenic. At present, CCR5 blocking is a mainstay of HIV treatment, but despite its promising role in cancer treatment, CCR5 blocking in breast cancer remains unperformed. This review presents the role of the CCL5/CCR5 axis and its effector mechanisms, and names the most prominent hurdles for the clinical adoption of anti-CCR5 drugs in cancer.

Is casual employment in Australia bad for workers' health?

OBJECTIVES: This paper assessed the impact of working in casual employment, compared with permanent employment, on eight health attributes that make up the 36-Item Short Form (SF-36) Health Survey, separately by sex. The mental health impacts of casual jobs with irregular hours over which the worker reports limited control were also investigated. METHODS: Longitudinal data from the Household, Income and Labour Dynamics in Australia Survey, over the period 2001-2018, were used to investigate the relationship between the eight SF-36 subscales and workers' employment contract type. Individual, household and job characteristic confounders were included in dynamic panel data regression models with correlated random effects. RESULTS: For both men and women, health outcomes for casual workers were no worse than for permanent workers for any of the eight SF-36 health attributes. For some health attributes, scores for casual workers were higher (ie, better) than for permanent workers (role physical: men: ß=1.15, 95% CI 0.09 to 2.20, women: ß=1.79, 95% CI 0.79 to 2.80; bodily pain: women: ß=0.90, 95% CI 0.25 to 1.54; vitality: women: ß=0.65, 95% CI 0.13 to 1.18; social functioning: men: ß=1.00, 95% CI 0.28 to 1.73); role emotional: men: ß=1.81, 95% CI 0.73 to 2.89, women: ß=1.24, 95% CI 0.24 to 2.24). Among women (but not men), mental health and role emotional scores were lower for irregular casual workers than for regular permanent workers but not statistically significantly so. CONCLUSIONS: This study found no evidence that casual employment in Australia is detrimental to self-assessed worker health.

Evaluation of sonographic detectability of different markers within an in vitro simulation model of the axilla.

PURPOSE: Clip-marking of axillary lymph nodes with initial biopsy-confirmed metastasis is required for targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of the clipped targeted lymph node. There have been several studies which examined the feasibility of TAD in routine clinical use. In this context, the optimal clip visualisation was noted as one of the crucial limiting factors. We, therefore, evaluated the sonographic detectability of 10 different commercially available markers within an in vitro model simulating the anatomical composition of the axilla. METHODS: In this standardised model consisting of porcine fat with 30 mm thickness, the visibility of a total of ten markers was analysed in all 3 planes (parallel, diagonal, orthograde) with wire guidance and then classified into either "visibility good", "visibility moderate" or "visibility poor" with regard to the alignment of the transducer. Additionally, "real-life conditions" were simulated, in which the markers were searched without any wires guidance. RESULTS: It was observed that, while not all markers are detectable in fatty tissue, markers with spherical shape (non-embedded Inconel or Nitinol) or rectangular-shaped Titanium markers with embedded material have a clear advantage. 3D-shaped markers can always be detected in all three axes, which is of particular importance in the axilla with its pyramid shape and fatty tissue. CONCLUSION: The shape and the embedding of the material play a crucial role for visibility and efficacy of the marker, as reliable marking of suspicious and pathological axillary lymph nodes is essential for TAD.

Axillary ultrasound for prediction of response to neoadjuvant therapy in the context of surgical strategies to axillary dissection in primary breast cancer: a systematic review of the current literature.

PURPOSE: Data on the optimal treatment strategy for patients undergoing neoadjuvant therapy (NAT) who initially presented with metastatic nodes and convert to node-negative disease (cN+ → ycN0) are limited. Since NAT leads to axillary downstaging in 20-60% of patients, the question arises whether these patients might be offered less-invasive procedures than axillary dissection, such as sentinel node biopsy or targeted removal of lymph nodes marked before therapy. METHODS: We performed a systematic review of clinical studies on the use of axillary ultrasound for prediction of response to NAT and ultrasound-guided marking of metastatic nodes for targeted axillary dissection. RESULTS: The sensitivity of ultrasound for prediction of residual node metastasis was higher than that of clinical examination and MRI/PET in most studies; specificity ranged in large trials from 37 to 92%. The diagnostic performance of ultrasound after NAT seems to be associated with tumor subtype: the positive predictive value was highest in luminal, the negative in triple-negative tumors. Several trials evaluated the usefulness of ultrasound for targeted axillary dissection. Before NAT, nodes were most commonly marked using ultrasound-guided clip placement, followed by ultrasound-guided placement of a radioactive seed. After chemotherapy, the clip was detected on ultrasound in 72-83% of patients; a comparison of sonographic visibility of different clips is lacking. Detection rate after radioactive seed placement was ca. 97%. CONCLUSION: In conclusion, ultrasound improves prediction of axillary response to treatment in comparison to physical examination and serves as a reliable guiding tool for marking of target lymph nodes before the start of treatment. High quality and standardization of the examination is crucial for selection of patients for less-invasive surgery.

Percutaneous Ultrasound-Guided Core Needle Biopsy: Comparison of 16-Gauge versus 14-Gauge Needle and the Effect of Coaxial Guidance in 1065 Breast Biopsies - A Prospective Randomized Clinical Noninferiority Trial.

PURPOSE: Ultrasound-guided core needle biopsy (CNB) is considered the standard assessment to diagnose sonographically visible suspicious breast mass lesions. Based on nonrandomized trials, the current German guidelines recommend at least three cylinders with ≤ 14-gauge needle biopsy. However, no recommendation is made as to how many specimens are needed with a smaller needle size, such as 16-gauge, or if biopsy with coaxial guidance improves diagnostic accuracy and quality. Therefore, in a prospective monocentric unblinded randomized controlled clinical noninferiority trial, the diagnostic accuracy of 16-gauge versus 14-gauge core needle biopsy, with and without coaxial guidance, was evaluated. MATERIALS AND METHODS: 1065 breast biopsies were included in order to analyze the number of core samples necessary to obtain an appropriate rate of diagnostic quality adequate for histological evaluation, and to achieve high diagnostic accuracy and diagnostic yield. Histological results were verified by surgery or long-term follow-up of at least two years up to five years. RESULTS: In order to obtain an additive diagnostic accuracy of > 99 %, a minimum of two cylinders with 14-gauge biopsy were required. The diagnostic accuracy and the diagnostic quality of 14-gauge biopsy were not affected by the coaxial technique. When performing a 16-gauge biopsy, five cylinders were required to achieve an additive diagnostic accuracy of > 99 %. Without coaxial guidance, 16-gauge CNB required at least three samples, whereas five needle passes with coaxial-guided 16-gauge biopsy were needed. CONCLUSION: The diagnostic accuracy and quality of ultrasound-guided 16-gauge core needle biopsy were inferior to the 14-gauge needle size, regardless of the use of a coaxial technique.