FISH testing of HER2 IHC 1+ early breast cancer with unfavorable prognostic factors

FISH testing of HER2 IHC 1+ early breast cancer with unfavorable prognostic factors Background HER2-positive tumors are associated with a poor prognosis and a shortened disease-free and overall survival as well as with other unfavorable prognostic tumor characteristics (high histological grade, high proliferative index, negative or low estrogen receptor expression, etc.). HER2-positive tumors are also responsive to treatment with trastuzumab in reducing the risk of recurrence and improving survival. The aim of this study is to assess the incidence of HER2 gene amplification in selected tumors with adverse prognostic features which scored 1+ by immunohistochemistry (IHC). Methods 75 women with infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) scoring 1+ by IHC were included. Forty-eight invasive breast carcinoma samples were selected according to unfavorable prognostic tumor characteristics and tested by FISH. HER2 amplification was evaluated using Vysis HER2/Cep17 probe (Path Vysion HER2 DNA Probe Kit®, Abbott Molecular, IL); ratio–based amplification was considered present when the HER2/Cep17 ratio was 2 or more and copy number-based amplification was considered present when the mean HER2 copy number was more than 6, in agreement with the ASCO/CAP/SIAPEC guidelines. Results In 2013, 331 patients with invasive breast tumors were tested by IHC; 75 cases (23%) were scored 1+ of which 62 cases (19%) of IDC and 13 cases (4%) of ILC. Forty-eight invasive breast carcinoma samples (64%) were selected according to one or more unfavorable prognostic tumor characteristics; 22 out of 48 tumors (46%) showed high histological grade (G3); 27 cases (56%) had high proliferative index (Ki-67≥30%); 32 tumor samples (67%) were node-positive; and 29 cases (60%) showed vascular invasion. FISH was performed on 31 of the 1+ patients with adverse tumor characteristics and 7 IDC out of 48 (14.6%) showed HER2 amplification. Conclusions Our preliminary retrospective data suggest that 7 patients out of 48 (14.6%) scoring 1+ by IHC show HER2 amplification, in agreement with the most recently published literature data. In order to not deny the benefit deriving from trastuzumab administration, in breast cancer patients showing IHC 1+, it is advisable to test HER2 gene amplification by FISH. Bibliografia Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, Dal Lago L, McFadden E, Dowsett M, Untch M, Gianni L, Bell R, Köhne CH, Vindevoghel A, Andersson M, Brunt AM, Otero-Reyes D, Song S, Smith I, Leyland-Jones B, Baselga J; Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013 Sep 21;382(9897):1021-8. Iorfida M, Dellapasqua S, Bagnardi V, Cardillo A, Rotmensz N, Mastropasqua MG, Bottiglieri L, Goldhirsch A, Viale G, Colleoni M. HER2-negative (1+) breast cancer with unfavorable prognostic features: to FISH or not to FISH? Ann Oncol. 2012 May;23(5):1371-2. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84

Classification and Management of Pontecerebellar-Petrosal Bridging Veins

The risks and benefits of coagulating intradural venous elements during a retrosigmoid approach for trigeminal neurovascular decompression has not been accurately established. The objectives of this study were to identify the veins that drain into the superior petrosal sinus, classify them in relation to the suprameatal tubercle, and determine the implication of their coagulation

Optic Foraminotomy for Clipping of Superior Carotid-Ophthalmic Aneurysms

Background: Carotid-ophthalmic aneurysms usually cause visual problems. Its surgical treatment is challenging because of its anatomically close relations to the optic nerve, carotid artery, ophthalmic artery, anterior clinoid process, and cavernous sinus, which hinder direct access. Despite recent technical advancements enabling risk reduction of this complication, postoperative deterioration of visual function remains a significant problem. Therefore, the goal of preserving and/or improving the visual outcome persists as a paramount concern. Objective: We propose optic foraminotomy as an alternative microsurgical technique for dorsal carotid-ophthalmic aneurysms clipping. As a secondary objective, the step by step of that technique and its benefits are compared to the current approach of anterior clinoidectomy. Methods: We present as an example two patients with superior carotid-ophthalmic aneurysms in which the standard pterional craniotomy, transsylvian approach, and optic foraminotomy were performed. Surgical techniques are presented and discussed in detail with the use of skull base dissections, microsurgical images, and original drawings. Results: Extensive opening of the optic canal and optic nerve sheath was successfully achieved in all patients allowing a working angle with the carotid artery for correct visualization of the aneurysm and further clipping. Significant visual acuity improvement occurred in both patients because of decompression of the optic nerve. Conclusion: Optic foraminotomy is an easy and recommended technique for exposing and treating superior carotid-ophthalmic aneurysms and allowing optic nerve decompression during the first stages of the procedure. It shows several advantages over the current anterior clinoidectomy technique regarding surgical exposure and facilitating visual improvement

Phosphate modified screen printed electrodes by lift treatment for glucose detection

The design of new materials as active layers is important for electrochemical sensor and biosensor development. Among the techniques for the modification and functionalization of electrodes, the laser induced forward transfer (LIFT) has emerged as a powerful physisorption method for the deposition of various materials (even labile materials like enzymes) that results in intimate and stable contact with target surface. In this work, Pt, Au, and glassy carbon screen printed electrodes (SPEs) treated by LIFT with phosphate buffer have been characterized by scanning electron microscopy and atomic force microscopy to reveal a flattening effect of all surfaces. The electrochemical characterization by cyclic voltammetry shows significant differences depending on the electrode material. The electroactivity of Au is reduced while that of glassy carbon and Pt is greatly enhanced. In particular, the electrochemical behavior of a phosphate LIFT treated Pt showed a marked enrichment of hydrogen adsorbed layer, suggesting an elevated electrocatalytic activity towards glucose oxidation. When Pt electrodes modified in this way were used as an effective glucose sensor, a 1–10 mM linear response and a 10 µM detection limit were obtained. A possible role of phosphate that was securely immobilized on a Pt surface, as evidenced by XPS analysis, enhancing the glucose electrooxidation is discussed

Coexistence of an imbalance of cytokines, chemokines and growth factors serum levels and symptoms of fatigue and pain in long-term breast cancer survivors.

Background: Fatigue, pain and depression are common problems among long-term cancer survivors (BCS) which in some patients may persist for many years after healing and the completion of treatment. Several studies have reported that increased serum levels of chemokines and growth factors are particularly significantly correlated with the coexistence of these disorders in cancer survivors. The aim of this study was to assess whether the altered imbalance of pro-inflammatory cytokines, growth factors and chemokine serum levels are associated to presence of fatigue and pain in long-term breast cancer survivors . Methods: Ninety-three BCS were enrolled in this study and blood samples taken from each. Serum levels of 25 analytes including cytokines, growth factors and chemokines were tested by enzyme immunoassay using the flexible Bio-Plex System. Participants also completed a questionnaire measuring demographic, clinical and behavioral variables. Results: Non-parametric discriminant analysis showed that fatigued BCS had significantly higher serum levels of FGF and lower IL-4 and IL-8 compared to the non-fatigued group, while BCS with pain had an increase in eotaxin serum levels and lower IL-4 and Il-7 compared to the group without pain. Univariate analysis showed a statistically significant difference in both mental and physical qol, with levels lower in the subgroup who presented pain than in those without: p = 0.0003 and p < 0.0001 respectively. A lower value of Rantes (p = 0.0131) in breast cancer survivors with pain compared to the group without pain, and a higher median value of TNF-α (p = 0.054) in the pain group than in those without pain was observed. The level of depression was higher than the score of 50 on the Zung scale in fatigued survivors compared to non-fatigued survivors (p = 0.0006). Conclusions: Our results suggest that an altered balance of chemokines, cytokines and growth factors serum levels may be associated to presence of symptoms such as fatigue and pain in breast cancer survivors at an average of 5 years after diagnosis

A roadmap towards breast cancer therapies supported by explainable artificial intelligence

In recent years personalized medicine reached an increasing importance, especially in the design of oncological therapies. In particular, the development of patients’ profiling strategies suggests the possibility of promising rewards. In this work, we present an explainable artificial intelligence (XAI) framework based on an adaptive dimensional reduction which (i) outlines the most important clinical features for oncological patients’ profiling and (ii), based on these features, determines the profile, i.e., the cluster a patient belongs to. For these purposes, we collected a cohort of 267 breast cancer patients. The adopted dimensional reduction method determines the relevant subspace where distances among patients are used by a hierarchical clustering procedure to identify the corresponding optimal categories. Our results demonstrate how the molecular subtype is the most important feature for clustering. Then, we assessed the robustness of current therapies and guidelines; our findings show a striking correspondence between available patients’ profiles determined in an unsupervised way and either molecular subtypes or therapies chosen according to guidelines, which guarantees the interpretability characterizing explainable approaches to machine learning techniques. Accordingly, our work suggests the possibility to design data-driven therapies to emphasize the differences observed among the patients