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Jacot W.,CRLC Val dAurelle Paul Lamarque | Lopez-Crapez E.,Laboratoire Of Biologie Specialisee Et Doncogenetique | Thezenas S.,CRLC Val dAurelle Paul Lamarque | Senal R.,Laboratoire Of Biologie Specialisee Et Doncogenetique | And 4 more authors.
Breast Cancer Research | Year: 2011

Introduction: Triple-negative breast cancers (TNBCs) are characterised by lack of expression of hormone receptors and epidermal growth factor receptor 2 (HER-2). As they frequently express epidermal growth factor receptors (EGFRs), anti-EGFR therapies are currently assessed for this breast cancer subtype as an alternative to treatments that target HER-2 or hormone receptors. Recently, EGFR-activating mutations have been reported in TNBC specimens in an East Asian population. Because variations in the frequency of EGFR-activating mutations in East Asians and other patients with lung cancer have been described, we evaluated the EGFR mutational profile in tumour samples from European patients with TNBC.Methods: We selected from a DNA tumour bank 229 DNA samples isolated from frozen, histologically proven and macrodissected invasive TNBC specimens from European patients. PCR and high-resolution melting (HRM) analyses were used to detect mutations in exons 19 and 21 of EGFR. The results were then confirmed by bidirectional sequencing of all samples.Results: HRM analysis allowed the detection of three EGFR exon 21 mutations, but no exon 19 mutations. There was 100% concordance between the HRM and sequencing results. The three patients with EGFR exon 21 abnormal HRM profiles harboured the rare R836R SNP, but no EGFR-activating mutation was identified.Conclusions: This study highlights variations in the prevalence of EGFR mutations in TNBC. These variations have crucial implications for the design of clinical trials involving anti-EGFR treatments in TNBC and for identifying the potential target population. © 2012 Jacot et al.; licensee BioMed Central Ltd.

Lamy P.-J.,Unite de Recherche Clinique | Lamy P.-J.,Institute Medical dAnalyse Genomique | Gauchez A.-S.,Grenoble University Hospital Center | Gauchez A.-S.,Societe Francaise de Medecine Nucleaire | And 16 more authors.
Annales de Biologie Clinique | Year: 2016

To systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review. We attributed a level of evidence (LoE) of IA to PSA for early PCA detection, but we do not recommend its use in mass screening. Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5); fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCA mortality. The LoE attributed was III-C. PSA can be used for early prostate cancer detection but mass screening is not recommended. Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed. A better use of available tests is possible for men at risk in order to maximize the risk-benefit ratio. Copyright © 2016 JLE.

Lamy P.-J.,Center Regional Of Lutte Contre Le Cancer Val Daurelle Paul Lamarque | Fina F.,Laboratoire Of Transfert Doncologie Biologie | Bascoul-Mollevi C.,Unite Of Biostatistique Center Regional Of Lutte Contre Le Cancer Val Daurelle | Laberenne A.-C.,Center Regional Of Lutte Contre Le Cancer Val Daurelle Paul Lamarque | And 3 more authors.
Breast Cancer Research | Year: 2011

Introduction: Human epidermal growth factor receptor 2 (HER2)-amplified breast cancers represent a tumor subtype with chromosome 17q rearrangements that lead to frequent gene amplifications. The aim of this study was to quantify the amplification of genes located on chromosome 17q and to analyze the relations between the pattern of gene amplifications and the patients' characteristics and survival.Methods: Patients with HER2-positive breast tumors (HER2 score of 3+ by immunohistochemistry or positive for HER2 amplification by fluorescence in situ hybridization (FISH)) (n = 86) and with HER2-negative breast tumors (n = 40) (negative controls) were included in this study. Using a quantitative polymerase chain reaction method and DNA extracted from frozen tumor specimens, 11 genes (MED1, STARD3, HER2, GRB7, THRA, RARA, TOP2A, IGFBP4, CCR7, KRT20, KRT19 and GAS), which are localized within Chr17q12-q21 and have a putative role in breast cancer development, were quantified. Relapse-free and overall survival rates were estimated from the date of surgery to the date of the event of interest (recurrence or death) using the Kaplan-Meier method.Results: Gene amplification was observed only in HER2-positive tumors, and the frequency of amplification decreased with the distance of the gene from HER2. HER2 presented the highest level of amplification. TOP2A was not included in the smallest region of amplification involving HER2. Amplification of RARA, KRT20 and KRT19 was significantly associated with node-positive breast cancer (P = 0.030, P = 0.002 and P = 0.033, respectively). During a median follow-up period of 55 months (range, 6 to 81 months), the subgroup of patients with hormone receptor-negative cancer and without TOP2A amplification showed the worst survival (relapse-free survival: hazard ratio (HR) = 0.29, 95% confidence interval (95% CI), 0.13 to 0.65, P = 0.001; and overall survival: HR = 0.28, 95% CI, 0.10 to 0.76, P = 0.008).Conclusions: HER2 amplification seems to drive genomic instability along chromosome 17q, leading to different patterns of gene amplification. This study confirms the clinical importance of identifying, among patients with HER2-positive breast tumors, the subgroup of patients with hormone receptor-negative and nonamplified TOP2A cancers as they have the worst prognosis. © 2011 Lamy et al.; licensee BioMed Central Ltd.

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