Experiences of men with breast cancer: an exploratory focus group study

Management and care of men with breast cancer is based on that developed for women. Our study reports that men have specific issues regarding certain aspects of their breast cancer experience, including diagnosis, disclosure, support and gender-specific information, and offers suggestions for improved patient care

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer

International audienceBACKGROUND: This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma. METHODS: First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT-qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers. RESULTS: GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph node-positive (pN+) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN+ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN+ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients. CONCLUSIONS: Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN+ patients

Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells

BACKGROUND: Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells. Despite this promising feature, TRAIL resistance observed in cancer cells seriously challenged the use of TRAIL as a death ligand in gene therapy. The current dispute concerns whether or not TRAIL receptor expression pattern is the primary determinant of TRAIL sensitivity in cancer cells. This study investigates TRAIL receptor expression pattern and its connection to TRAIL resistance in breast cancer cells. In addition, a DcR2 siRNA approach and a complementary gene therapy modality involving IKK inhibition (AdIKKβKA) were also tested to verify if these approaches could sensitize MCF7 breast cancer cells to adenovirus delivery of TRAIL (Ad5hTRAIL). METHODS: TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells. RESULTS: MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKKβKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4 expression. Furthermore, a DcR2 siRNA approach lowered TRAIL-R4 expression on surface and this sensitized MCF7 cells to TRAIL. CONCLUSION: The expression of TRAIL-R4 decoy receptor appeared to be well correlated with TRAIL resistance encountered in breast cancer cells. Both adenovirus mediated IKKβKA expression and a DcR2 siRNA approach sensitized MCF7 breast cancer cells to TRAIL

Comparison of Functional Proteomic Analyses of Human Breast Cancer Cell Lines T47D and MCF7

T47D and MCF7 are two human hormone-dependent breast cancer cell lines which are widely used as experimental models for in vitro and in vivo (tumor xenografts) breast cancer studies. Several proteins involved in cancer development were identified in these cell lines by proteomic analyses. Although these studies reported the proteomic profiles of each cell line, until now, their differential protein expression profiles have not been established. Here, we used two-dimensional gel and mass spectrometry analyses to compare the proteomic profiles of the two cell lines, T47D and MCF7. Our data revealed that more than 164 proteins are differentially expressed between them. According to their biological functions, the results showed that proteins involved in cell growth stimulation, anti-apoptosis mechanisms and cancerogenesis are more strongly expressed in T47D than in MCF7. These proteins include G1/S-specific cyclin-D3 and prohibitin. Proteins implicated in transcription repression and apoptosis regulation, including transcriptional repressor NF-X1, nitrilase homolog 2 and interleukin-10, are, on the contrary, more strongly expressed in MCF7 as compared to T47D. Five proteins that were previously described as breast cancer biomarkers, namely cathepsin D, cathepsin B, protein S100-A14, heat shock protein beta-1 (HSP27) and proliferating cell nuclear antigen (PCNA), are found to be differentially expressed in the two cell lines. A list of differentially expressed proteins between T47D and MCF7 was generated, providing useful information for further studies of breast cancer mechanisms with these cell lines as models

Breast cancer risk factor knowledge among nurses in teaching hospitals of Karachi, Pakistan: a cross-sectional study

BACKGROUND: Breast cancer is the most common cancer among women in both the developed and the developing world. The incidence of breast cancer in Karachi, Pakistan is 69.1 per 100,000 with breast cancer presentation in stages III and IV being common (≥ 50%). The most pragmatic solution to early detection lies in breast cancer education of women. Nurses constitute a special group having characteristics most suited for disseminating breast cancer information to the women. We assessed the level of knowledge of breast cancer risk factors among registered female nurses in teaching hospitals of Karachi. We also identified whether selected factors among nurses were associated with their knowledge of breast cancer risk factors, so that relevant measures to improve knowledge of nurses could be implemented. METHODS: A cross-sectional survey was conducted in seven teaching hospitals of Karachi using stratified random sampling with proportional allocation. A total of 609 registered female nurses were interviewed using a structured questionnaire adapted from the Stager's Comprehensive Breast Cancer Knowledge Test. Knowledge of breast cancer risk factors was categorized into good, fair and poor categories. Ordinal regression was used to identify factors associated with risk knowledge among nurses. RESULTS: Thirty five percent of nurses had good knowledge of risk factors. Graduates from private nursing schools (aOR = 4.23, 95% CI: 2.93, 6.10), nurses who had cared for breast cancer patients (aOR = 1.41, 95% CI: 1.00, 1.99), those having received a breast examination themselves (aOR = 1.56, 95% CI: 1.08, 2.26) or those who ever examined a patient's breast (aOR = 1.87, 95% CI: 1.34, 2.61) were more likely to have good knowledge. CONCLUSION: A relatively small proportion of the nursing population had good level of knowledge of the breast cancer risk factors. This knowledge is associated with nursing school status, professional breast cancer exposure and self history of clinical breast examination. Since only about one-third of the nurses had good knowledge about risk factors, there is a need to introduce breast cancer education in nursing schools particularly in the public sector. Continuing nursing education at the workplace can be of additional benefit

Genetic Variants at Chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 Influence the Risk of Breast Cancer in Men

Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS) have recently identified common single nucleotide polymorphisms (SNPs) that influence female breast cancer risk; 12 of these have been independently replicated. To examine if these variants contribute to male breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls. Five SNPs showed a statistically significant association with male breast cancer: rs13387042 (2q35) (odds ratio (OR)  = 1.30, p = 7.98×10−4), rs10941679 (5p12) (OR = 1.26, p = 0.007), rs9383938 (6q25.1) (OR = 1.39, p = 0.004), rs2981579 (FGFR2) (OR = 1.18, p = 0.03), and rs3803662 (TOX3) (OR = 1.48, p = 4.04×10−6). Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs—rs13387042 (2q35), rs3803662 (TOX3), and rs6504950 (COX11)—showed significant differences in ORs (p<0.05) between sexes. Breast cancer is a heterogeneous disease; the relative risks associated with loci identified to date show subtype and, based on these data, gender specificity. Additional studies of well-defined patient subgroups could provide further insight into the biological basis of breast cancer development

Association of daily tar and nicotine intake with incident myocardial infarction: Results from the population-based MONICA/KORA Augsburg Cohort Study 1984 - 2002

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking has been shown to be one of the most important risk factors for cardiovascular diseases. However, little is known about cumulative effects of daily tar and nicotine intake on the risk of incident myocardial infarction (MI) so far. To bridge this gap, we conducted an analysis in a large prospective study from Southern Germany investigating associations of daily tar and nicotine intake with an incident MI event.</p> <p>Methods</p> <p>The study was based on 4,099 men and 4,197 women participating in two population-based MONICA Augsburg surveys between 1984 and 1990 and followed up within the KORA framework until 2002. During a mean follow-up of 13.3 years, a number of 307 men and 80 women developed an incident MI event. Relative risks were calculated as hazard ratios (HRs) estimated by Cox proportional hazards models adjusted for cardiovascular risk factors.</p> <p>Results</p> <p>In the present study, male regular smokers consumed on average more cigarettes per day than female regular smokers (20 versus 15) and had a higher tar and nicotine intake per day. In men, the MI risk compared to never-smokers increased with higher tar intake: HRs were 2.24 (95% CI 1.40-3.56) for 1-129 mg/day, 2.12 (95% CI 1.37-3.29) for 130-259 mg/day and 3.01 (95% CI 2.08-4.36) for ≥ 260 mg/day. In women, the corresponding associations were comparable but more pronounced for high tar intake (HR 4.67, 95% CI 1.76-12.40). Similar associations were observed for nicotine intake.</p> <p>Conclusions</p> <p>The present study based on a large population-based sample adds important evidence of cumulative effects of tar and nicotine intake on the risk of incident MI. Even low or medium tar and nicotine intake revealed substantial risk increases as compared to never-smokers. Therefore, reduction of tar and nicotine contents in cigarettes cannot be seen as a suitable public health policy in preventing myocardial infarction.</p

Socioeconomic inequalities in cause specific mortality among older people in France

<p>Abstract</p> <p>Background</p> <p>European comparative studies documented a clear North-South divide in socioeconomic inequalities with cancer being the most important contributor to inequalities in total mortality among middle aged men in Latin Europe (France, Spain, Portugal, Italy). The aim of this paper is to investigate educational inequalities in mortality by gender, age and causes of death in France, with a special emphasis on people aged 75 years and more.</p> <p>Methods</p> <p>We used data from a longitudinal population sample that includes 1% of the French population. Risk of death (total and cause specific) in the period 1990-1999 according to education was analysed using Cox regression models by age group (45-59, 60-74, and 75+). Inequalities were quantified using both relative (ratio) and absolute (difference) measures.</p> <p>Results</p> <p>Relative inequalities decreased with age but were still observed in the oldest age group. Absolute inequalities increased with age. This increase was particularly pronounced for cardiovascular diseases. The contribution of different causes of death to absolute inequalities in total mortality differed between age groups. In particular, the contribution of cancer deaths decreased substantially between the age groups 60-74 years and 75 years and more, both in men and in women.</p> <p>Conclusions</p> <p>This study suggests that the large contribution of cancer deaths to the excess mortality among low educated people that was observed among middle aged men in Latin Europe is not observed among French people aged 75 years and more. This should be confirmed among other Latin Europe countries.</p

The state-of-the-art determination of urinary nucleosides using chromatographic techniques “hyphenated” with advanced bioinformatic methods

Over the last decade metabolomics has gained increasing popularity and significance in life sciences. Together with genomics, transcriptomics and proteomics, metabolomics provides additional information on specific reactions occurring in humans, allowing us to understand some of the metabolic pathways in pathological processes. Abnormal levels of such metabolites as nucleosides in the urine of cancer patients (abnormal in relation to the levels observed in healthy volunteers) seem to be an original potential diagnostic marker of carcinogenesis. However, the expectations regarding the diagnostic value of nucleosides may only be justified once an appropriate analytical procedure has been applied for their determination. The achievement of good specificity, sensitivity and reproducibility of the analysis depends on the right choice of the phases (e.g. sample pretreatment procedure), the analytical technique and the bioinformatic approach. Improving the techniques and methods applied implies greater interest in exploration of reliable diagnostic markers. This review covers the last 11 years of determination of urinary nucleosides conducted with the use of high-performance liquid chromatography in conjunction with various types of detection, sample pretreatment methods as well as bioinformatic data processing procedures