[The link between aggressive behavior and depression in adolescence. A cross-sectional study conducted in the psychiatric emergency unit at the Sainte-Anne hospital]. / Lien entre comportements agressifs et vécu dépressif chez l'adolescent. Une étude transversale menée au centre psychiatrique d'orientation et d'accueil de l'hôpital Sainte-Anne.

INTRODUCTION: The link between depression and aggressive behavior in adults has been found in many studies. In adolescents, this relationship is still controversial. Several studies point out that irritability is a key symptom in adolescent depressed. Few studies have analyzed precisely the kind of aggressive behavior. This study sets out to assess the relationship between aggressive behavior and depressive affects in adolescents. We also pay attention in this population to hopelessness feelings, anxiety, global functioning and the type of aggressive behavior. METHOD: This is a descriptive and observational cross-sectional study. Data was collected from 49 successive adolescents admitted for a 24-hour evaluation in the emergency department of the Sainte-Anne psychiatric hospital. The inclusion period was from February to April 2012, with age limits between 15 and 18. For each patient, the clinician completed with the parents or other caregivers the Modified Overt Aggressive Scale (MOAS) searching for existence of aggressive behavior in the week prior to the consultation. The population was divided into two groups: P- group when the MOAS score was < 3 and the P+ group when the MOAS score was ≥ 3. The Global Assessment of Functioning Scale and Adolescent Depression Rating Scale for clinicians (ADRSc) were also completed. Each patient completed the self-report Buss-Perry Aggression Questionnaire (QA), the Beck Hopelessness scale and the Adolescent Depression Rating Scale for patients (ADRSp). RESULTS: Forty-nine adolescents with a median age of 16 years and 4 months participated. The first reason for consultation was depressive symptoms, followed by disruptive behavior. The analysis was conducted on 39 questionnaires. The demographic profile of the two groups was similar. We did not find any significant difference between the groups P+ and P- on ADRSc scores and secondary criteria. However, we found higher scores in the QA in the more depressed patient, especially a higher hostility score in this sample. In the subgroup analysis: as expected self-aggressive behavior was associated with a higher depression score, more hospitalization and a poor global functioning score. Surprisingly, the patients who showed physical aggression against others had a better prognosis and lower depression scores. DISCUSSION: The study did not conclude on the link between aggressive behavior and depression in this population. The adolescent hostility appears more characteristic of depression compared to other dimensions of aggressivity (anger, verbal aggression, physical aggression) in adolescents. Physical aggression against others appeared not only less typical in depression but was also associated with a better global functioning. Clinicians should pay particular attention to the kind of aggressive behavior in clinical evaluations of adolescents in an emergency context.

[Decision of emergency involuntary hospitalization: categorical or dimensional approach?]. / La décision d'hospitalisation sans consentement aux urgences: approche dimensionnelle ou catégorielle?

BACKGROUND: In 2005, in its recommendations on the modalities of decision making for compulsory hospitalization, the French Health High Authority (HAS) had already stressed the need for rapid implementation of studies and epidemiological analyses on the subject to compensate the lack of adequate data in France. The new French law of July 5, 2011, on the rights and protection of persons under psychiatric care, establishes a judicial review of decisions for compulsory hospitalization. Therefore, healthcare professionals need to better define and characterize the criteria for such decisions, especially in their relation to psychopathology. The concept of capacity to consent to treatment includes the ability to understand (to receive information about the disease), the ability to appreciate (to weigh the risks and benefits of treatment), the ability to reason (determining the best choice rationally) and the ability to freely express a decision. However, assessment tools of capacity to consent to treatment seem to fail to predict the modality of hospitalization. OBJECTIVE: This study examined the impact of clinical and contextual characteristics on the decision in emergency services to admit patients to compulsory inpatient psychiatric units. METHOD: Data was collected from 442 successive patients admitted to hospital for care from five psychiatric emergency facilities in Paris and covered sociodemographic information, previous hospitalizations, recent course of care, clinical diagnosis, Global Assessment of Functioning scale (GAF) and Insight measured by the Q8 Bourgeois questionnaire. Patients were also assessed based on criteria established by the HAS for the severity of mental disorders and the necessity of emergency care. RESULTS: Multivariable logistic regression shows that diagnosis does not affect the decision of hospitalization. Agitation, aggressiveness toward others, being married as well as being referred by a doctor or family are all factors that increase the risk of involuntary hospitalization. Last, low Q8 and GAF scores are strong predictors for compulsory admission. CONCLUSION: Our study shows a dimensional rather than categorical assessment of patients by clinicians. Assessment of insight is the main operational criterion used by clinicians in our study. This supports using insight and GAF evaluation in clinical practice to clarify assessment and decision-making in an emergency setting regarding compulsory hospitalization.

Association of the CD226 Ser(307) variant with systemic sclerosis: evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis.

OBJECTIVE: The nonsynonymous polymorphism rs763361 of the CD226 gene, which encodes DNAX accessory molecule 1, which is involved in T cell costimulation pathways, has recently been identified as a genetic risk factor for autoimmunity. The purpose of this study was to test for association of the CD226 rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations. METHODS: CD226 rs763361 was genotyped in 3,632 individuals, consisting of a discovery sample (991 SSc patients and 1,008 controls) and a replication sample (999 SSc patients and 634 controls). All study subjects were of European Caucasian origin. Expression of CD226 was assessed on peripheral blood mononuclear cells obtained from 21 healthy donors genotyped for CD226 rs763361. RESULTS: The CD226 rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] 1.10-1.34), P = 5.69 × 10(-5) . The CD226 T allele was also associated with various SSc subsets, highlighting a potential contribution to disease severity. The most remarkable associations of the CD226 TT risk genotype were observed with the diffuse cutaneous SSc subtype, the anti-topoisomerase I antibody-positive, and SSc-related fibrosing alveolitis subsets: OR 1.86 (95% CI 1.42-2.43), P = 5.15 × 10(-6) , OR 1.82 (95% CI 1.38-2.40), P = 2.16 × 10(-5) , and OR 1.61 (95% CI 1.25-2.08), P = 2.73 × 10(-4) , respectively. CD226 expression was not significantly influenced by CD226 rs763361 genotypes whatever the T cell subtype investigated. CONCLUSION: Our results establish CD226 as a new SSc genetic susceptibility factor underlying the contribution of costimulation pathways in the pathogenesis of SSc. Further work is nevertheless needed to define the causal variant at the CD226 locus as well as the functional consequences.

Evidence of the contribution of the X chromosome to systemic sclerosis susceptibility: association with the functional IRAK1 196Phe/532Ser haplotype.

OBJECTIVE: Several autoimmune disorders, including systemic sclerosis (SSc), are characterized by a strong sex bias. To date, it is not known whether genes on the sex chromosomes influence SSc susceptibility. Recently, an IRAK1 haplotype that contains the 196Phe functional variant (rs1059702), located on Xq28, was found to confer susceptibility to systemic lupus erythematosus (SLE). This study was undertaken to test for an association between SSc and the IRAK1 SLE risk haplotype. METHODS: We tested for an association with the IRAK1 SLE risk haplotype in a discovery set of 849 SSc patients and 625 controls. IRAK1 rs1059702 was further genotyped in a replication set, which included Caucasian women from Italy (493 SSc patients and 509 controls) and Germany (466 SSc patients and 1,083 controls). RESULTS: An association between the IRAK1 haplotype and SSc was detected in the discovery set. In both the discovery and replication sets, the rs1059702 TT genotype was found to be associated with specific SSc subsets, highlighting a potential contribution to disease severity. A meta-analysis provided evidence of an association of both the T allele and TT genotype with the overall disease, with an odds ratio (OR) of 1.20 and 95% confidence interval (95% CI) of 1.06-1.35 for the T allele (P = 0.003) and an OR of 1.49 and 95% CI of 1.06-2.10 for the TT genotype (P = 0.023). However, the most notable associations were observed with the diffuse cutaneous, anti-topoisomerase I antibody positive, and SSc-related fibrosing alveolitis subsets (OR 2.35 [95% CI 1.51-3.66], P = 1.56 × 10(-4), OR 2.84 [95% CI 1.87-4.32], P = 1.07 × 10(-6), and OR 2.09 [95% CI 1.35-3.24], P = 9.05 × 10(-4), respectively). CONCLUSION: Our study provides the first evidence of an association between IRAK1 and SSc, demonstrating that a sex chromosome gene directly influences SSc susceptibility and its phenotypic heterogeneity.

NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis.

BACKGROUND: Recent evidence has highlighted a potential role of interleukin 1ß (IL-1ß) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1ß. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders. OBJECTIVE: /st> To study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population. METHODS: NLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin. RESULTS: Conditional analyses revealed a significant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fibrosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA. CONCLUSIONS: Our results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease.

Association of a KCNA5 gene polymorphism with systemic sclerosis-associated pulmonary arterial hypertension in the European Caucasian population.

OBJECTIVE: Pulmonary arterial hypertension (PAH) has emerged as a leading cause of death in systemic sclerosis (SSc). The genetic basis of PAH has been unraveled in recent years, with a major role played by transforming growth factor ß receptors; however, some other candidate genes have also been advocated, including potassium voltage-gated channel, shaker-related subfamily, member 5 (KCNA5). We undertook this study to determine whether KCNA5 polymorphisms confer susceptibility to SSc and its vascular phenotype, including PAH. METHODS: Four KCNA5 single-nucleotide polymorphisms (SNPs), rs10744676, rs1860420, rs3741930, and rs2284136, were genotyped in a discovery set of 638 SSc patients and 469 controls. In addition, rs10744676 was genotyped in an independent replication sample (938 SSc patients and 564 controls) and in a cohort of 168 patients with different PAH subtypes. RESULTS: The KCNA5 rs10744676 variant was found to be associated with SSc in the discovery sample, with an odds ratio (OR) of 0.62 (95% confidence interval [95% CI] 0.48-0.79, adjusted P = 0.0003) in comparison with controls (C allele frequency 11.4% versus 17.2%). When subphenotypes were investigated, an association was found solely for PAH associated with SSc (OR 0.31 [95% CI 0.13-0.71], adjusted P = 0.04). The other KCNA5 SNPs tested were not associated with any SSc subset. The above association with PAH associated with SSc was replicated in the second set. In the combined population, rs10744676 was strongly associated with PAH associated with SSc in comparison with controls (OR 0.36 [95% CI 0.21-0.63], P = 0.0002). In the independent cohort of patients with PAH, after investigating PAH subtypes, only rs10744676 showed an association with PAH associated with SSc. CONCLUSION: Our results provide the first evidence for an association between the KCNA5 rs10744676 variant and PAH associated with SSc.

Association of the TNFAIP3 rs5029939 variant with systemic sclerosis in the European Caucasian population.

BACKGROUND: TNFAIP3 encodes the ubiquitin-modifying enzyme, a key regulator of inflammatory signalling pathways. Convincing associations between TNFAIP3 variants and autoimmune diseases have been reported. OBJECTIVE: To investigate the association of TNFAIP3 polymorphisms with systemic sclerosis (SSc). METHODS: Three single nucleotide polymorphisms (SNPs) in a set of 1018 patients with SSc and 1012 controls of French Caucasian origin were genotyped. Two intergenic SNPs, rs10499194 and rs6920220, and one located in TNFAIP3 intron 2, rs5029939, were selected. The TNFAIP3 rs5029939 found to be associated with SSc in this first set was then genotyped in a second set of 465 patients with SSc and 182 controls from Germany and 184 patients with SSc and 124 controls from Italy. Pooled odd ratios were calculated by Mantel-Haenszel meta-analysis. RESULTS: The rs5029939 G allele was found to be significantly associated with SSc susceptibility (pooled OR=2.08 (95% CI 1.59 to 2.72); p=1.16×10⁻7), whereas the rs10499194 and rs6920220 variants displayed no association. Only one of the predicted haplotypes investigated in the French sample was significantly associated with SSc (p=8.91×10⁻8), and this haplotype was discriminating only in the presence of the rs5029939 risk allele, suggesting that this SNP tags the association signal. The strongest associations of rs5029939 with subphenotypes, having large magnitudes for complex genetic disorders, were observed for diffuse cutaneous SSc (pooled OR=2.71 (1.94 to 3.79), p=5.2×10⁻9), fibrosing alveolitis (pooled OR=2.26 (1.61 to 3.17), p=2.5×10⁻6) and pulmonary arterial hypertension (pooled OR=3.11 (1.86 to 5.17), p=1.3×10⁻5). CONCLUSION: These results suggest that TNFAIP3 is a genetic susceptibility factor for SSc.

[Therapeutics approach of adult patients with acute and chronic psychotic states: REALITE survey]. / Approche thérapeutique d'une population de patients présentant des troubles psychotiques aigus ou chroniques: enquête REALITE (Recherche Epidémiologique sur l'activité de la Loxapine et ses Indications en Thérapeutique quotidiennE).

A retrospective observational pharmaco-epidemiological survey was conducted during 24 weeks between October 2004 and March 2005 in metropolitan France (384 investigators) to more clearly define the use of loxapine in acute and chronic psychotic states. The objective of this national survey was to specify the clinical and therapeutic profile of patients managed by this antipsychotic in two cohorts of adult patients: one in "acute phase" (prescription of loxapine during the previous 4 weeks), the other in "maintenance phase" (prescription of loxapine for more than 8 weeks). The two groups of the recruited population (1,511 patients) presented identical sociodemographic data. Selection criteria were adapted to the data collected to ensure statistically relevant analysis: 696 patients in acute phase and 633 patients in maintenance phase. The acute phase group was predominantly composed of known patients (82% of patients had a psychotic history) with schizophrenia (47%) or mood disorders (57%) who had already presented acute episodes (an average of 5.4). The current episode consisted of a state of agitation (88%) lasting an average of two weeks, requiring hospitalization (87%), scheduled admission [HDT (admission at the request of another person) in 47.5% of cases and HO (statutory admission) in 40.8% of cases] and prescription of loxapine monotherapy (56%) at a mean daily dose of 177,3 mg. The maintenance phase group comprised a population of known patients (87.5%), schizophrenics (63%), presenting psychotic symptoms (dissociation 82%, delusions 74%) or mood disorders (71%) requiring voluntary hospitalization (78%) for a mean duration of 180 days and a prescription of loxapine monotherapy in 28% of cases at a mean daily dose of 131.6 mg. The loxapine-haloperidol combination (21%) was prescribed more frequently in the second group in the case of chronic disorders; in the other cases, loxapine was coprescribed with the main second generation antipsychotics: risperidone (16%), olanzapine (16%), amisulpride (11%). CGI assessment of the overall study population revealed a marked or very marked clinical improvement with no significant adverse effects in more than 80% of cases.

[Dermatologic manifestations associated with immune reconstitution syndrome in HIV+ patients starting HAART: a retrospective study in French Guiana]. / Manifestations dermatologiques associées au syndrome de restauration immunitaire du patient VIH+ débutant un traitement antirétroviral: etude rétrospective en Guyane française.

Immune reconstitution syndrome (IRIS) is an unusual inflammatory reaction to an opportunistic infection in an HIV-positive patient. This syndrome occurs when immunity is restored in the first months of an effective highly active antiretroviral treatment (HAART). First, we described all patients with a cutaneous form of IRIS. Then, between 1992 and 2004 we conducted a retrospective cohort study comparing Herpes Zoster and Herpes Simplex infections among untreated patients, patients treated by HAART for < or = six months, and patients treated for > six months. We observed three cases of atypical leprosy and three original observations: two of these were fistulisation of lymph node histoplasmosis and tuberculosis, the third one reports the recurrence of a treated cutaneous leishmaniasis. Multivariate analysis showed that, after controlling for age, sex and CD4 counts, patients receiving HAART for < or = six months were more likely to develop Herpes Zoster or herpes simplex infections (p < 0.005). Herpes Simplex and Herpes Zoster infections are the two most frequent dermatological manifestations in our tropical setting. Although mycobacterial infections are more rarely observed than in visceral IRIS, the increased incidence of leprosy may be quite significant when the availability of HAART spreads to developing countries.

[Indications for EEG in mental confusion and behavior problems]. / Indications de l'EEG dan les confusions mentales et les troubles du comportement.

Even in 1998 at the time of brain imaging, EEG recording is undoubtedly useful in clinical psychiatry when a true cerebral disease takes the form of an acute psychiatric disorder. Though the real place of EEG recording cannot be yet accurately quantified, it may help guide the diagnosis, as it is of either positive (ie, confirming the diagnosis via additional information) or negative (ie, rejecting various etiologies) value. Most of the time, only the former is considered in published studies. The clinical value of EEG recording in psychiatry emergency unit is therefore still not clearly established. The study of patients admitted during two years in the emergency unit at Sainte-Anne hospital (Paris, France) does not bring new conclusions, mainly because of bias in the modalities of admission and follow-up. As well, the role of EEG recording for the diagnosis of non-psychiatric diseases in psychiatry emergency units cannot be defined today. The authors review clinical situations where EEG recording is still highly advisable.

[A case of coinfection by Balantidium coli and HIV in French Guiana]. / Un cas de co-infection par Balantidium coli et VIH en Guyane Française.

A case of balantidial dysentery is reported in a patient infected with the HIV in French Guiana. This case is the first described in medical literature. The patient presented also a disseminated histoplasmosis. Immunosuppression probably favoured the evolution of asymptomatic carriage to clinical dysentery. This clinical case did not present any complications. Treatment with doxycycline had to be carried out for 20 days in order to obtain a clinical and parasitological cure.

[Histoplasmosis due to Histoplasma capsulatum capsulatum and HIV infection]. / Histoplasmose à Histoplasma capsulatum capsulatum et infection à VIH.

PURPOSE: Histoplasmosis due to Histoplasma capsulatum is a granulomatous fungic infection which appears opportunistic and disseminated in immunocompromised patients, especially among HIV patients in whom it can lead to death. Histoplasmosis is endemic in numerous areas worldwide, but in Europe most of the cases reported are imported. We describe the clinical features and the available diagnosis methods issued from our experience in French Guyana. METHODS: Contamination occurs by inhalation of spores contained in dust. Most endemic areas are located on the American continent, including the French West Indies, where the incidence of histoplasmosis among HIV patients in French Guyana varies from 1.2 to 2.2% per year. In non-immunocompromised patients, histoplasmosis is asymptomatic most of the time. In HIV patients, the disseminated form is common and may occur many years after exposure to the fungus. RESULTS: Non-specific symptoms, similar to those of either tuberculosis or other opportunistic infections, may reveal disseminated histoplasmosis in patients with AIDS. Early treatment (amphotericin B or itraconazole) is effective; however, it should be followed by a lifelong antifungic treatment (itraconazole) to prevent relapse. CONCLUSION: The infection should be suspected in any febrile HIV-infected patient with CD4 blood cell count < 200/mm3, if he/she ever travelled in an endemic zone. Direct examination of smear relating to clinical symptoms help guide diagnosis, while culture will confirm it after at least 4 weeks. Efficient serologic techniques for HIV-infected patients are not available in Europe.

[Hereditary multiple exostoses after 40 years of development: a case report]. / Maladie des exostoses multiples après 40 ans d'évolution: à propos d'un cas.

INTRODUCTION: Hereditary multiple exostoses is an autosomal dominant skeletal disorder with genetic heterogeneity and an estimated prevalence of 1/50,000 in western countries. Malignant degeneration is a rare (about 2%) but classical complication in patients with hereditary multiple exostoses. At least 3 loci identified as EXT 1, EXT 2 and EXT 3 are involved in this skeletal disease. EXEGESIS: The case of a 45-year old man is described with 15 years follow-up after resection of a well-differentiated chondrosarcoma (grade I), which arose from a right posterior pelvic exostosis. The observed radiological lesions remained relatively stable until now. The genetic mutation which is responsible for the disease was determined at the locus EXT 1. CONCLUSION: The present case report illustrates the natural history of hereditary multiple exostoses, especially since the patient underwent a malignant degeneration which could be resected without recurrence. The results of the genetic analysis contributed to the understanding of the pathophysiology of the disease.

[The practice of restraint in a psychiatric emergency unit]. / Pratique de la contention dans un service d'urgences psychiatriques.

The practice of physical restraint is relatively frequent in medical emergency and geriatric units. Its use in psychiatry is controversial. Although distinct, it is often associated with seclusion, as a response to or prevention of agitated mentally ill patients'behavior. A detailed review of the literature shows the scarceness of work defining the exclusive use of restraint without seclusion. We report a naturalistic study over 6 Months, covering 76 cases having required restraint. The study of the international literature concerns nursing care, geriatric, child-adolescent psychiatric and adult psychiatric reviews. The restraint is a usual practice in general care like emergency, intensive care or geriatric units in order to prevent the patients from falling or to administrate certain care. Legal action has been reported as a consequence of lack of information or agreement of the family. The psychiatric use of restraint is conceived as an additional measure to seclusion, which is a controversial procedure from a therapeutic point of view as well as because of its long duration of application. The practice of restraint described in French literature, from Pinel (in to Daumézon and from French hospital regulations to "transparency forms", seems to be more easily accepted for its short duration and its careful prescription in order to maintain relations with the patients, including agitated children. We made a 6 Months retrospective study in a Parisian psychiatric emergency unit receiving an average of 30 patients a day. The rate of restraint is 1.4%. The objective was to describe the main clinical, epidemiological and situational characteristics and to define quality criteria concerning restraint regarding to the existing standards. We had at our disposal a restraint protocol in order to avoid its prescription as a punishment or for the comfort or the convenience of an insufficient staff. The decision of the restraint is directly prescribed by a physician or decided in emergency by the nurses and then rapidly confirmed by medical prescription. In short, most restrained patients are male, the average age is 32 Years old, and the diagnoses associated with restraint in order of frequency are schizophrenia, personality disorders, acute psychotic episodes, manic episodes and toxic abuses. The main early-warning signs are aggressiveness, delusions, opposition, paranoiac thoughts and distrust. The average duration is 2 hours with continuous clinical supervision and a relational contact maintained. Our study confirms the notion of cumulate restraint days. Actually, 43% of the restraints happen on the same day as others do. The high rate on those days could be as Fischer hypothesized the result of instinctive, aggressive and sexual release of the staff, as well as the consequence of an increase in anxiety and agitation of the other patients. The legal framework is more the duty of assistance to a person in danger than constrained hospitalization, which is not systematically pronounced. No injury or somatic complication occurred during restraint. Neither complaint from the patient or his family nor sick leave of staff was recorded. The specific use of restraint can be compared to the existing standards for using the seclusion room. Among those standards only 1 of 23 criteria was not verified. The others was applicable or without object. The therapeutic use of restraint requires the development of specific quality standards, and the existing criteria concerning seclusion represent a necessary but insufficient answer. We emphasize the need to take into account the early warning signs, a response to the cumulative restraint days, as well as a satisfaction study on patients and the feasibility of such a study in an emergency service.

A refined molecular taxonomy of breast cancer.

The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derived from relatively small initial patient populations. We analyzed the transcriptomes of 537 breast tumors using three unsupervised classification methods. A core subset of 355 tumors was assigned to six clusters by all three methods. These six subgroups overlapped with previously defined molecular classes of breast cancer, but also showed important differences, notably the absence of an ERBB2 subgroup and the division of the large luminal ER+ group into four subgroups, two of them being highly proliferative. Of the six subgroups, four were ER+/PR+/AR+, one was ER-/PR-/AR+ and one was triple negative (AR-/ER-/PR-). ERBB2-amplified tumors were split between the ER-/PR-/AR+ subgroup and the highly proliferative ER+ LumC subgroup. Importantly, each of these six molecular subgroups showed specific copy-number alterations. Gene expression changes were correlated to specific signaling pathways. Each of these six subgroups showed very significant differences in tumor grade, metastatic sites, relapse-free survival or response to chemotherapy. All these findings were validated on large external datasets including more than 3000 tumors. Our data thus indicate that these six molecular subgroups represent well-defined clinico-biological entities of breast cancer. Their identification should facilitate the detection of novel prognostic factors or therapeutical targets in breast cancer.