ASCO 2007: What remains important for breast cancer systemic therapy in the routine setting?

The 43rd ASCO Annual Meeting took place from June 1-5, 2007 at McCormick Place in Chicago, IL, USA. This year's meeting had the special theme of `Translating Research into Practice', particularly featuring 445 abstracts on translational research in addition to approximately 2,000 abstracts presented on subjects like surgery, radiation therapy, chemotherapy, endocrine therapy, and targeted therapies. This short summary will focus on the two important breast cancer oral presentation sessions only, and will try to comment on the presented data with regard to their immediate impact on clinical practice. Many more research results regarding breast cancer were presented (all presentations will be available to the public from September 1, 2007 at wwwasco.org). In general, breast cancer data presented at this year's ASCO Annual Meeting confirmed current standards, and introduced promising new substances which may soon enter clinical practice. The 44th ASCO Annual Meeting will again be held in Chicago from May 30 to June 3, 2008. Those who do not want to wait another year may visit ASCO's first special Breast Cancer Symposium taking place September 7-8, 2007 in San Francisco, CA, USA. Whether this meeting will start a new tradition of a specialized ASCO breast cancer symposium, and how this development will eventually will impact on the regular San Antonio Breast Cancer Symposium in December, only time will tell

Anisotropic backscatter in ice-penetrating radar data: potential mechanisms and implications

Airborne and ground-based radar have been used extensively in the past to measure ice thickness and to investigate the internal structure of ice sheets in terms of layering. The main reflection mechanisms for internal reflections are changes in density, conductivity, and crystal orientation fabric, which alter thepermittivity of the ice. Linking the different mechanisms to the individual reflection horizons enables thededuction of glaciological parameters like accumulation rates or age-depth estimates. If no sample material from snow pits or ice-cores are available, multi-frequency and multi-polarization measurements must be applied to distinguish between the different reflection mechanisms. The backscattered power of horizons caused by changes in conductivity varies with the center frequency whereas in the case of horizons originating from changing crystal orientation the backscattered power is dependent on the polarization plane of the carrier signal.In this study we examine a sample data set near the German summer station Kohnen (drill site for theEPICA-EDML ice core) on the Antarctic plateau. The data were acquired with an airplane sliding on ground, producing varying incident polarization with a circular profile and several cross profiles with different headings. We find that the backscattered power changes with varying antenna orientation (i.e. polarization). In the upper third of the ice column the backscatter has two maxima with a 180° symmetry. The maxima align with the direction of minimal surface strain. At approximately 900 m depth the anisotropy is shifted by 90° in heading azimuth, with the maxima now being parallel to the maximum in surface strain. This dataset is unique, as airborne systems (primarily designed for the sounding of ice thickness) are usually not used for ground-based applications. The observed anisotropy appears clearly and is intriguing as the reason for it is entirely unknown. As primary suspects we consider the role of changing crystal orientation and ellipsoidal shaped air bubbles. The effect is visible from 200 1400 m. It appears distributed along the entire interval, and not restricted to individual layers. It seems that the polarization dependence becomes visible by a changing background level of the acquired signal, which is otherwise largely dominated by layer-like, polarization independent reflections. Hence we apply a (semi-analytical) volume scattering model in order to understand the different reflection mechanisms better. From ice-core measurements it is known that the crystals in the upper hundred meters are only weakly aligned (if at all), and it is unclear how the crystal orientation changes overshort depth intervals (~10 m). The rotation of the anisotropy coincides with the clathrate transition in the ice core and thus we first focus on the effect of anisotropic air bubbles. In an in-coherent approach we treat the ice matrix as a random medium and use the vector radiative transfer theory to incorporate boundary conditions. In a second step we model the effect of crystal orientation to estimate both, the degree of alignment and the statistical variance in the permittivity tensor needed to generate the observed pattern in backscatter. Doing so, we eventually aim at pinning down the mechanisms for the anisotropy in the upper interval, lower interval and the interrelation of the two by a shift of 90°.Anisotropic air bubbles as well as aligned crystal orientation allow to deduce stress and strain rates and a potential change thereof along depth. So far it is largely unclear, how surface strain rates relate with strain rates within the ice. If one of the two suspected mechanisms can be excluded or confirmed, this study may serve as a case study for future polarimetric surveys with low-frequency radars, in order to supply ice-sheet modelling with adequate boundary conditions - including changes in the internal structure of ice sheets along depth

Node-positive breast cancer: Which are the best chemotherapy regimens?

Breast cancer-associated mortality has been significantly reduced since the 1990s, mainly because of early diagnosis and systemic therapeutic interventions. All three therapy components-cytostatic therapy, endocrine therapy and targeted antibody therapy-are at present necessary tools for the curative treatment of primary breast cancer. This article reviews the evidence base for the use of various chemotherapy schedules in patients with primary, node-positive breast cancer, including schedules in combination with targeted HER2/neu therapy

Monitoring in metastatic breast cancer: Is imaging outdated in the era of circulating tumor cells?

In clinical practice imaging technologies such as computed tomography (CT), positron emission tomography (PET)/CT and magnetic resonance imaging (MRI) are well-established methods for monitoring metastatic breast cancer (MBC) patients and for assessing therapeutic efficacy. However, several weeks of treatment are required before these technologies can offer any reliable information on effective disease regression, and, in the meanwhile, the patients are exposed to potentially unnecessary therapy. Circulating tumor cells (CTCs) have been shown to be powerful prognostic and predictive markers and provide clinicians with valuable information. However, in one clinical trial, an early change of chemotherapy based on CTC detection did not result in improved survival. Currently, CTC detection outside clinical trials should be limited to selected clinical situations, i.e. increased treatment toxicity or as risk estimation

Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer

Introduction: MicroRNAs (miRs) are interesting new diagnostic targets that may provide important insights into the molecular pathogenesis of breast cancer. Here we evaluated, for the first time, the feasibility and clinical utility of circulating miRs as biomarkers for the detection and staging of breast cancer. Methods: The relative concentrations of breast cancer-associated miR10b, miR34a, miR141 and miR155 were measured in the blood serum of 89 patients with primary breast cancer (M0, n = 59) and metastatic disease (M1, n = 30), and 29 healthy women by a TaqMan MicroRNA Assay. Results: The relative concentrations of total RNA (P = 0.0001) and miR155 (P = 0.0001) in serum significantly discriminated M0-patients from healthy women, whereas miR10b (P = 0.005), miR34a (P = 0.001) and miR155 (P = 0.008) discriminated M1-patients from healthy controls. In breast cancer patients, the changes in the levels of total RNA (P = 0.0001), miR10b (P = 0.01), miR34a (P = 0.003) and miR155 (P = 0.002) correlated with the presence of overt metastases. Within the M0-cohort, patients at advanced tumor stages (pT3 to 4) had significantly more total RNA (P = 0.0001) and miR34a (P = 0.01) in their blood than patients at early tumor stages (pT1 to 2). Conclusions: This pilot study provides first evidence that tumor-associated circulating miRs are elevated in the blood of breast cancer patients and associated with tumor progression

Impact of marine processes on flow dynamics of northern Antarctic Peninsula outlet glaciers

ARISING FROM P. A. Tuckett et al., Nature Communications https://doi.org/10.1038/s41467-019-12039-2 (2019)

Toxicity Analysis in the ADEBAR Trial: Sequential Anthracycline-Taxane Therapy Compared with FEC120 for the Adjuvant Treatment of High-Risk Breast Cancer

Background: Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer. Patients and Methods: The ADEBAR trial was a multicenter phase Ill trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4x epirubicin (90 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 3 weeks (q3w), followed by 4x docetaxel (100 mg/m(2)) q3w (EC-Doc arm), or 6x epirubicin (60 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1 and 8 and cyclophosphamide (75 mg/m(2)) on days 1-14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility. Results: Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009). Conclusion: The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy

Basal conditions of two Transantarctic Mountains outlet glaciers from observation-constrained diagnostic modelling

This is the published version. Copyright 2014 International Glaciological SocietyWe present a diagnostic glacier flowline model parameterized and constrained by new velocity data from ice-surface GPS installations and speckle tracking of TerraSAR-X satellite images, newly acquired airborne-radar data, and continental gridded datasets of topography and geothermal heat flux, in order to better understand two outlet glaciers of the East Antarctic ice sheet. Our observational data are employed as primary inputs to a modelling procedure that first calculates the basal thermal regime of each glacier, then iterates the basal sliding coefficient and deformation rate parameter until the fit of simulated to observed surface velocities is optimized. We find that the two glaciers have both frozen and thawed areas at their beds, facilitating partial sliding. Glacier flow arises from a balance between sliding and deformation that fluctuates along the length of each glacier, with the amount of sliding typically varying by up to two orders of magnitude but with deformation rates far more constant. Beardmore Glacier is warmer and faster-flowing than Skelton Glacier, but an up-glacier deepening bed at the grounding line, coupled with ice thicknesses close to flotation, lead us to infer a greater vulnerability of Skelton Glacier to grounding-line recession if affected by ocean-forced thinning and concomitant acceleration

Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression

<p>Abstract</p> <p>Background</p> <p>As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases.</p> <p>Methods</p> <p>The concentrations of cell-free DNA and nucleosomes as well as the protease and caspase activities were measured in serum of patients with benign breast disease (n = 20), primary breast cancer (M0, n = 31), metastatic breast cancer (M1, n = 32), and healthy individuals (n = 28) by PicoGreen, Cell Death Detection ELISA, Protease Fluorescent Detection Kit and Caspase-Glo^®3/7 Assay, respectively.</p> <p>Results</p> <p>Patients with benign and malignant tumors had significantly higher levels of circulating nucleic acids in their blood than healthy individuals (p = 0.001, p = 0.0001), whereas these levels could not discriminate between benign and malignant lesions. Our analyses of all serum samples revealed significant correlations of circulating nucleosome with DNA concentrations (p = 0.001), nucleosome concentrations with caspase activities (p = 0.008), and caspase with protease activities (p = 0.0001). High serum levels of protease and caspase activities associated with advanced tumor stages (p = 0.009). Patients with lymph node-positive breast cancer had significantly higher nucleosome levels in their blood than node-negative patients (p = 0.004). The presence of distant metastases associated with a significant increase in serum nucleosome (p = 0.01) and DNA levels (p = 0.04), and protease activities (p = 0.008).</p> <p>Conclusion</p> <p>Our findings demonstrate that high circulating nucleic acid concentrations in blood are no indicators of a malignant breast tumor. However, the observed changes in apoptosis-related deregulation of proteolytic activities along with the elevated serum levels of nucleosomes and DNA in blood are linked to breast cancer progression.</p

Differential interferometric synthetic aperture radar for tide modelling in Antarctic ice-shelf grounding zones

Differential interferometric synthetic aperture radar (DInSAR) is an essential tool for detecting ice-sheet motion near Antarctica's oceanic margin. These space-borne measurements have been used extensively in the past to map the location and retreat of ice-shelf grounding lines as an indicator for the onset of marine ice-sheet instability and to calculate the mass balance of ice sheets and individual catchments. The main difficulty in interpreting DInSAR is that images originate from a combination of several SAR images and do not indicate instantaneous ice deflection at the times of satellite data acquisitions. Here, we combine the sub-centimetre accuracy and spatial benefits of DInSAR with the temporal benefits of tide models to infer the spatio-temporal dynamics of ice–ocean interaction during the times of satellite overpasses. We demonstrate the potential of this synergy with TerraSAR-X data from the almost-stagnant southern McMurdo Ice Shelf (SMIS). We then validate our algorithm with GPS data from the fast-flowing Darwin Glacier, draining the Antarctic Plateau through the Transantarctic Mountains into the Ross Sea. We are able to reconstruct DInSAR-derived vertical displacements to 7 mm mean absolute residual error and generally improve traditional tide-model output by up to 39 % from 10.8 to 6.7 cm RMSE against GPS data from areas where ice is in local hydrostatic equilibrium with the ocean and by up to 74 % from 21.4 to 5.6 cm RMSE against GPS data in feature-rich coastal areas where tide models have not been applicable before. Numerical modelling then reveals Young's modulus of E=1.0±0.56  GPa and an ice viscosity of ν=10±3.65  TPa s when finite-element simulations of tidal flexure are matched to 16 d of tiltmeter data, supporting the hypothesis that strain-dependent anisotropy may significantly decrease effective viscosity compared to isotropic polycrystalline ice on large spatial scales. Applications of our method include the following: refining coarsely gridded tide models to resolve small-scale features at the spatial resolution and vertical accuracy of SAR imagery, separating elastic and viscoelastic contributions in the satellite-derived flexure measurement, and gaining information about large-scale ice heterogeneity in Antarctic ice-shelf grounding zones, the missing key to improving current ice-sheet flow models. The reconstruction of the individual components forming DInSAR images has the potential to become a standard remote-sensing method in polar tide modelling. Unlocking the algorithm's full potential to answer multi-disciplinary research questions is desired and demands collaboration within the scientific community