Effect of Mass Supplementation with Ready-to-Use Supplementary Food during an anticipated nutritional emergency

Previous studies have shown the benefits of ready-to-use supplementary food (RUSF) distribution in reducing the incidence and prevalence of severe acute malnutrition

Molecular apocrine tumours in EORTC 10994/BIG 1-00 phase III study: pathological response after neoadjuvant chemotherapy and clinical outcomes

Background: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers. Methods: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and “other”. The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes. Results: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4–43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2–68.6). Patients with MA and TN basal-like tumours have lower survival outcomes. Conclusions: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prognostic Value of Routinely Measured Inflammatory Biomarkers in Older Cancer Patients: Pooled Analysis of Three Cohorts

BACKGROUND: The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routine inflammatory biomarkers. METHODS: A pooled analysis of prospective multicenter cohorts of cancer patients aged >/=70 was performed. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP /= 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). One-year mortality was assessed using Cox models. Discriminative power was assessed using Harrell's C index (C) and net reclassification improvement (NRI). RESULTS: Overall, 1800 patients were analyzed (mean age: 79 +/- 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality in patients not at risk of frailty (hazard ratio [95% confidence interval] = 4.48 [2.03-9.89] for GPS1, 11.64 [4.54-29.81] for GPS2, and 7.15 [3.22-15.90] for CRP/albumin ratio > 0.215) and in patients at risk of frailty (2.45 [1.79-3.34] for GPS1, 3.97 [2.93-5.37] for GPS2, and 2.81 [2.17-3.65] for CRP/albumin ratio > 0.215). The discriminative power of the baseline clinical model (C = 0.82 [0.80-0.83]) was increased by adding GPS (C = 0.84 [0.82-0.85]; NRI events (NRI+) = 10% [2-16]) and CRP/albumin ratio (C = 0.83 [0.82-0.85]; NRI+ = 14% [2-17]). CONCLUSIONS: Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients

Insight into sensitivity mechanisms to antiandrogens in molecular apocrine breast carcinoma

Les cancers moléculaires apocrines sont un sous-groupe de cancer du sein caractérisé par l'expression du récepteur aux androgènes (RA), l'absence du récepteur aux oestrogènes (RE) et l'expression paradoxale de nombreux gènes typiquement exprimés dans les tumeurs RE positives. Une proportion significative de ces patientes va récidiver sous forme de métastases dont la prise en charge repose sur des traitements non spécifiques (chimiothérapies). En préclinique, la lignée cellulaire MDA-MB-453 a été identifiée comme ayant un profil transcriptomique similaire à ce sous-groupe tumoral. En clinique, les essais réalisés dans ce sousgroupe tumoral avec différents anti-androgènes, dont l’abiratérone (inhibiteur de la synthèse des androgènes), retrouvent un bénéfice clinique chez environ 25% des patientes. L’objectif de cette thèse est d’améliorer les connaissances et les prises en charge thérapeutiques spécifiques de ces tumeurs. Nos données précliniques comparatives montrent que l'ODM-201, nouvel antiandrogène, ne présente pas une efficacité supérieure par rapport aux antiandrogènes déjà étudiés. Afin de contourner les limites des lignées cellulaires identifiées dans ce premier projet, nous avons démontré la nécessité de développer de nouveaux modèles : les Patient-Derived-Xenograft orthotopiques. Notre deuxième projet est en faveur d’une meilleure sélection des patientes à traiter par abiratérone notamment basé sur des caractéristiques immunohistochimiques apocrines. Chez les patientes ne présentant pas ces caractéristiques, nous avons isolé CHEK1 comme une cible d’intérêt en combinaison thérapeutique pour majorer les taux de réponse de l’abiratérone en monothérapie.Molecular apocrine cancers are a subgroup of breast cancer characterized by the expression of the androgen receptor (AR), the absence of the estrogen receptor (ER) and the paradoxical expression of many genes typically expressed in ER positive tumors. A significant proportion of these patients will recur in the form of metastases whose management is based on non-specific treatments (chemotherapy). In preclinical study, the MDA-MB-453 cell line was identified as having a transcriptomic profile similar to this tumor subgroup. Clinical trials in this tumor subgroup testing different antiandrogens, including abiraterone (inhibitor of androgen synthesis), found a clinical benefit in about 25% of patients. The aim of this thesis is to improve the knowledge and the specific therapeutic management of these tumors. Our comparative preclinical data show that ODM-201, a new anti-androgen, does not show superior efficacy compared to previously studied anti-androgens. In order to circumvent the limits of cell lines provided by this first project, we have shown the need to develop new models: orthotopic Patient-Derived-Xenograft. Our second project favors a better selection of patients to be treated with abiraterone, especially based on apocrine immunohistochemical characteristics. In patients without these characteristics, we isolated CHEK1 as a target of interest in combination therapy to increase response rates of abiraterone monotherapy

Contribution à l’étude des mécanismes de sensibilité aux traitements antiandrogènes dans les cancers du sein moléculaires apocrines

Molecular apocrine cancers are a subgroup of breast cancer characterized by the expression of the androgen receptor (AR), the absence of the estrogen receptor (ER) and the paradoxical expression of many genes typically expressed in ER positive tumors. A significant proportion of these patients will recur in the form of metastases whose management is based on non-specific treatments (chemotherapy). In preclinical study, the MDA-MB-453 cell line was identified as having a transcriptomic profile similar to this tumor subgroup. Clinical trials in this tumor subgroup testing different antiandrogens, including abiraterone (inhibitor of androgen synthesis), found a clinical benefit in about 25% of patients. The aim of this thesis is to improve the knowledge and the specific therapeutic management of these tumors. Our comparative preclinical data show that ODM-201, a new anti-androgen, does not show superior efficacy compared to previously studied anti-androgens. In order to circumvent the limits of cell lines provided by this first project, we have shown the need to develop new models: orthotopic Patient-Derived-Xenograft. Our second project favors a better selection of patients to be treated with abiraterone, especially based on apocrine immunohistochemical characteristics. In patients without these characteristics, we isolated CHEK1 as a target of interest in combination therapy to increase response rates of abiraterone monotherapy.Les cancers moléculaires apocrines sont un sous-groupe de cancer du sein caractérisé par l'expression du récepteur aux androgènes (RA), l'absence du récepteur aux oestrogènes (RE) et l'expression paradoxale de nombreux gènes typiquement exprimés dans les tumeurs RE positives. Une proportion significative de ces patientes va récidiver sous forme de métastases dont la prise en charge repose sur des traitements non spécifiques (chimiothérapies). En préclinique, la lignée cellulaire MDA-MB-453 a été identifiée comme ayant un profil transcriptomique similaire à ce sous-groupe tumoral. En clinique, les essais réalisés dans ce sousgroupe tumoral avec différents anti-androgènes, dont l’abiratérone (inhibiteur de la synthèse des androgènes), retrouvent un bénéfice clinique chez environ 25% des patientes. L’objectif de cette thèse est d’améliorer les connaissances et les prises en charge thérapeutiques spécifiques de ces tumeurs. Nos données précliniques comparatives montrent que l'ODM-201, nouvel antiandrogène, ne présente pas une efficacité supérieure par rapport aux antiandrogènes déjà étudiés. Afin de contourner les limites des lignées cellulaires identifiées dans ce premier projet, nous avons démontré la nécessité de développer de nouveaux modèles : les Patient-Derived-Xenograft orthotopiques. Notre deuxième projet est en faveur d’une meilleure sélection des patientes à traiter par abiratérone notamment basé sur des caractéristiques immunohistochimiques apocrines. Chez les patientes ne présentant pas ces caractéristiques, nous avons isolé CHEK1 comme une cible d’intérêt en combinaison thérapeutique pour majorer les taux de réponse de l’abiratérone en monothérapie

Qualité de publication des essais de phase II en oncologie

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Efficacy of antiandrogens in androgen receptor-positive triple-negative metastatic breast cancer: Real-life data

Antiandrogens (AA) have been tested in clinical trials in androgen receptor (AR) + triple-negative breast cancer (TNBC). We aim to assess the clinical benefit rate (CBR) of AA in real life.The primary end-point was CBR at 6 months. Twenty-four patients were assessable and received: abiraterone acetate (62 %), enzalutamide (8 %) and bicalutamide (30 %). CBR at 6 months was 29 % (7/24) with 2 CR, 3 PR and 2 SD. Four patients had a clinical benefit >12 months. Real-life efficacy of AA use in metastatic AR + TNBC are in line with data from published trials