Membrane lipidomics in schizophrenia patients: a correlational study with clinical and cognitive manifestations.

Schizophrenia is a severe mental condition in which several lipid abnormalities-either structural or metabolic-have been described. We tested the hypothesis that an abnormality in membrane lipid composition may contribute to aberrant dopamine signaling, and thereby symptoms and cognitive impairment, in schizophrenia (SCZ) patients. Antipsychotic-medicated and clinically stable SCZ outpatients (n=74) were compared with matched healthy subjects (HC, n=40). A lipidomic analysis was performed in red blood cell (RBC) membranes examining the major phospholipid (PL) classes and their associated fatty acids (FAs). Clinical manifestations were examined using the positive and negative syndrome scale (PANSS). Cognitive function was assessed using the Continuous Performance Test, Salience Attribution Test and Wisconsin Card Sorting Test. Sphingomyelin (SM) percentage was the lipid abnormality most robustly associated with a schizophrenia diagnosis. Two groups of patients were defined. The first group (SCZ c/SM-) is characterized by a low SM membrane content. In this group, all other PL classes, plasmalogen and key polyunsaturated FAs known to be involved in brain function, were significantly modified, identifying a very specific membrane lipid cluster. The second patient group (SCZ c/SM+) was similar to HCs in terms of RBC membrane SM composition. Compared with SCZ c/SM+, SCZ c/SM- patients were characterized by significantly more severe PANSS total, positive, disorganized/cognitive and excited psychopathology. Cognitive performance was also significantly poorer in this subgroup. These data show that a specific RBC membrane lipid cluster is associated with clinical and cognitive manifestations of dopamine dysfunction in schizophrenia patients. We speculate that this membrane lipid abnormality influences presynaptic dopamine signaling.

Breast-conserving treatment for ductal carcinoma in situ: Impact of boost and tamoxifen on local recurrences.

PURPOSE: Ductal carcinoma in situ represents 15 to 20% of all breast cancers. Breast-conserving surgery and whole breast irradiation was performed in about 60% of the cases. This study reports local recurrence rates in patients with ductal carcinoma in situ treated by breast-conserving surgery and whole breast irradiation with or without boost and/or tamoxifen and compares different therapeutic options in two European countries. PATIENTS AND METHODS: From 1998 to 2007, 819 patients with pure ductal carcinoma in situ were collected, both in France (266) and Italy (553). Median age was 56. All underwent breast-conserving surgery and whole breast irradiation; 391 (48%) received a boost (55% in France and 45% in Italy, P=0.017) and 173 (22.5%) tamoxifen (4.5% in France and 32% in Italy, P<0.0001). RESULTS: With a 90-month median follow-up, there were 51 local recurrences (6.2%), including 27 invasive (53%). The 5- and 10-year local recurrence rates were 4% and 8.6%. Two patients developed axillary recurrence and 12 (1.5%) metastases (seven after invasive local recurrence); 41 (5%) patients had contralateral breast cancer. In the multivariate analysis, high nuclear grade and lack of tamoxifen are the most powerful predictors of local recurrence, with 2.6 (95% confidence interval [95% CI]: 1.74-3.89, P=0.0012) and 2.85 (95% CI: 1.42-5.72, P=0.04) odds ratio (OR) estimates, respectively. Age, margin status and boost did not influence local recurrence rates. CONCLUSIONS: This study confirms the ductal carcinoma in situ treatment heterogeneity among countries and the unfavourable prognostic role of nuclear grade. Tamoxifen reduces local recurrence rates and might be considered for some subgroups of patients, but further confirmation is required. The boost usefulness still remains unclear.

Male breast cancer. Evolution of treatment and prognostic factors. Analysis of 489 cases.

BACKGROUND: Infiltrating MBC represents less than 1% of all male cancers. Our study details clinico-pathological features, treatments and prognostic factors in a large French cohort. MATERIAL AND METHODS: Four hundred and eighty-nine patients were collected from 1990 to 2005. Median age was 66 years (34% over 70 years) and median follow-up 58 months. RESULTS: According to TN classification, we found T(1): 39%, T(2): 41%, T(3)T(4): 9%, T(x): 11% and N(1)N(2): 27%. Lumpectomy (L) and mastectomy (M) were performed in 8.6% and 91.4% of the cases. Axillary dissection (AD), sentinel node biopsy or both were performed in 90%, 2% and 5% of the cases, respectively. Ninety-five percent of tumours were ductal carcinomas; 47% were pT(1), 20% pT(2) and 33% pT(3)-T(4). Axillary nodal involvement was present in 52.8% cases. ER and PgR were positive in 92% and 89% cases. Radiotherapy (RT) was performed in 85% of the patients. Hormonal treatment (HT) was delivered in 72% of the cases. Tamoxifen and aromatase inhibitors were used in 85% and 12% of the cases; 34% of the patients received chemotherapy (CT). Local recurrence (LR), nodal recurrences (NR) and metastases occurred in 2%, 5% and 22% of the cases; 2% and 10% developed contralateral BC and second cancer. The 5- and 10-year overall survival (OS) rates were 81% and 59%; disease-specific survivals (DSS) were 89% and 72%. Death causes were BC 56%, second cancer 8%, complications 3%, intercurrent disease 15% and unknown 18%. In a univariate analysis, metastatic risk factors were T stage (T1: 19%, T(2): 26%, T(3)T(4): 40%; p=0.013), pN status (pN(0): 12% pN(1-3): 26% pN(>3): 44%; p<0.0001) and presence of locoregional recurrence (62% versus 18% p<0.0001). In a multivariate analysis, axillary nodal involvement and high SBR remain prognostic factors. CONCLUSION: Earlier diagnosis and wide use of adjuvant treatments (RT/HT/CT) widely decreased LR and increased survival rates in MBC, reaching female ones. Prognostic factors were also very similar to female ones.