Lymphopenia combined with low TCR diversity (divpenia) predicts poor overall survival in metastatic breast cancer patients

Lymphopenia (< 1Giga/L) detected before initiation of chemotherapy is a predictive factor for death in metastatic solid tumors. Combinatorial T cell repertoire (TCR) diversity was investigated and tested either alone or in combination with lymphopenia as a prognostic factor at diagnosis for overall survival (OS) in metastatic breast cancer (MBC) patients. The combinatorial TCR diversity was measured by semi quantitative multi-N-plex PCR on blood samples before the initiation of the first line chemotherapy in a development (n = 66) and validation (n = 67) MBC patient cohorts. A prognostic score, combining lymphocyte count and TCR diversity was evaluated. Univariate and multivariate analyses of prognostic factors for OS were performed in both cohorts. Lymphopenia and severe restriction of TCR diversity called “divpenia” (diversity ≤ 33%) were independently associated with shorter OS. Lympho-divpenia combining lymphopenia and severe divpenia accurately identified patients with poor OS in both cohorts (7.6 and 10.6 vs 24.5 and 22.9 mo). In multivariate analysis including other prognostic clinical factors, lympho-divpenia was found to be an independent prognostic factor in the pooled cohort (p = 0.005) along with lack of HER2 and hormonal receptors expression (p = 0.011) and anemia (p = 0.009). Lympho-divpenia is a novel prognostic factor that will be used to improve quality of MBC patients’ medical care

A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers

HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism

Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

IntroductionObesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification.MethodsWe performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003–02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype.ResultsMultivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype.ConclusionsSeverely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes

Online citizen joumalism : a reified public? : Public Talks: Communicating in the City

Le « journalisme citoyen » en ligne est issu des phénomènes d'autopublication sur Internet. Il propose une nouvelle représentation du public comme acteur social capable d'assurer les couverures médiatiques aux côtés du journaliste. Toutefois, la production de nouveaux discours ne se fait pas sans contradictions, qui interrogent l'évolution du journalisme à ses marges. À partir des expérimentations de Place publique et d'AgoraVox, l'article examine l'instrumentalisation de la figure du public dans une reconfiguration de l'espace journalistique

Les blogs de BD comme « monde social » amateur

National audienc

Les mondes du blog (contribution à l'analyse du phénomène des blogs en France)

Les blogs ont marqué les années 2000, passant de quelques centaines d espaces créés au début de la décennie à quelques 160 millions d unités indexées par les moteurs de recherche dédiés. Ce travail doctoral entend contribuer à la compréhension du phénomène et de sa dynamique. Il est principalement centré sur le cas français sur une période courant de 2002, lorsque les premières plateformes de blogs apparaissent, jusqu à 2009, quand entrent en lice des sites qualifiés de réseaux sociaux. Deux démarches empiriques ont été menées de front. La première a reposé sur l observation générale des dynamiques qui ont accompagné l essor des blogs. Ce travail montre que les mondes du blog sont marqués par un processus de segmentation. Celle-ci est liée à des formes d appropriation différenciées d un même format de publication, donnant naissance à une variété de mondes sociaux entrecroisés. La seconde démarche a reposé sur le suivi longitudinal des carrières de dix blogueurs sur la période. Pour ces derniers, les mondes du blog ont offert un cadre à des activités de publication. Ils ont progressivement appris à évoluer dans une semi-obscurité dans le but de ne pas jouir d une trop grande visibilité, tout en trouvant les ressources nécessaires à l entretien de leurs sociabilités culturelles. À l articulation de ces deux approches de terrain se déploie la notion interactionniste de monde social, combinée avec des sociologies de la médiation, des attachements et du goût. Derrière cet assemblage méthodologique, c est finalement un autre objet qui transparaît : la réception. Ce travail est aussi une tentative pour comprendre les publics des blogsThe 2000s have been marked by blogs, starting out with the creation of a few hundred blogs spaces at the start of the decade to number around 160 million units indexed by dedicated search engines. This doctoral thesis aims to contribute to undestanding the phenomenon and its dynamics. France is the main focus of study, from 2002 when the first blog platforms began to appear, until 2009 when the websites qualifying as social networks entered the arena. Two empirical approaches have been adopted. The first approach consists of a general observation of the dynamics which surrounded the soar in the development of blogs. We demonstrate that the world of blogs can be identified by a process of segmentation, linked to differentiated forms of appropriation of the same publication format, giving rise to a variety of intertwined social worlds. The second approach comprises a longitudinal study of the "careers" of ten bloggers over the reference period. For these individuals, the world of blogs has enabled them to undertake publication activities. Over time, they have learned how to progress in the blog world twilight zone, thereby avoiding excessive visibility whilst still finding the resources necessary to remaining culturally sociable. At the crossroads these approaches in the field, lies the interactionist notion of the social world, combined with the sociologies of mediation, attachment and taste. Behind this methodological assembly, another object becomes apparent : the reception. This work also seeks to understand the blog publicRENNES1-BU Droit éco. gestion (352382104) / SudocSudocFranceF

Les premiers pas de l’informatique dans les rédactions : l’exemple de journalistes amateurs d’informatique au début des années 1980

International audienc

Evolution et prise de poids après le diagnostic de cancer du sein (suivi d'une étude prospective française)

LYON1-BU Santé (693882101) / SudocSudocFranceF

PI3K targeting in breast cancer: the end of the beginning?

International audienc