No association found between CYP2D6 genotype and early breast cancer events in tamoxifen-treated patients.

Background. CYP2D6 is considered the key enzyme in tamoxifen metabolism. Several studies have investigated the relationship between the CYP2D6 genotype and tamoxifen treatment outcome, with discrepant results. CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy may account for some of the discrepancies. We examined the association between CYP2D6 genotype and early breast cancer events in tamoxifen-treated breast cancer patients, in relation to CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy. Material and methods. Pre- and postoperative questionnaires on lifestyle and concomitant medications were completed by 634 primary breast cancer patients between 2002 and 2008, among whom 333 patients had ER-positive tumors and received tamoxifen. CYP2D6*3, *4, *6, *10 and *41 were genotyped. Information on clinical data, breast cancer events, and tumor characteristics was obtained from patients' charts, population registries, the Regional Tumor Registry, and pathology reports. Results. Median follow-up was 4.9 years. Neither poor metabolizers (adjusted HR 0.50; 95% CI 0.07-3.82) nor intermediate metabolizers (adjusted HR 1.00; 95% CI 0.47-2.11) had an increased risk of early breast cancer events when compared with extensive metabolizers. CYP2D6 activity score (taking into account genotype and CYP2D6 inhibitor use) was not associated with early breast cancer events (LogRank, Ptrend = 0.44). Conclusions. CYP2D6 genotype was not associated with tamoxifen treatment outcome, even when CYP2D6 inhibitor use, aromatase inhibitor use, or chemotherapy was taken into account. CYP2D6 genotype may be of minor importance for tamoxifen-treated patients in Scandinavia

Androgen receptor genotypes predict response to endocrine treatment in breast cancer patients.

Background:The androgen receptor (AR) is frequently expressed in breast cancers. The AR genotype may affect disease-free survival and response to endocrine therapy.Methods:In all, 634 women undergoing breast cancer surgery between 2002 and 2008 were followed until 30 June 2010. Six haplotype-tagging single-nucleotide polymorphisms in the AR, and the resulting AR diplotypes, were examined in relation to breast cancer patient characteristics, tumour characteristics, disease-free survival, and response to endocrine treatment.Results:Five common AR diplotypes were found. Seventeen rare variants were combined into a composite group. The resulting six AR diplotype groups were clustered into two subgroups, groups A (n=128) and B (n=499), with three diplotypes in each. Patients in group B had larger total breast volume (P=0.024), higher body mass index (BMI) (P=0.050), more axillary lymph node involvement (P(trend)=0.020), and higher histological grade (P(trend)=0.031). There were 59 breast cancer events in the 569 patients with invasive cancers and no preoperative treatment. Patients in group B also had shorter disease-free survival (P=0.037) than patients in group A. Among patients in group B with oestrogen receptor α positive tumours, tamoxifen (TAM) treatment was associated with longer disease-free survival (P=0.008), while treatment with aromatase inhibitors (AIs) was not (P=0.94). Response to endocrine treatment could not be predicted based on BMI, suggesting that the effect of AR diplotypes went beyond that of a higher BMI.Conclusion:A marker for a group of patients who responded to TAM, but not to AIs, was identified. If this finding is confirmed, AR genotyping may provide useful information for selection of endocrine treatment of breast cancer patients.British Journal of Cancer advance online publication, 27 October 2011; doi:10.1038/bjc.2011.441 www.bjcancer.com

Excessive milk production during breast-feeding prior to breast cancer diagnosis is associated with increased risk for early events

Breast-feeding is a known protective factor against breast cancer. Breast-feeding duration is influenced by hormone levels, milk production, and lifestyle factors. The aims were to investigate how breast-feeding duration and milk production affected tumor characteristics and risk for early breast cancer events in primary breast cancer patients. Between 2002 and 2008, 634 breast cancer patients in Lund, Sweden, took part in an ongoing prospective cohort study. Data were extracted from questionnaires, pathology reports, and patients’ charts from 592 patients without preoperative treatment. Breast-feeding duration ≤12 months of the first child was associated with higher frequency of ER+/PgR+ tumors (P=0.02). Median follow-up time was 4.9 years. Higher risk for early events was observed for breast-feeding duration of first child >12 months (LogRank P=0.001), total breast-feeding duration >12 months (LogRank P=0.008), as well as ‘excessive milk production’ during breast-feeding of the first child (LogRank P=0.001). Patients with ‘almost no milk production’ had no events. In a multivariable model including both ‘excessive milk production’ and breast-feeding duration of the first child >12 months, both were associated with a two-fold risk for early events, adjusted HRs 2.33 (95% CI: 1.25-4.36) and 2.39 (0.97-5.85), respectively, while total breast-feeding duration was not. ‘Excessive milk production’ was associated with a two-fold risk of early distant metastases, adjusted HR 2.59 (1.13-5.94), but not duration. In conclusion, ‘excessive milk production’ during breast-feeding was associated with higher risk for early events independent of tumor characteristics, stressing the need to consider host factors in the evaluation of prognostic markers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-298) contains supplementary material, which is available to authorized users

The Effect of Dietary Fish Oil in addition to Lifestyle Counselling on Lipid Oxidation and Body Composition in Slightly Overweight Teenage Boys

Objective. n-3 long-chain polyunsaturated fatty acids (LCPUFAs) have shown potential to increase lipid oxidation and prevent obesity. Subjects. Seventy-eight boys aged 13–15 y with whole-body fat% of 30 ± 9% were randomly assigned to consume bread with fish oil (FO) (1.5 g n-3 LCPUFA/d) or vegetable oil for 16 weeks. All boys were counselled to improve diet and exercise habits. Results. Lifestyle counselling resulted in decreased sugar intake but did not change the physical activity level. Whole-body fat% decreased 0.7 ± 2.5% and 0.6 ± 2.2%, resting metabolic rate after the intervention was 7150 ± 1134 kJ/d versus 7150 ± 1042 kJ/d, and the respiratory quotient was 0.89 ± 0.05 versus 0.88 ± 0.05, in the FO and control group, respectively. No group differences were significant. Conclusion. FO-supplementation to slightly overweight teenage boys did not result in beneficial effects on RMR, lipid oxidation, or body composition

VISIR federation: Initial building steps (PILAR experience – work in progress)

Collaborative working as well as sharing resources and knowledge represent key points in today's development in all fields, including education. Know-how transfer and collaboration in learning and teaching are aspects promoted and sustained by institutional management as well as the European initiatives. Thus, leading to the idea of a federation which will facilitate engineering education. A consortium formed by five European universities decided to join efforts to provide to the community a federation, which could be used by different stakeholders interest in teaching, learning or developing new skills in the field of electronics. The proposed remote system, Virtual Instruments System in Reality, or VISIR in short, offers the possibility of working with real equipment and obtain the real-world/ real-time measurements. By developing such a VISIR federation some of the constraints of using remote labs, the ones associated with development and maintenance costs, and scalability, will be minimized.info:eu-repo/semantics/publishedVersio

Given breast cancer, does breast size matter? Data from a prospective breast cancer cohort.

PURPOSE: Body mass index (BMI), waist-to-hip ratio (WHR), and tumor characteristics affect disease-free survival. Larger breast size may increase breast cancer risk, but its influence on disease-free survival is unclear. The purpose of this study was to elucidate whether breast size independently influenced disease-free survival in breast cancer patients. METHODS: Body measurements were obtained preoperatively from 772 breast cancer patients in a population-based ongoing cohort from southern Sweden. The research nurse measured breast volumes with plastic cups used by plastic surgeons doing breast reductions. Clinical data were obtained from patient charts and pathology reports. RESULTS: Patients with a BMI ≥ 25 kg/m(2) had larger tumors (p 0.85 had larger tumors (p = 0.013), more advanced histological grade (p = 0.0016), and more axillary nodal involvement (p = 0.012). Patients with right + left breast volume ≥ 850 mL were more likely to have larger tumor sizes (p = 0.018), more advanced histological grade (p = 0.031), and more axillary nodal involvement (p = 0.025). There were 62 breast cancer events during the 7-year follow-up. Breast volume ≥ 850 mL was associated with shorter disease-free survival (p = 0.004) and distant metastasis-free survival (p = 0.001) in patients with estrogen receptor (ER)-positive tumors independent of other anthropometric measurements and age. In patients with ER-positive tumors, breast size was an independent predictor of shorter disease-free (HR 3.64; 95 % CI 1.42-9.35) and distant metastasis-free survival (HR 6.33; 95 %CI 1.36-29.43), adjusted for tumor characteristics, BMI, age, and treatment. CONCLUSION: A simple and cheap anthropometric measurement with standardized tools may help identify a subgroup of patients in need of tailored breast cancer therapy

(68)Ga-labeled superparamagnetic iron oxide nanoparticles (SPIONs) for multi-modality PET/MR/Cherenkov luminescence imaging of sentinel lymph nodes.

The aim of this study was to develop (68)Ga-SPIONs for use as a single contrast agent for dynamic, quantitative and high resolution PET/MR imaging of Sentinel Lymph Node (SLN). In addition (68)Ga enables Cherenkov light emission which can be used for optical guidance during resection of SLN. SPIONs were labeled with (68)Ga in ammonium acetate buffer, pH 5.5. The labeling yield and stability in human serum were determined using instant thin layer chromatography. An amount of 0.07-0.1 mL (~5-10 MBq, 0.13 mg Fe) of (68)Ga-SPIONs was subcutaneously injected in the hind paw of rats. The animals were imaged at 0-3 h and 25 h post injection with PET/CT, 9.4 T MR and CCDbased Cherenkov optical systems. A biodistribution study was performed by dissecting and measuring the radioactivity in lymph nodes, kidneys, spleen, liver and the injection site. The labeling yield was 97.3 ± 0.05% after 15 min and the (68)Ga-SPIONs were stable in human serum. PET, MR and Cherenkov luminescence imaging clearly visualized the SLN. Biodistribution confirmed a high uptake of the (68)Ga-SPIONs within the SLN. We conclude that generator produced (68)Ga can be labeled to SPIONs. Subcutaneously injected (68)Ga-SPIONs can enhance the identification of the SLNs by combining sensitive PET and high resolution MR imaging. Clinically, hybrid PET/MR cameras are already in use and (68)Ga-SPIONs have a great potential as a single-dose, tri-modality agent for diagnostic imaging and potential Cherenkov luminescent guided resection of SLN

High-resolution in vivo imaging of xylem-transported CO2 in leaves based on real-time 11C-tracing

Plant studies using the short-lived isotope C-11 to label photosynthate via atmospheric carbon dioxide (CO2), have greatly advanced our knowledge about the allocation of recent photosynthate from leaves to sinks. However, a second source for photosynthesis is CO2 in the transpiration stream, coming from respiration in plant tissues. Here, we use in vivo tracing of xylem-transported (CO2)-C-11 to increase our knowledge on whole plant carbon cycling.We developed a newmethod for in vivo tracing of xylem-transported CO2 in excised poplar leaves using C-11 in combination with positron emission tomography (PET) and autoradiography. To show the applicability of both measurement techniques in visualizing and quantifying CO2 transport dynamics, we administered the tracer via the cut petiole and manipulated the transport by excluding light or preventing transpiration. Irrespective of manipulation, some tracer was found in main and secondary veins, little of it was fixed in minor veins or mesophyll, while most of it diffused out the leaf. Transpiration, phloem loading and CO2 recycling were identified as mechanisms that could be responsible for the transport of internal CO2. Both C-11-PET and autoradiography can be successfully applied to study xylem-transported CO2, toward better understanding of leaf and plant carbon cycling, and its importance in different growing conditions