Long-term outcomes of a randomized, open-label, phase II study comparing cabazitaxel versus paclitaxel as neoadjuvant treatment in patients with triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE).

BACKGROUND: The GENEVIEVE study, comparing neoadjuvant cabazitaxel versus paclitaxel in triple-negative breast cancer (TNBC) and luminal B/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC), previously reported significant differences in pathological complete response (pCR) rates. Effects on long-term outcome are unknown. PATIENTS AND METHODS: GENEVIEVE randomized patients with cT2-3, any cN or cT1, cN+/pNSLN+, centrally confirmed TNBC or luminal B/HER2-negative BC (latter defined as estrogen/progesterone receptor-positive and >14% Ki-67-stained cells) to receive either cabazitaxel 25 mg/m2 q3w for four cycles or paclitaxel 80 mg/m2 weekly for 12 weeks. Anthracycline-containing chemotherapy was allowed in case of histologically proven invasive residuals as neoadjuvant treatment or after surgery as adjuvant treatment. Here we report the secondary endpoints invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS). RESULTS: Of the 333 patients randomized, 74.7% and 83.2% completed treatment in the cabazitaxel and paclitaxel arms, respectively. After a median follow-up of 89.3 months (interquartile range 68.8-97.3 months), 80 iDFS events (43 after cabazitaxel and 37 after paclitaxel) and 47 deaths (23 after cabazitaxel and 24 after paclitaxel) were reported. IDFS rates were not significantly different between the cabazitaxel and paclitaxel arms after a 3-year (83.6% versus 85.0%) and 5-year follow-up (76.2% versus 78.3%) [hazard ratio (HR) = 1.27, 95% confidence interval 0.82-1.96, P = 0.294], respectively. DDFS rates at 3 years (88.6% versus 87.8%) and 5 years (82.1% versus 82.8%) for cabazitaxel and paclitaxel were comparable (HR = 1.15, P = 0.573). Similarly, OS rates at 3 years (91.6% versus 91.8%) and 5 years (89.2% versus 86.8%) showed no significant differences (HR = 1.05, P = 0.872). Subgroup analysis for TNBC and luminal B/HER2-negative BCs indicated no significant variations in 3- or 5-year iDFS, DDFS, or OS. CONCLUSIONS: The significant differences in pCR rates observed in both treatment arms did not significantly impact long-term outcomes for patients treated with cabazitaxel versus paclitaxel in the GENEVIEVE trial.

Carbohydrate-rich supplements can improve nitrogen use efficiency and mitigate nitrogenous gas emissions from the excreta of dairy cows grazing temperate grass.

Temperate pasture species constitute a source of protein for dairy cattle. On the other hand, from an environmental perspective, their high N content can increase N excretion and nitrogenous gas emissions by livestock. This work explores the effect of energy supplementation on N use efficiency (NUE) and nitrogenous gas emissions from the excreta of dairy cows grazing a pasture of oat and ryegrass. The study was divided into two experiments: an evaluation of NUE in grazing dairy cows, and an evaluation of N-NH3 and N-N2O volatilizations from dairy cow excreta. In the first experiment, 12 lactating Holstein × Jersey F1 cows were allocated to a double 3 × 3 Latin square (three experimental periods of 17 days each) and subjected to three treatments: cows without supplementation (WS), cows supplemented at 4.2 kg DM of corn silage (CS) per day, and cows supplemented at 3.6 kg DM of ground corn (GC) per day. In the second experiment, samples of excreta were collected from the cows distributed among the treatments. Aliquots of dung and urine of each treatment plus one blank (control - no excreta) were allotted to a randomized block design to evaluate N-NH3 and N-N2O volatilization. Measurements were performed until day 25 for N-NH3 and until day 94 for N-N2O. Dietary N content in the supplemented cows was reduced by 20% (P < 0.001) compared with WS cows, regardless of the supplement. Corn silage cows had lower N intake (P < 0.001) than WS and GC cows (366 v. 426 g/day, respectively). Ground corn supplementation allowed cows to partition more N towards milk protein compared with the average milk protein of WS cows or those supplemented with corn silage (117 v. 108 g/day, respectively; P < 0.01). Thus, even though they were in different forms, both supplements were able to increase (P < 0.01) NUE from 27% in WS cows to 32% in supplemented cows. Supplementation was also effective in reducing N excretion (761 v. 694 g/kg of Nintake; P < 0.001), N-NH3 emission (478 v. 374 g/kg of Nmilk; P < 0.01) and N-N2O emission (11 v. 8 g/kg of Nmilk; P < 0.001). Corn silage and ground corn can be strategically used as feed supplements to improve NUE, and they have the potential to mitigate N-NH3 and N-N2O emissions from the excreta of dairy cows grazing high-protein pastures.

Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients.

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

Evaluation of a Marker Clip System in Sonographically Guided Core Needle Biopsy for Breast Cancer Localization Before and After Neoadjuvant Chemotherapy.

Introduction The placement of intramammary marker clips has proven to be helpful for tumor localization in patients undergoing neoadjuvant chemotherapy and breast-conserving surgery. The purpose of our study was to investigate the feasibility of using a clip marker system for breast cancer localization and its influence on the imaging assessment of treatment responses after neoadjuvant chemotherapy. Patients and Methods Between March and June 2015, a total of 25 patients (n = 25), with a suspicion of invasive breast cancer with diameters of at least 2 cm (cT2), underwent preoperative sonographically guided core needle biopsy using a single-use breast biopsy system (HistoCore™) and intramammary clip marking using a directly adapted clip system based on the established O-Twist Marker™, before their scheduled preoperative neoadjuvant chemotherapy. Localization of the intramammary marker clip was controlled by sonography and digital breast tomosynthesis. Results Sonography detected no dislocation of intrammammary marker clips in 20 of 25 patients (80 %), while digital breast tomosynthesis showed accurate placement without dislocation in 24 patients (96 %) (p < 0.05). There was no evidence of significant clip migration during preoperative follow-up imaging after neoadjuvant chemotherapy. No complication related to the clip marking was noted and there was no difficulty in evaluating the treatment response to neoadjuvant chemotherapy. Among the breast-conserving surgeries performed, no cases were identified in which intraoperative loss of the marker clip had occurred. Conclusion Our study underscores the importance of intramammary marking clip systems before neoadjuvant chemotherapy. Placement of marker clips is advised to facilitate accurate tumor bed localization. With regard to digital breast tomosynthesis, its development continues to improve the quality of diagnostics and the therapy of breast cancer particularly for small breast cancer tumors or in neoadjuvant chemotherapy setting.

Ecomorphological correlates of twenty dominant fish species of Amazonian floodplain lakes / Correlações ecomorfológicas de vinte espécies de peixes dominantes em lagos de várzea da Amazônia

Abstract Fishes inhabiting Amazonian floodplain lakes exhibits a great variety of body shape, which was a key advantage to colonize the several habitats that compose these areas adjacent to the large Amazon rivers. In this paper, we did an ecomorphological analysis of twenty abundant species, sampled in May and August 2011, into two floodplain lakes of the lower stretch of the Solimões River. The analysis detected differences among species, which could be probably associated with swimming ability and habitat use preferences.

Resumo Os peixes que habitam os lagos de várzea da Amazônia apresentam morfologias bastante diversas, possibilitando a exploração bem sucedida dos diferentes habitats que formam estas áreas adjacentes aos grandes rios amazônicos. Neste artigo, relatamos os resultados de uma análise ecomorfológica de vinte espécies abundantes, coletadas em maio e agosto de 2011, em dois lagos das várzeas do trecho inferior do rio Solimões. As analises indicaram diferenças entre as espécies como função do atributos ecomorfológicos, provavelmente associadas com a capacidade natatória e com preferências por habitat.

Ecomorphological correlates of twenty dominant fish species of Amazonian floodplain lakes.

Fishes inhabiting Amazonian floodplain lakes exhibits a great variety of body shape, which was a key advantage to colonize the several habitats that compose these areas adjacent to the large Amazon rivers. In this paper, we did an ecomorphological analysis of twenty abundant species, sampled in May and August 2011, into two floodplain lakes of the lower stretch of the Solimões River. The analysis detected differences among species, which could be probably associated with swimming ability and habitat use preferences.

Senology in Gynaecology Specialist Training: a Baseline Survey from 2014.

Introduction: Qualified training in senology is essential for maintaining adequate, high quality patient care. In order to meet the needs of doctors in training and those of the medical infrastructure it is necessary to assess the quality of training regularly, to enable its adaption and optimisation. Methods: We developed a comprehensive, 10 item online questionnaire to assess the quality of specialised training in senology. This questionnaire was sent to 4000 speciality trainees and young specialists countrywide via the DGGG newsletter and was accessible for over four weeks. Results: 111 obstetrics and gynaecology speciality trainees participated in this national survey, 79 % of whom were female. 33 % of participants were working at university hospitals, 29 % at hospitals offering maximal level care without an associated medical faculty, 37 % at hospitals offering primary and secondary level care and 2 % at gynaecology practices. 25 % of participants could imagine working in the field of senology in future. On average the current perception of general specialist training was satisfactory. Specialist trainees at university hospitals rated training in senology highest (score: 2.95) compared to those at other hospitals. A fixed rotation through a breast centre offering comprehensive advanced training was seen as a potential improvement to senology training. Conclusions: This is the first survey of specialised training in senology to be conducted in Germany. Results showed that there is significant potential for young doctors to enter the speciality in future. There are also significant differences in the perceived quality of senology training between training facilities. This survey aimed to determine the quality of specialised training at senology centres and hopes to contribute to a sustainable improvement in training. The intention is to continue to make senology attractive to gynaecologists and to ensure well-grounded training.

Herbage intake, methane emissions and animal performance of steers grazing dwarf elephant grass v. dwarf elephant grass and peanut pastures.

Management strategies for increasing ruminant legume consumption and mitigating methane emissions from tropical livestock production systems require further study. The aim of this work was to evaluate the herbage intake, animal performance and enteric methane emissions of cattle grazing dwarf elephant grass (DEG) (Pennisetum purpureum cv. BRS Kurumi) alone or DEG with peanut (Arachis pintoi cv. Amarillo). The experimental treatments were the following: DEG pastures receiving nitrogen fertilization (150 kg N/ha as ammonium nitrate) and DEG intercropped with peanut plus an adjacent area of peanut that was accessible to grazing animals for 5 h/day (from 0700 to 1200 h). The animals grazing legume pastures showed greater average daily gain and herbage intake, and shorter morning and total grazing times. Daily methane emissions were greater from the animals grazing legume pastures, whereas methane emissions per unit of herbage intake did not differ between treatments. Allowing animals access to an exclusive area of legumes in a tropical grass-pasture-based system can improve animal performance without increasing methane production per kg of dry matter intake.

Touch Imprint Cytology and Stereotactically-Guided Core Needle Biopsy of Suspicious Breast Lesions: 15-Year Follow-up.

Introduction: Stereotactically-guided core needle biopsies (CNB) of breast tumours allow histological examination of the tumour without surgery. Touch imprint cytology (TIC) of CNB promises to be useful in providing same-day diagnosis for counselling purposes and for planning future surgery. Having addressed the issue of accuracy of immediate microscopic evaluation of TIC, we wanted to re-examine the usefulness of this procedure in light of the present health care climate of cost containment by incorporating the surgical 15-year follow-up data and outcome. Patients and Methods: From January until December 1996 we performed TIC in core needle biopsies of 173 breast tumours in 169 patients, consisting of 122 malignant and 51 benign tumours. Histology of core needle biopsies was proven by surgical histology in all malignant and in 5 benign tumours. Surgical breast biopsy was not performed in 46 patients with 46 benign lesions, as the histological result from the core needle biopsy and the result of the TIC were in agreement with the suspected diagnosis from the complementary breast diagnostics. A 15-year follow-up of these patients followed in 2013 and follow-up data was collected from 40 women. Results: In the 15-year follow-up of the 40 benign lesions primarily confirmed using CNB and TIC, a diagnostic sensitivity, specificity, positive and negative predictive value and accuracy of 100 % was found. Conclusion: TIC and stereotactically guided CNB showed excellent long-term follow-up in patients with benign breast lesions. The use of TIC to complement CNB can therefore provide immediate cytological diagnosis of breast lesions.

Single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (SAFE trial): a multicenter, open-label, randomized controlled trial.

OBJECTIVE: To determine whether the amniotic fluid index (AFI) or the single deepest vertical pocket (SDP) technique for estimating amniotic fluid volume is superior for predicting adverse pregnancy outcome. METHODS: This was a multicenter randomized controlled trial including 1052 pregnant women with a term singleton pregnancy across four hospitals in Germany. Women were assigned randomly, according to a computer-generated allocation sequence, to AFI or SDP measurement for estimation of amniotic fluid volume. Oligohydramnios was defined as AFI ≤ 5 cm or the absence of a pocket measuring at least 2 × 1 cm. The diagnosis of oligohydramnios was followed by labor induction. The primary outcome measure was postpartum admission to a neonatal intensive care unit. Further outcome parameters were the rates of diagnosis of oligohydramnios and induction of labor (for oligohydramnios or without specific indication), and mode of delivery. RESULTS: Postpartum admission to a neonatal intensive care unit was similar between groups (4.2% (n = 21) vs 5.0% (n = 25); relative risk (RR), 0.85 (95% CI, 0.48-1.50); P = 0.57). In the AFI group, there were more cases of oligohydramnios (9.8% (n = 49) vs 2.2% (n = 11); RR, 4.51 (95% CI, 2.2-8.57); P < 0.01) and more cases of labor induction for oligohydramnios (12.7% (n = 33) vs 3.6% (n = 10); RR, 3.50 (95% CI, 1.76-6.96); P < 0.01) than in the SDP group. Moreover, an abnormal cardiotocography was seen more often in the AFI group than in the SDP group (32.3% (n = 161) vs 26.2% (n = 132); RR, 1.23 (95% CI, 1.02-1.50); P = 0.03). The other outcome measures were not significantly different between the two groups. CONCLUSIONS: Use of the AFI method increased the rate of diagnosis of oligohydramnios and labor induction for oligohydramnios without improving perinatal outcome. The SDP method is therefore the favorable method to estimate amniotic fluid volume, especially in a population with many low-risk pregnancies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Comparison of Sonography versus Digital Breast Tomosynthesis to Locate Intramammary Marker Clips.

Introduction: This study aimed to compare the accuracy of sonography versus digital breast tomosynthesis to locate intramammary marker clips placed under ultrasound guidance. Patients and Methods: Fifty patients with suspicion of breast cancer (lesion diameter less than 2 cm [cT1]) had ultrasound-guided core needle biopsy with placement of a marker clip in the center of the tumor. Intramammary marker clips were subsequently located with both sonography and digital breast tomosynthesis. Results: Sonography detected no dislocation of intrammammary marker clips in 42 of 50 patients (84 %); dislocation was reported in 8 patients (16 %) with a maximum dislocation of 7 mm along the x-, y- or z-axis. Digital breast tomosynthesis showed accurate placement without dislocation of the intramammary marker clip in 48 patients (96 %); 2 patients (4 %) had a maximum clip dislocation of 3 mm along the x-, y- or z-axis (p < 0.05). Conclusion: The use of digital breast tomosynthesis could improve the accuracy when locating intramammary marker clips compared to sonography and could, in future, be used to complement or even completely replace sonography.

An outbreak of Salmonella Newport associated with mung bean sprouts in Germany and the Netherlands, October to November 2011.

The largest Salmonella enterica serovar Newport outbreak (n=106) ever reported in Germany occurred in October and November 2011. Twenty associated cases were reported in the Netherlands. The outbreak investigation included an analytical epidemiological study, molecular typing of human and food isolates and food traceback investigations. Unspecified Salmonella had been detected in samples of mung bean sprouts at a sprout producer (producer A) in the Netherlands and mung bean sprouts contaminated with S. Newport had been found during routine sampling at a sprout distributor in Germany. Therefore, we tested the hypothesis of sprouts being the infection vehicle. In a case-control study, we compared 50 notified adult S. Newport cases with 45 Salmonella enterica serovar Enteritidis cases regarding their food consumption in the three days before illness. In multivariable logistic regression analysis, only sprout consumption was significantly associated with S. Newport infection (odds ratio: 18.4; 95% confidence interval: 2.2-150.2). Molecular typing patterns of human isolates were indistinguishable from a mung bean sprouts isolate. Traceback of sprouts led to distributors and producer A in the Netherlands. Since sprouts are frequently contaminated with microorganisms, consumers need to be aware that consumption of raw or insufficiently cooked sprouts may pose a health risk.

Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study.

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1-5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5-10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information.

Is there a benefit to use calculated percent body fat or age- and gender-adjusted BMI-SDS(LMS) to predict risk factors for cardiovascular disease? A German/Austrian multicenter DPV-Wiss analysis on 42 048 type 2 diabetic patients.

OBJECTIVE: In clinical practice Body Mass Index is generally used to evaluate overweight status in adults. The present multicenter study examines whether Body Mass Index (BMI), age- and gender-adjusted Body Mass Index Standard Deviation Score, or calculated %body fat is a better predictor for cardiovascular disease risk factors, specifically hypertension and dyslipidemia, in a high-risk population. METHODS: Data of 42 048 adult type 2 diabetic patients (median age: 67.1 years) from 161 centers in Germany (n=158) and Austria (n=3) registered in a standardized, prospective, computer-based documentation program, were included in the study. For each patient body weight, height, blood pressure and blood lipids were documented. Spearman correlation analyses as well as multivariable logistic regression models were used to examine the relationship between anthropometric measurements and cardiovascular disease risk factors. RESULTS: Correlation and regression analyses revealed minor, non significant differences between the 3 anthropometric measurements (all p>0.05). In both genders, relationships between anthropometric measurements and hypertension or reduced HDL-cholesterol were nearly identical. Only for increased triglycerides, the relations with the 3 anthropometric measurements were significantly stronger in males than in females (p<0.0001, respectively). With increasing age, associations between anthropometric measurements and hypertension, reduced HDL-cholesterol or increased triglycerides became weaker. Spearman correlation coefficients for total cholesterol and LDL-cholesterol revealed weak associations with the 3 anthropometric measurements. CONCLUSION: Compared to Body Mass Index, age- and gender-adjusted Body Mass Index Standard Deviation Score, or calculation of %body fat, has no further benefit to predict cardiovascular disease risk factors in adult type 2 diabetic patients.

Radiotherapy with or without chemotherapy in the treatment of anal cancer: 20-year experience from a single institute.

PURPOSE: To report the efficacy and toxicity of radio(chemo)therapy (RCT) in the management of squamous cell anal carcinoma (SQ-AC) and to evaluate the prognostic factors influencing the outcomes. PATIENTS AND METHODS: A consecutive cohort of 138 patients with cT1-4, cN0-3, cM0 SQ-AC were treated with RCT between 1988 and 2011 at our department. Median follow-up time for surviving patients from the start of RCT was 98 months (range, 1-236 months). Patients were treated with a median radiation dose of 56 Gy (range, 4-61 Gy). Concurrent chemotherapy was administered to 119 patients (86%). RESULTS: The survival rates at 2, 5, and 10 years were 88 ± 3, 82 ± 4, and 59 ± 6%, respectively, with a median overall survival (OS) of 167 months. The cumulative incidence for local recurrence at 2 and 5 years was 8 ± 2 and 11 ± 3%, respectively. The median disease-free survival (DFS) and colostomy-free survival (CFS) times were 132 and 135 months, respectively. In 19 patients (14%), a distant metastasis was diagnosed after a median time of 19 months. In the multivariate analysis, UICC (International Union Against Cancer) stage I-II, female gender, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and good/moderate histologic differentiation (G1-2) were significantly associated with a better OS, DFS, and CFS. Conformal radiotherapy planning techniques were significantly associated with a lower cumulative incidence of local recurrence (11 ± 3% vs. 38 ± 19% at 5 years, p = 0.006). A higher radiation dose beyond 54 Gy was not associated with an improvement in outcome, neither for smaller-(T1/T2) nor for larger tumors (T3/T4). CONCLUSION: RCT leads to excellent outcomes-especially in patients with stage I/II and G1/G2 tumors-with acceptable toxicity. The probable advantages of high-dose radiotherapy should be considered carefully against the risk of a higher rate of toxicity. Future studies are needed to investigate the role of a more intensified (systemic) treatment for patients with unfavorable prognostic factors such as T3/T4, N+, and/or poor cell differentiation.

Evaluation of Newly Adapted Clip Marker System in Ultrasound-Guided Core Needle Biopsy for Suspicion of Breast Cancer.

Introduction: A newly adapted clip system for intramammary marking during ultrasound-guided core needle biopsy for suspicion of breast cancer is described and evaluated here. Material and Method: Fifty patients with suspicion of breast cancer (cT2) had ultrasound-guided core needle biopsy using a newly adapted clip marker system (HistoCore™ and O-Twist Marker™). Subsequently, ultrasound follow-up and tomosynthesis scans were done to determine the location of the marker clips. Results: No dislocation of the marker clip was detected on ultrasound in 45 of 50 patients (90 %), and 5 patients (10 %) had a maximum dislocation of 5 mm along the x-, y- or z-axis. Tomosynthesis scans demonstrated precise placement without dislocation of the clip markers in 48 patients (96 %); 2 patients (4 %) had a maximum dislocation of 3 mm along the x-, y- or z-axis. Conclusion: The newly developed clip marker system, a combination of a single-use breast biopsy needle and a precise, length-adapted intramammary marker clip, represents a further improvement in oncological therapy. This is of particular importance for patients requiring subsequent neoadjuvant chemotherapy, as in cases with complete tumour remission, there is no target point for preoperative, ultrasound-guided wire marking.

Breast Cancer Risk - From Genetics to Molecular Understanding of Pathogenesis.

Several advancements over the last decade have triggered the developments in the field of breast cancer risk research. One of them is the availability of the human genome sequence along with cheap genotyping possibilities. Another is the globalization of research, which has led to the growth of research collaboration into large international consortia that facilitate the pooling of clinical and genotype data of hundreds of thousands of patients and healthy control individuals. This review concerns with the recent developments in breast cancer risk research and focuses on the discovery of new genetic breast cancer risk factors and their meaning in the context of established non-genetic risk factors. Finally the clinical application is highly dependent on the accuracy of breast cancer risk prediction models, not only for all breast cancer patients, but also for molecular subtypes, preferably for those which are associated with an unfavorable prognosis. Recently risk prediction incorporates all possible risk factors, which include epidemiological risk factors, mammographic density and genetic risk factors.

Full Field Digital Mammography (FFDM) versus CMOS Technology, Specimen Radiography System (SRS) and Tomosynthesis (DBT) - Which System Can Optimise Surgical Therapy?

Aim: This prospective clinical study aimed to evaluate whether it would be possible to reduce the rate of re-excisions using CMOS technology, a specimen radiography system (SRS) or digital breast tomosynthesis (DBT) compared to a conventional full field digital mammography (FFDM) system. Material and Method: Between 12/2012 and 2/2013 50 patients were diagnosed with invasive breast cancer (BI-RADS™ 5). After histological verification, all patients underwent breast-conserving therapy with intraoperative imaging using 4 different systems and differing magnifications: 1. Inspiration™ (Siemens, Erlangen, Germany), amorphous selenium, tungsten source, focus 0.1 mm, resolution 85 µm pixel pitch, 8 lp/mm; 2. BioVision™ (Bioptics, Tucson, AZ, USA), CMOS technology, photodiode array, flat panel, tungsten source, focus 0.05, resolution 50 µm pixel pitch, 12 lp/mm; 3. the Trident™ specimen radiography system (SRS) (Hologic, Bedford, MA, USA), amorphous selenium, tungsten source, focus 0.05, resolution 70 µm pixel pitch, 7.1 lp/mm; 4. tomosynthesis (Siemens, Erlangen, Germany), amorphous selenium, tungsten source, focus 0.1 mm, resolution 85 µm pixel pitch, 8 lp/mm, angular range 50 degrees, 25 projections, scan time > 20 s, geometry: uniform scanning, reconstruction: filtered back projection. The 600 radiographs were prospectively shown to 3 radiologists. Results: Of the 50 patients with histologically proven breast cancer (BI-RADS™ 6), 39 patients required no further surgical therapy (re-excision) after breast-conserving surgery. A retrospective analysis (n = 11) showed a significant (p < 0.05) increase of sensitivity with the BioVision™, the Trident™ and tomosynthesis compared to the Inspiration™ at a magnification of 1.0 : 2.0 or 1.0 : 1.0 (tomosynthesis) (2.6, 3.3 or 3.6 %), i.e. re-excision would not have been necessary in 2, 3 or 4 patients, respectively, compared to findings obtained with a standard magnification of 1.0 : 1.0. Conclusion: The sensitivity of the BioVision™, the Trident™ and tomosynthesis was significantly (p < 0.05) higher and the rate of re-excisions was reduced compared to FFDM using a conventional detector at a magnification of 2.0 but without zooming.