A prospective comparison of ER, PR, Ki67 and gene expression in paired sequential core biopsies of primary, untreated breast cancer

BACKGROUND: Sequential biopsy of breast cancer is used to assess biomarker effects and drug efficacy. The preoperative "window of opportunity" setting is advantageous to test biomarker changes in response to therapeutic agents in previously untreated primary cancers. This study tested the consistency over time of paired, sequential biomarker measurements on primary, operable breast cancer in the absence of drug therapy. METHODS: Immunohistochemistry was performed for ER, PR and Ki67 on paired preoperative/operative tumor samples taken from untreated patients within 2 weeks of each other. Microarray analysis on mRNA extracted from formalin fixed paraffin embedded cores was performed using Affymetrix based arrays on paired core biopsies analysed using Ingenuity Pathway Analysis (IPA) and Gene Set Analysis (GSA). RESULTS: In 41 core/resection pairs, the recognised trend to lower ER, PR and Ki67 score on resected material was confirmed. Concordance for ER, PR and Ki67 without changing biomarker status (e.g. ER+ to ER-) was 90, 74 and 80 % respectively. However, in 23 paired core samples (diagnostic core v on table core), Ki67 using a cut off of 13.25 % was concordant in 22/23 (96 %) and differences in ER and PR immunohistochemistry by Allred or Quickscore between the pairs did not impact hormone receptor status. IPA and GSA demonstrated substantial gene expression changes between paired cores at the mRNA level, including reduced expression of ER pathway analysis on the second core, despite the absence of drug intervention. CONCLUSIONS: Sequential core biopsies of primary breast cancer (but not core versus resection) was consistent and is appropriate to assess the effects of drug therapy in vivo on ER, PR and Ki67 using immunohistochemistry. Conversely, studies utilising mRNA expression may require non-treatment controls to distinguish therapeutic from biopsy differences

Corticosteroid treatment before TAVI and the risk of pacemaker implantation: A 2:1 matching study

International audienc

Long-term follow-up of silent and symptomatic atrial fibrillations during acute myocardial infarction : not an epiphenomenon

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Relathionship between high risk scintigraphic score and elevated REACH score in 6 months after a first acute coronary syndrome

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The Free Oxygen Radicals Test (FORT) to assess circulating oxidative stress in patients with acute myocardial infarction

International audienceBackground and aim: Reactive oxygen species (ROS) play an important role in the pathogenesis of many diseases including cardiovascular diseases. Several methods have been developed for the direct or indirect measurement of oxygen free radical and its by-products. The current study was designed to validate the new Free Oxygen Radicals Test (FORT) and to investigate the potential relationships between ROS and clinical or biological factors in male patients with acute myocardial infarction (AMI). Methods: We analysed FORT values in samples from 66 patients with AMI. Results: FORT values ranged from 324 to 1198 FORT units, with a median value of 581 (494-754) FORT units. In univariate analysis, FORT values were positively related only to LVEF <40% (p=0.005), levels of CRP (r=0.438, p<0.001) and peak CK (r=0.274, p=0.028). Multiple linear regression analysis showed that CRP (p=0.023), LVEF <40% (p<0.001) and the presence of diabetes (p=0.039) were independent predictors of serum FORT values. This statistical model can explain 45% of the variance in FORT values (R 2 =0.45). Conclusions: The FORT is a simple tool to assess circulating ROS in routine clinical practice. Oxidative conditions such as inflammation and diabetes are the major determinants of FORT values in patients with AMI

Mean systolic blood pressure after admission for myocardial infarction is associated with one year mortality among elderly patients

IF 6.968International audienc

Stress at work burden as new risk factor in patients with acute cerebro- or cardiovascular events: Preliminary findings from INEV@L, a prospective pilot study

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