28 research outputs found

    Breast cancer metastasis to gynaecological organs: a clinico-pathological and molecular profiling study

    Get PDF
    Breast cancer metastasis to gynaecological organs is an understudied pattern of tumour spread. We explored clinico-pathological and molecular features of these metastases to better understand whether this pattern of dissemination is organotropic or a consequence of wider metastatic dissemination. Primary and metastatic tumours from 54 breast cancer patients with gynaecological metastases were analysed using immunohistochemistry, DNA copy-number profiling, and targeted sequencing of 386 cancer-related genes. The median age of primary tumour diagnosis amongst patients with gynaecological metastases was significantly younger compared to a general breast cancer population (46.5 versus 60 years; p < 0.0001). Median age at metastatic diagnosis was 54.4, time to progression was 4.8 years (range 0-20 years), and survival following a diagnosis of metastasis was 1.95 years (range 0-18 years). Patients had an average of five involved sites (most frequently ovary, fallopian tube, omentum/peritoneum), with fewer instances of spread to the lungs, liver, or brain. Invasive lobular histology and luminal A-like phenotype were over-represented in this group (42.8 and 87.5%, respectively) and most patients had involved axillary lymph nodes (p < 0.001). Primary tumours frequently co-expressed oestrogen receptor cofactors (GATA3, FOXA1) and harboured amplifications at 8p12, 8q24, and 11q13. In terms of phenotype conversion, oestrogen receptor status was generally maintained in metastases, FOXA1 increased, and expression of progesterone receptor, androgen receptor, and GATA3 decreased. ESR1 and novel AR mutations were identified. Metastasis to gynaecological organs is a complication frequently affecting young women with invasive lobular carcinoma and luminal A-like breast cancer, and hence may be driven by sustained hormonal signalling. Molecular analyses reveal a spectrum of factors that could contribute to de novo or acquired resistance to therapy and disease progression.Jamie R Kutasovic, Amy E McCart Reed, Renique Males, Sarah Sim, Jodi M Saunus ... Liana Dedina ... et al

    Information-theoretical Limits of Recursive Estimation and Closed-loop Control in High-contrast Imaging

    No full text
    A lower bound on unbiased estimates of wave front errors (WFEs) is presented for the linear regime of small perturbation and active control of a high-contrast region (dark hole). Analytical approximations and algorithms for computing the closed-loop covariance of the WFE modes are provided for discrete- and continuous-time linear WFE dynamics. Our analysis applies to both image-plane and non-common-path wave front sensing (WFS) with Poisson-distributed measurements and noise sources (i.e., photon-counting mode). Under this assumption, we show that recursive estimation benefits from infinitesimally short exposure times, is more accurate than batch estimation and, for high-order WFE drift dynamical processes, scales better than batch estimation with amplitude and star brightness. These newly derived contrast scaling laws are a generalization of previously known theoretical and numerical results for turbulence-driven adaptive optics. For space-based coronagraphs, we propose a scheme for combining models of WFE drift, low-order non-common-path WFS (LOWFS) and high-order image-plane WFS (HOWFS) into closed-loop contrast estimates. We also analyze the impact of residual low-order WFE, sensor noise, and other sources incoherent with the star, on closed-loop dark hole maintenance and the resulting contrast. As an application example, our model suggests that the Roman Space Telescope might operate in a regime that is dominated by incoherent sources rather than WFE drift, where the WFE drift can be actively rejected throughout the observations with residuals significantly dimmer than the incoherent sources. The models proposed in this paper make possible the assessment of the closed-loop contrast of coronagraphs with combined LOWFS and HOWFS capabilities, and thus help estimate WFE stability requirements of future instruments. © 2021. The American Astronomical Society. All rights reserved.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
    corecore