High-Resolution Comparative Genomic Hybridization of Inflammatory Breast Cancer and Identification of Candidate Genes

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples. METHODOLOGY/FINDINGS: Genomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent "complex" patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs. The percentage of genes whose mRNA expression correlated with CNAs was similar in both types for the gained genes, but ∼7-fold lower in IBCs for the lost genes. Integrated analysis identified 24 potential candidate IBC-specific genes. Their combined expression accurately distinguished IBCs and nIBCS in an independent validation set, and retained an independent prognostic value in a series of 1,781 nIBCs, reinforcing the hypothesis for a link with IBC aggressiveness. Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration. CONCLUSIONS: Our results suggest a higher genomic instability of IBC. We established the first repertory of DNA copy number alterations in this tumor, and provided a list of genes that may contribute to its aggressiveness and represent novel therapeutic targets

Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer

International audienceIntroduction: Breast cancers are traditionally divided into hormone-receptor positive and negative cases. This classification helps to guide patient management. However, a subgroup of hormone-receptor positive patients relapse irrespective of hormonal therapy. Gene expression profiling has classified breast tumours into five major subtypes with significant different outcome. The two luminal subtypes, A and B, show high expression of ESR1, GATA3 and FOXA1 genes. Prognostic biomarkers for oestrogen receptor (ER)-positive cases include progesterone receptor (PR) and androgen receptor (AR), and proteins related to proliferation or apoptotic resistance. The aim of this study was to identify the best predictors of success of hormonal therapy.Methods: By immunohistochemistry we studied 10 markers in a consecutive series of 832 cases of breast carcinoma treated at the Paoli-Calmettes Institute from 1990 to 2002 and deposited onto tissue microarrays (TMA). These markers were luminal-related markers ER, PR, AR, FOXA1 and GATA3 transcription factors, proliferation-related Ki67 and CCND1, ERBB2, anti-apoptotic BCL2 and P53. We also measured vascular peritumoural invasion (VPI), size, grade and lymph node involvement. For 143 cases, gene expression profiles were available. Adjuvant chemotherapy and hormonal therapy were given to high- and low-risk patients, respectively. The 162 events observed and taken into account were metastases.Results: Molecular expression of the 10 parameters and subtype with ER status were strongly correlated. Of the 67 luminal A cases of this series, 63 were ER-positive. Multivariate analyses showed the highly significant prognostic value of VPI (hazard ratio (HR) = 2.47), Ki67 (HR = 2.9), P53 (HR = 2.9) and GATA3 (HR = 0.5) for the 240 patients who received hormonal therapy.Conclusions: A panel of three antibodies (Ki67, P53 and GATA3) associated with VPI can significantly improve the traditional prognosticators in predicting outcome for ER-positive breast cancer patients receiving hormonal therapy

External Validation of the SERC Trial Population: Comparison with the Multicenter French Cohort, the Swedish and SENOMIC Trial Populations for Breast Cancer Patients with Sentinel Node Micro-Metastasis

Many trials confirmed the safety of omitting axillary dissection in the selected patients treated for early breast cancer. The external validity of these trials is questionable. Our study aimed to evaluate the accuracy of the French population representativity in the SERC trial and the differences between these two populations as well as comparing the French and the Swedish populations (the SENOMIC trial population and the Swedish National Breast Cancer Registry (NKBC) cohort) of patients with sentinel node (SN) micro-metastasis. A higher rate of smaller tumors and grade 1 tumors was observed in the French cohort when compared to the SERC population. Our findings conclude that both French populations show similar characteristics. Positive non-sentinel node (NSN) rates at completion axillary lymph node dissection (ALND) were 10.28 % and 11.3 % in the SERC trial and French cohort, respectively (p = 0.5). The rate of grade 1 tumors was lower in the SENOMIC trial (16.2%) and in the NKBC cohort (17.4%) compared to the SERC trial population (27.3%) and the French cohort (34.4%). Our findings in addition to the previously demonstrated concordance between the SENOMIC trial and the NKBC populations imply that the results of both the SERC and the SENOMIC trials can be applied to both French and Swedish real populations

Reconstruction after anterior pelvic exenteration

Anterior pelvic exenterations for gynecologic cancer are usually performed for local or loco-regional recurrences and advanced local tumors, in most cases after radiotherapy and brachytherapy. The aim of pelvic reconstructions achieved during the same time are preservations of urinary, digestive and, when possible, sexual functions, with a decrease of post-operative complication rate and preservation of quality of life. The different techniques of urinary diversion, vaginal reconstruction and pelvic filling are discussed with analyze of specific morbidity and practice evolution

Reconstruction after anterior pelvic exenteration

Anterior pelvic exenterations for gynecologic cancer are usually performed for local or loco-regional recurrences and advanced local tumors, in most cases after radiotherapy and brachytherapy. The aim of pelvic reconstructions achieved during the same time are preservations of urinary, digestive and, when possible, sexual functions, with a decrease of post-operative complication rate and preservation of quality of life. The different techniques of urinary diversion, vaginal reconstruction and pelvic filling are discussed with analyze of specific morbidity and practice evolution

Facteurs pronostiques et implications thérapeutiques dans le cancer du sein de petite taille T1a-T1b (mise au point)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

un Score simple prédictif de la récidive locale après traitement concervateur du cancer du sein

BUT: définir les facteurs prédictifs indépendants de la récidive locale (RL) après traitement conservateur du cancer du sein et établir un score prédictif de RL. METHODES: 4635 patientes ayant bénéficié d'un traitement conservateur pour cancer du sein infiltrant de 1980 à 2005 ont été incluses. Les données étudiées ont été: l'âge, la date de la chirurgie et de RL, les traitements adjuvants et les données histologiques (taille, statut des berges d'exérèse, récepteurs hormonaux (RH), emboles vasculaires péritumoraux (EVPT), grade SBR et statut ganglionnaire). RESULTATS: Le taux de RL est de 5,7%, 8,4% et 11,1% à 5,7 et 10 ans. L'analyse univariée réalisée par le test de Gray retrouve 5 facteurs de risque significatifs de RL: grade SBR III (HR 1,48; IC95 [1,16-1,88], p<0,0013), présence d'EVPT (HR 1,31; IC95 [1,03-1,65], p<0,03), âge <= 40 ans (HR 0,47; IC 95 [0,36-0,61], p<0,0001), RH négatifs (HR 0,41 IC95 [0,32-0,52], p<0,0001) et berges d'exérèse chirurgicale atteintes (HR 2,29; IC95 [1,75-2,99], p<0,0001). Une analyse multivariée selon le modèle de Fine & Gray retrouve les trois derniers comme facteurs significativement indépendants. Du fait d'un valeur statistique équivalente de chacun de ces facteurs, un score pronostic de la RL définissant 4 groupes en fonction du nombre de facteurs présents (0,1 ou plus) a été proposé. Les taux de RL et de survie sans récidive (calculées par l'estimateur de Prentice) étaient significativement différents dans les 4 groupes. CONCLUSION: Le groupe score = 0, dont l'effectif est majoritaire, apparaît commet était à bas risque et pourrait définir un groupe éligible à une irradiation partielle exclusive par radiothérapie per-opératoireAIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Un second traitement conservateur après récidive locale de cancer du sein (une alternative à la mastectomie ?)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF