Re-evaluation of HER2 status in metastatic breast cancer and tumor-marker guided therapy with vinorelbine and trastuzumab

Background: HER2 is overexpressed in 20 - 30% of breast cancers. Compared to chemotherapy alone, chemotherapy with trastuzumab improves clinical outcome in patients with HER2- positive metastatic breast cancer ( MBC). In general, HER2 status in a primary lesion predicts the status of metastases, so that biopsy of metastatic lesions appears unnecessary. Case Report: A 39- year old woman was diagnosed with primary breast cancer in November 2000. Using the method and scoring system of the DAKO Hercep Test, the tumor has shown low HER2 expression ( DAKO score 1+). After failure of several chemotherapy regimens for metastatic disease ( liver, skeletal), the patient underwent CT- guided needle biopsy of the liver which showed HER2 positive adenocarcinoma ( DAKO score 3+). In consequence, the patient was treated with vinorelbine ( 30 mg/ m(2) d1,8,15 q4w) and trastuzumab ( 4 mg/ kg loading dose, 2 mg/ kg weekly). During a treatment period of 4 months imaging results as well as tumor marker kinetics indicated an excellent response with sustained decrease of tumor markers. A retrospective analysis of the HER2 shed antigen in metastatic stage revealed excessively increased serum levels and supports HER2 overexpression observed in liver metastasis. The kinetics of the HER2 shed antigen during therapy for metastatic disease were found to be in phase with the kinetics of CEA and CA15- 3. Conclusion: This case report demonstrates that re- evaluation of the HER2 status may be helpful in single patients not sufficiently responding to treatment of metastatic disease. Determination of HER2 overexpression may be facilitated by a determination of the HER2 shed antigen level in peripheral blood

Evolutionary games and quasispecies

We discuss a population of sequences subject to mutations and frequency-dependent selection, where the fitness of a sequence depends on the composition of the entire population. This type of dynamics is crucial to understand the evolution of genomic regulation. Mathematically, it takes the form of a reaction-diffusion problem that is nonlinear in the population state. In our model system, the fitness is determined by a simple mathematical game, the hawk-dove game. The stationary population distribution is found to be a quasispecies with properties different from those which hold in fixed fitness landscapes.Comment: 7 pages, 2 figures. Typos corrected, references updated. An exact solution for the hawks-dove game is provide

General Upper Bounds on the Runtime of Parallel Evolutionary Algorithms

We present a general method for analyzing the runtime of parallel evolutionary algorithms with spatially structured populations. Based on the fitness-level method, it yields upper bounds on the expected parallel runtime. This allows for a rigorous estimate of the speedup gained by parallelization. Tailored results are given for common migration topologies: ring graphs, torus graphs, hypercubes, and the complete graph. Example applications for pseudo-Boolean optimization show that our method is easy to apply and that it gives powerful results. In our examples the performance guarantees improve with the density of the topology. Surprisingly, even sparse topologies such as ring graphs lead to a significant speedup for many functions while not increasing the total number of function evaluations by more than a constant factor. We also identify which number of processors lead to the best guaranteed speedups, thus giving hints on how to parameterize parallel evolutionary algorithms

Ground-States of Two Directed Polymers

Joint ground states of two directed polymers in a random medium are investigated. Using exact min-cost flow optimization the true two-line ground-state is compared with the single line ground state plus its first excited state. It is found that these two-line configurations are (for almost all disorder configurations) distinct implying that the true two-line ground-state is non-separable, even with 'worst-possible' initial conditions. The effective interaction energy between the two lines scales with the system size with the scaling exponents 0.39 and 0.21 in 2D and 3D, respectively.Comment: 19 pages RevTeX, figures include

On Growth, Disorder, and Field Theory

This article reviews recent developments in statistical field theory far from equilibrium. It focuses on the Kardar-Parisi-Zhang equation of stochastic surface growth and its mathematical relatives, namely the stochastic Burgers equation in fluid mechanics and directed polymers in a medium with quenched disorder. At strong stochastic driving -- or at strong disorder, respectively -- these systems develop nonperturbative scale-invariance. Presumably exact values of the scaling exponents follow from a self-consistent asymptotic theory. This theory is based on the concept of an operator product expansion formed by the local scaling fields. The key difference to standard Lagrangian field theory is the appearance of a dangerous irrelevant coupling constant generating dynamical anomalies in the continuum limit.Comment: review article, 50 pages (latex), 10 figures (eps), minor modification of original versio

Directed polymers in high dimensions

We study directed polymers subject to a quenched random potential in d transversal dimensions. This system is closely related to the Kardar-Parisi-Zhang equation of nonlinear stochastic growth. By a careful analysis of the perturbation theory we show that physical quantities develop singular behavior for d to 4. For example, the universal finite size amplitude of the free energy at the roughening transition is proportional to (4-d)^(1/2). This shows that the dimension d=4 plays a special role for this system and points towards d=4 as the upper critical dimension of the Kardar-Parisi-Zhang problem.Comment: 37 pages REVTEX including 4 PostScript figure

Quantized Scaling of Growing Surfaces

The Kardar-Parisi-Zhang universality class of stochastic surface growth is studied by exact field-theoretic methods. From previous numerical results, a few qualitative assumptions are inferred. In particular, height correlations should satisfy an operator product expansion and, unlike the correlations in a turbulent fluid, exhibit no multiscaling. These properties impose a quantization condition on the roughness exponent $\chi$ and the dynamic exponent $z$. Hence the exact values $\chi = 2/5, z = 8/5$ for two-dimensional and $\chi = 2/7, z = 12/7$ for three-dimensional surfaces are derived.Comment: 4 pages, revtex, no figure

Vicinal Surfaces and the Calogero-Sutherland Model

A miscut (vicinal) crystal surface can be regarded as an array of meandering but non-crossing steps. Interactions between the steps are shown to induce a faceting transition of the surface between a homogeneous Luttinger liquid state and a low-temperature regime consisting of local step clusters in coexistence with ideal facets. This morphological transition is governed by a hitherto neglected critical line of the well-known Calogero-Sutherland model. Its exact solution yields expressions for measurable quantities that compare favorably with recent experiments on Si surfaces.Comment: 4 pages, revtex, 2 figures (.eps

New Criticality of 1D Fermions

One-dimensional massive quantum particles (or 1+1-dimensional random walks) with short-ranged multi-particle interactions are studied by exact renormalization group methods. With repulsive pair forces, such particles are known to scale as free fermions. With finite $m$-body forces (m = 3,4,...), a critical instability is found, indicating the transition to a fermionic bound state. These unbinding transitions represent new universality classes of interacting fermions relevant to polymer and membrane systems. Implications for massless fermions, e.g. in the Hubbard model, are also noted. (to appear in Phys. Rev. Lett.)Comment: 10 pages (latex), with 2 figures (not included