Primary Relapse Site Pattern In Women With Triple-negative Breast Cancer.

Despite the remarkable improvements in breast cancer (BC) characterization, accurate prediction of BC clinical behavior is often still difficult to achieve. Some studies have investigated the association between the molecular subtype, namely the basal-like BC and the pattern of relapse, however only few investigated the association between relapse pattern and immunohistochemical defined triple-negative breast cancers (TNBCs). The aim of this study was to evaluate the pattern of relapse in patients with TNBC, namely the primary distant relapse site. One-hundred twenty nine (129) invasive breast carcinomas with follow-up information were classified according to the molecular subtype using immunohistochemistry for ER, PgR and Her2. The association between TNBC and distant relapse primary site was analyzed by logistic regression. Using multivariate logistic regression analysis patients with TNBC displayed only 0.09 (95% CI: 0.00-0.74; p=0.02) the odds of the non-TNBC patients of developing bone primary relapse. Regarding visceral and lymph-node relapse, no differences between in this cohort were found. Though classically regarded as aggressive tumors, TNBCs rarely development primary relapse in bone when compared to non-TNBC, a clinical relevant fact when investigating a metastasis of an occult or non-sampled primary BC.

Polymorphism In Lep And Lepr May Modify Leptin Levels And Represent Risk Factors For Thyroid Cancer.

Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98 ng/mL) than those with AG genotype (10.07 ± 0.60 ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59 ng/mL) than the subjects with GG genotype (9.52 ± 0.79 ng/mL; P < 0.05). A multivariate logistic regression adjusted for gender, age, and BMI showed that the AG genotype of rs7799039 was an independent risk for DTC (OR, 11.689; P = 0.0183; 95% CI, 1.516-90.119). Similarly, AG and GG genotypes of rs1137101 increased the susceptibility to DTC (OR, 3.747; P = 0.027; 95% CI, 1.161-12.092 and OR, 5.437; P = 0.013; 95% CI, 1.426-20.729). Conclusions. We demonstrated that rs7799039 and rs2167270 polymorphisms modify the serum leptin concentrations in patients with DTC. Furthermore, polymorphisms rs7799039 and rs1137101 increase the risk of DTC development, although they do not correlate with tumor aggressiveness.

Survival and quality of life of patients with oral and oropharyngeal cancer at 1-year follow-up of tumor resection

OBJECTIVE: This study aimed to assess the survival and life quality evolution of patients subjected to surgical excision of oral and oropharyngeal squamous cell carcinoma. MATERIAL AND METHODS: Forty-seven patients treated at a Brazilian healthcare unit specialized in head and neck surgery between 2006 and 2007 were enrolled in the study. The gathering of data comprised reviewing hospital files and applying the University of Washington Quality of Life (UW-QOL) questionnaire previously and 1 year after the surgery. Comparative analysis used Poisson regression to assess factors associated with survival and a paired t-test to compare preoperative and 1-year postoperative QOL ratings. RESULTS: 1 year after surgery, 7 patients were not found (dropout of the cohort); 15 had died and 25 fulfilled the UW-QOL again. The risk of death was associated with having regional metastasis previously to surgery (relative risk=2.18; 95% confidence interval=1.09-5.17) and tumor size T3 or T4 (RR=2.30; 95%CI=1.05-5.04). Survivors presented significantly (p<0.05) poorer overall and domain-specific ratings of quality of life. Chewing presented the largest reduction: from 74.0 before surgery to 34.0 one year later. Anxiety was the only domain whose average rating increased (from 36.0 to 70.7). CONCLUSIONS: The prospective assessment of survival and quality of life may contribute to anticipate interventions aimed at reducing the incidence of functional limitations in patients with oral and oropharyngeal cancer.

Diet and cancer in Northeast Brazil: evaluation of eating habits and food group consumption in relation to breast cancer

Realizou-se um estudo do tipo caso-controle de base hospitalar no Município de João Pessoa, Paraíba, Brasil. Participaram 183 indivíduos (89 casos e 94 controles) na faixa etária entre 30 e 80 anos, com pareamento por idade. O consumo alimentar de casos e controles foi avaliado por alimentos e grupos de alimentos categorizados em tercis de consumo. A estimativa dos valores da odds ratio (OR) e intervalos de confiança de 95% (IC95%) foi realizada por regressão logística múltipla não-condicional. O consumo de frutas e sucos, feijão e leite e derivados apresentou uma forte associação com a redução no risco de câncer de mama. O consumo de carnes vermelhas e de carnes fritas esteve positivamente associado ao risco de câncer de mama (carne vermelha - OR = 4.30; IC95%: 1,74-10,67; p = 0,00). Não foi observada associação entre o consumo dos grupos de vegetais e embutidos com o câncer de mama. Carne vermelha e carnes fritas podem ser fatores de risco, e o consumo de frutas, feijão e leite e derivados pode atuar como protetor do câncer de mama

Prevalence of endometrial cancer and hyperplasia in non-symptomatic overweight and obese women

Background: Obesity is a public health problem and it is necessary to identify if non-symptomatic obese women must be submitted to endometrial evaluation. Aims: To determine the prevalence of endometrial hyperplasia and cancer in non-symptomatic overweight or obese women. Methods: A cross-sectional study was carried out in 193 women submitted to an endometrial biopsy using a Pipelle de Cornier. The findings were classified as normal, hyperplasia or cancer, and the results were compared to body mass index (BMI; kg/m2). For the purpose of statistical analysis, women were divided into two groups: women of reproductive age and postmenopausal women, and according to BMI as overweight or obese. Results: The prevalence of endometrial cancer and hyperplasia was 1.0% and 5.8% in women of reproductive age and 3.0% and 12.1% in postmenopausal women, respectively. According to logistic regression, being in the postmenopause increased the risk of endometrial hyperplasia and cancer to 1.19 (95% confidence interval (CI): 0.36-3.90), while being postmenopausal and severely obese increased the odds ratio (OR) to 1.58 (95%CI: 0.30-8.23) and being postmenopausal and morbidly obese increased the OR to 2.72 (95%CI: 0.65-11.5). No increase in risk was found in women of reproductive age who were either overweight or obese. Discussion: Our results show that non-symptomatic, severe or morbidly obese postmenopausal women have a high risk of developing endometrial hyperplasia or cancer; however, no such risk was found for women of reproductive age.

Trends in socioeconomic inequalities in cancer mortality in Barcelona: 1992-2003

Background: The objective of this study was to assess trends in cancer mortality by educational level in Barcelona from 1992 to 2003. Methods: The study population comprised Barcelona inhabitants aged 20 years or older. Data on cancer deaths were supplied by the system of information on mortality. Educational level was obtained from the municipal census. Age-standardized rates by educational level were calculated. We also fitted Poisson regression models to estimate the relative index of inequality (RII) and the Slope Index of Inequalities (SII). All were calculated for each sex and period (1992-1994, 1995-1997, 1998-2000, and 2001-2003). Results: Cancer mortality was higher in men and women with lower educational level throughout the study period. Less-schooled men had higher mortality by stomach, mouth and pharynx, oesophagus, larynx and lung cancer. In women, there were educational inequalities for cervix uteri, liver and colon cancer. Inequalities of overall and specific types of cancer mortality remained stable in Barcelona; although a slight reduction was observed for some cancers. Conclusion: This study has identified those cancer types presenting the greatest inequalities between men and women in recent years and shown that in Barcelona there is a stable trend in inequalities in the burden of cancer.

Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer

Background: Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability. Methods: We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for HLA-DQA1, DRB1 and DQB1 genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis. Results: European ( E), Asian-American ( AA) and African (Af) variants were identified. Here we show that inverse association between DQB1*05 ( adjusted odds ratio [ OR] = 0.66; 95% confidence interval [CI]: 0.39-1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers ( OR = 0.27; 95% CI: 0.10-0.75). We observed similar proportions of HLA DRB1*1302 carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases ( p = 0.03, Fisher exact test). A positive association with DRB1*15 was observed in both groups of women harboring either E ( OR = 2.99; 95% CI: 1.13-7.86) or AA variants ( OR = 2.34; 95% CI: 1.00-5.46). There was an inverse association between DRB1*04 and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the E6 gene ( OR = 0.27; 95% CI: 0.08-0.96). An inverse association between DQB1*05 and cases carrying 350G (83V) variants was also found ( OR = 0.37; 95% CI: 0.15-0.89). Conclusion: Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants.

Impact of cancer-related symptom synergisms on health-related quality of life and performance status

To identify the impact of multiple symptoms and their co-occurrence on health-related quality of life (HRQOL) dimensions and performance status (PS), 115 outpatients with cancer, who were not receiving active cancer treatment and were recruited from, a university hospital in Sao Paulo, Brazil completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the Beck Depression Inventory, and the Brief Pain Inventory. Karnofsky Performance Status scores also were completed. Application of TwoStep Cluster analysis resulted in two distinct patient subgroups based on 113 patient experiences with pain, depression, fatigue, insomnia, constipation, lack of appetite, dyspnea, nausea, vomiting, and diarrhea. One group had multiple and severe symptom subgroup and another had Less symptoms and with lower severity. Multiple and severe symptoms had worse PS, role functioning, and physical, emotional, cognitive, social, and overall HRQOL. Multiple and severe symptom subgroup was also six times as likely as lower severity to have poor role functioning;five times more likely to have poor emotional;four times more likely to have poor PS, physical, and overall HRQOL, and three times as likely to have poor cognitive and social HRQOL, independent of gender, age, level of education, and economic condition. Classification and Regression Tree analyses were undertaken to identify which co-occurring symptoms would best determine reduction in HRQOL and PS. Pain and fatigue were identified as indicators of reduction on physical HRQOL and PS. Fatigue and insomnia were associated with reduction in cognitive; depression and pain in social; and fatigue and constipation in role functioning. Only depression was associated with reduction in overall HRQOL. These data demonstrate that there is a synergic effect among distinct cancer symptoms that result in reduction in HRQOL dimensions and PS.

Paclitaxel associated with cholesterol-rich nanoemulsions promotes atherosclerosis regression in the rabbit

A cholesterol-rich nanoemulsion (LDE) that resembles LDL binds to the LDL receptors and after injection into the blood stream may concentrate in cells with LDL receptor overexpression, as occurs in neoplasias and other proliferative processes. Thus, LDE can be used as vehicle to target drugs against those cells. The current study was designed to verify in rabbits whether LDE concentrates in the lesioned rabbit artery and whether a paclitaxel derivative, paclitaxel oleate, associated to LDE could reduce the atherosclerotic lesions. Sixteen male New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30 under cholesterol feeding, eight animals were treated with four weekly intravenous injections of LDE-paclitaxel (4 mg/kg) and eight with four weekly intravenous saline solution injections for additional 30 days. On day 60, the animals were sacrificed for analysis. The uptake of LDE labeled with [C-14]-cholesteryl oleate by the aortic arch of cholesterol-fed rabbits was twice as much that observed in animals fed only regular chow. LDE-paclitaxel reduced the lesion areas of cholesterol-fed animals by 60% and intima-media ratio fourfold and inhibited the macrophage migration and the smooth muscle cell proliferation and invasion of the intima. LDE-paclitaxel treatment had no toxicity. In conclusion, LDE-paclitaxel produced pronounced atherosclerosis regression without toxicity and has shown remarkable potential in cardiovascular therapeutics. (c) 2008 Published by Elsevier Ireland Ltd.

Beyond ovulation: Oral contraceptives and epithelial ovarian cancer

In a case-control study in three Australian states that included 794 women with epithelial ovarian cancer and 853 community controls for whom we had adequate contraceptive and reproductive histories, Re examined the effects of oral contraceptive use after controlling for estimated number of ovulatory cycles. Other covariates included in the multiple logistic regression analysis were parity, smoking, and history of pelvic surgery. The protective effect of duration of oral contraceptive use appeared to be multiplicative, with a 7% decrease in relative risk per year [95% confidence interval (CI) = 4-9%], persisting beyond 15 years of exposure. Use for up to 1 year may have a greater effect than predicted (odds ratio = 0.57; 95% CI = 0.40-0.82), whereas use before the first pregnancy may be additionally beneficial (odds ratio = 0.95; 95% CI = 0.87-1.03, adjusted for overall duration of use). Better control for ovulatory life might attenuate these estimates somewhat. There was little evidence of waning protection with time since last exposure or of extra benefit with early commencement of oral contraceptive use. We found no convincing evidence of effect modification in any factor examined or differences in effect among the three main histologic cancer types or between borderline and malignant tumors. Oral contraceptives may act by both suppressing ovulation and altering the tumor-promoting milieu.

Variation in cervical cancer screening by region, socio-economic, migrant and Indigenous status in women in New South Wales

The purpose of this study was to estimate the extent of association of cervical screening in NSW women with socio-economic status (SES), rurality, and proportions of non-English speaking background (NESB) and Indigenous status. Data on women who had at least one Pap test over two years (January 1998-December 1999) were obtained from the NSW Pap test Register. Each local government area (LGA) was allocated to categories of population proportions of NESB and Indigenous status, a rurality classification based on population density and remoteness, and to an SES quintile. The odds ratios (OR) of having a Pap test were estimated and confounding adjusted by multiple logistic regression analysis. Implied Pap test rates in urban NESB and in rural Indigenous women were estimated from the modelled estimates. The adjusted OR for a Pap test in large rural centres (1.14) was significantly higher than those for metropolitan or capital city residents (0.9 and 1.0 respectively). Adjusted OR for a Pap test in other rural centres (0.73) and other remote areas (0.64) were significantly lower than those for metropolitan or capital city residents. In urban populations the lowest OR were in areas with both low SES and high proportion of NESB. The lowest OR for Pap screening in rural populations occurred in the most remote areas with the highest proportion of Indigenous women. For urban NESB women the biennial Pap test rate was estimated as 50%, and for rural Indigenous women 29%, compared with the NSW average of 59%.

Long-term survival of women with breast cancer in New South Wales

Several long-term studies of breast cancer survival have shown continued excess mortality from breast cancer up to 20-40 years following treatment. The purpose of this report was to investigate temporal trends in long-term survival from breast cancer in all New South Wales (NSW) women. Breast cancer cases incident in 1972-1996 (54,228) were derived from the NSW Central Cancer Registry a population-based registry which began in 1972. All cases of breast cancer not known to be dead were matched against death records. The expected survival for NSW women was derived from published annual life tables. Relative survival analysis compared the survival of cancer cases with the age, sex and period matched mortality of the total population. Cases were considered alive at the end of 1996, except when known to be dead. Proportional hazards regression was employed to model survival on age, period and degree of spread at diagnosis. Survival at 5, 10, 15, 20 and 25 years of follow-up was 76 per cent, 65 per cent, 60 per cent, 57 per cent and 56 per cent. The annual hazard rate for excess mortality was 4.3 per cent in year 1, maximal at 6.5 per cent in year 3, declining to 4.7 per cent in year 5, 2.7 per cent in year 10, 1.4 per cent in year 15, 1.0 per cent for years 16-20, and 0.4 per cent for years 20-25 of follow-up. Relative survival was highest in 40-49 year-olds. Cases diagnosed most recently (1992-1996) had the highest survival, compared with cases diagnosed in previous periods. Five-year survival improved over time, especially from the late 1980s for women in the screening age group (50-69 years). Survival was highest for those with localised cancer at diagnosis: 88.4 per cent, 79.1 per cent, 74.6 per cent, 72.7 per cent and 72.8 per cent at 5, 10, 15, 20 and 25 years follow-up (excluding those aged greater than or equal to 70 years). There was no significant difference between the survival of the breast cancer cases and the general population at 20-25 years follow-up. Degree of spread was less predictive of survival 5-20 years after diagnosis, compared with 0-5 years after diagnosis, and was not significant at 20-25 years of follow-up. Relative survival from breast cancer in NSW women continues to decrease to 25 years after diagnosis, but there is little excess mortality after 15 years follow-up, especially for those with localised cancer at diagnosis, and the minimal excess mortality at 20-25 years of follow-up is not statistically significant. (C) 2002 Elsevier Science Ltd. All rights reserved.

Immune response to vaccination with DNA-hsp65 in a phase I clinical trial with head and neck cancer patients

DNA-hsp65, a DNA vaccine encoding the 65-kDa heat-shock protein of Mycobacterium leprae (Hsp65) is capable of inducing the reduction of established tumors in mouse models. We conducted a phase I clinical trial of DNA-hsp65 in patients with advanced head and neck carcinoma. In this article, we report on the vaccine`s potential to induce immune responses to Hsp65 and to its human homologue, Hsp60, in these patients. Twenty-one patients with unresectable squamous cell carcinoma of the head and neck received three doses of 150, 400 or 600 mu g naked DNA-hsp65 plasmid by ultrasound-guided intratumoral injection. Vaccination did not increase levels of circulating anti-hsp65 IgG or IgM antibody, or lead to detectable Hsp65-specific cell proliferation or interferon-gamma (IFN-gamma) production by blood mononuclear cells. Frequency of antigen-induced IL-10-producing cells increased after vaccination in 4 of 13 patients analyzed. Five patients showed disease stability or regression following immunization; however, we were unable to detect significant differences between these patients and those with disease progression using these parameters. There was also no increase in antibody or IFN-gamma responses to human Hsp60 in these patients. Our results suggest that although DNA-hsp65 was able to induce some degree of immunostimulation with no evidence of pathological autoimmunity, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured. Future studies should focus on characterizing more reliable correlations between immune response parameters and clinical outcome that may be used as predictors of vaccine success in immunosuppressed individuals. Cancer Gene Therapy (2009) 16, 598-608; doi:10.1038/cgt.2009.9; published online 6 February 2009

Cancer detection and mammogram volume of radiologists in a population-based screening programme

This study investigates the relationship between the number of screening mammograms read by radiologists and the screening breast cancer detection rate. Cancer detection rates for incident screens (all women aged >= 40 years) were compared by increasing categories of reader volume using Poisson regression. Data from New South Wales (NSW) for a 2 year period (2000-2001) were obtained from the BreastScreen NSW programme. Cancer detection rates increased with the number of mammograms read in the programme, reaching a plateau of approximately 40 per 10,000 after 1375 mammograms per year. No significant differences in cancer detection were evident above 875 mammograms (compared to below 875 mammograms) per year (RR = 0.79, 95% CI 0.63-0.99). (c) 2005 Elsevier Ltd. All rights reserved.

The prevalence of erectile dysfunction among Brazilian men screened for prostate cancer

OBJECTIVE To determine the prevalence of erectile dysfunction (ED) in a large cohort of Brazilian men who were screened for prostate cancer, and to determine risk factors in this population, as there are large cultural differences among countries in reporting the frequency of ED, and it is likely that the prevalence of ED among men screened for prostate cancer cannot be generally applied across countries. SUBJECTS AND METHODS The analysis focused on the baseline characteristics of 1008 consecutive South American men from Brazil with no known prostate disease who had routine screening for prostate cancer by urologists. The variables analysed were patient age, urinary symptoms, patient health-related quality of life (HRQL), prostate-specific antigen (PSA) levels, prostate volume and erectile function. To assess lower urinary tract symptoms (LUTS) and HRQL, we used the American Urological Association symptom score and its appended eighth question, respectively. Benign prostatic hyperplasia was defined as a prostate volume of > 30 g. Sexual function was assessed using the five-item version of the International Index of Erectile Function questionnaire. Thus, ED was considered to absent for scores of 22-25, mild for 17-21, mild to moderate for 12-16, moderate for 8-11, or severe for 5-7. Obesity was defined by calculating the body mass index (BMI), and categorized as underweight (< 18.5 kg/mregression models. RESULTS Information about erectile function was available for 908 patients. ED was considered to be absent, mild, mild to moderate, moderate and severe in 169 (18.6%), 210 (23.1%), 169 (18.6%), 138 (15.2%) and 222 (24.5%) patients, respectively. The ED was severe in 18.4%, 25.7% and 43.4% of patients with mild, moderate and severe LUTS, respectively (P < 0.001). The answer to the HRQL question was also significantly associated with ED; ED was severe in 16.5% of patients feeling delighted/pleased and in 35.8% of patients feeling unhappy/terrible (P < 0.001). The prostate volume was significantly related to ED. The BMI category showed that normal weight, overweight and obese patients had similar rates of ED (P = 0.415); ED was severe in about a quarter of the patients in each of these categories, and 50% and 24% of patients in the underweight and greater BMI groups had severe ED, respectively. CONCLUSIONS Of men screened for prostate cancer in Brazil, approximate to 40% have moderate or severe ED. Severe LUTS, higher HRQL scores, a large prostate volume, a low BMI and higher PSA levels might be associated with higher rates of ED. These variables should be considered when analysing the erectile function of patients screened for prostate cancer.