Interdisciplinary care programme to improve self‐management for cancer patients undergoing stem cell transplantation: a prospective non‐randomised intervention study

The purpose of this single‐centre prospective non‐randomised study was to evaluate the effectiveness of an interdisciplinary care programme to enhance self‐management in patients with haematopoietic stem cell transplantation (HSCT). Patients undergoing HSCT, aged >14 years with informed consent were recruited (n = 79). Patients in the intervention group (IG) received standard care plus the SCION‐HSCT intervention to counteract three problems after HSCT: muscle weakness, oral mucositis and malnutrition. Control group patients received standard care. Primary endpoint was global health‐related quality of life (HRQoL) at discharge (EORTC QLQ C30 v. 3.0). Baseline characteristics were balanced between both groups, except physical performance (ECOG) being significantly lower for patients of the IG. At discharge, no group differences could be seen regarding HRQoL. Non‐confirmatory post hoc analyses showed for patients of the IG a shorter duration of hospitalisation (MD ?10.90; 95% CI ?18.05 to ?3.75) and increased activity during hospitalisation (MD 2.44; 95% CI 1.27–3.61). In conclusion, clinical effectiveness of the intervention could not be proven with respect to the aspired improvement of HRQoL. However, the nurse‐led interdisciplinary caring programme could be carried out in every day ward routine. Further research should focus on working mechanisms of complex interventions aiming to improve HRQoL of patients undergoing HSCT.     

Insulin resistance, central obesity, and risk of colorectal adenomas

BACKGROUND:

Increasing evidence supports insulin resistance (IR) as the underpinning of the obesity‐colorectal neoplasia link. The homeostasis model assessment‐IR (HOMA‐IR) is a widely accepted index of evolving hyperinsulinemia and early IR. Studies of the relation between HOMA‐IR and colorectal adenomas are limited. Therefore, the authors sought to determine the associations of HOMA‐IR and central obesity (waist to hip ratio [WHR]) with risk of colorectal adenomas in a screening colonoscopy‐based study.

METHODS:

The authors collected lifestyle information and fasting blood samples from 1222 participants (320 incident adenoma cases and 902 without adenomas) before their screening colonoscopies. Unconditional logistic regression models were used to assess risk associations.

RESULTS:

In multivariate analysis of participants (n = 1093) reporting no antidiabetic medication use, those in the top quartile of WHR were twice as likely (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.33‐3.57; P‐trend = .003) and those in the top quartile of HOMA‐IR were 63% more likely (OR, 1.63; 95% CI, 1.09‐2.44; P‐trend = .01) to have adenomas compared with those in the bottom quartiles. Stratified analysis revealed a statistically significant interaction between HOMA‐IR and sex (P‐interaction = .04), with the association largely limited to men; compared with those in the bottom tertile, men in the top tertile of HOMA‐IR were twice more likely to have adenomas (OR, 2.11; 95% CI, 1.18‐3.78; P‐trend = .01).

CONCLUSIONS:

The results support central obesity and insulin resistance, particularly in men, as important risk factors for the development of early colorectal neoplasia. Cancer 2012;. © 2011 American Cancer Society.     

Plasma insulin,C‐peptide and blood glucose and the risk of gastric cancer: The Japan Public Health Center‐based prospective study

To date, the association between diabetes mellitus (DM) and gastric cancer has been controversial, including the underlying mechanism. We investigated the association between plasma diabetic biomarkers (insulin, C‐peptide, and blood glucose) and gastric cancer risk. In addition, homeostasis model assessment of insulin resistance (HOMA‐IR) and homeostasis model assessment of β‐cell function (HOMA‐β) were calculated. A total of 36,745 subjects aged 40–69 years in the Japan Public Health Center‐based prospective study (JPHC) who returned the baseline questionnaire and provided blood samples were followed from 1990 to 2004. In the present analysis, 477 cases and 477 matched controls were used. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for developing gastric cancer were calculated using conditional logistic regression models. Plasma insulin was positively associated with increased risk of gastric cancer; compared to tertile 1, ORs were 1.69 (95% CI = 1.11–2.59) and 2.01 (1.19–3.38) for tertiles 2 and 3, respectively (p for trend = 0.009). In men, C‐peptide was also positively associated with a significant risk; corresponding ORs were 1.42 (0.85–2.38) and 1.91 (1.03–3.54), respectively (p for trend = 0.04). These findings were confirmed for blood samples from the fasting group (≥8 hr after a meal). Higher HOMA‐IR was also associated with increased risk, whereas no association was observed for blood glucose. Our findings suggest that Japanese population with higher insulin and C‐peptide levels derived from insulin resistance have an elevated risk of gastric cancer.     

Efficacy of a global supportive skin care programme with hydrotherapy after non‐metastatic breast cancer treatment: A randomised,controlled study

This study investigated the efficacy of post‐treatment hydrotherapy as supportive care for management of persistent/long‐lasting dermatologic adverse events (dAEs) induced in breast cancer survivors by adjuvant therapy, and its impact on quality of life (QoL). Patients in complete remission after standardised (neo)adjuvant chemotherapy, surgery and radiotherapy combination treatment for infiltrating HR+/HER2‐breast carcinoma were enrolled in this randomised, multicentre controlled study 1–5 weeks after completing radiotherapy. The control group (CG, n = 33) received best supportive care and the treatment group (HG, n = 35) received 3‐weeks of specific hydrotherapy. The primary criterion was change in QoL (QLQ‐BR23) after hydrotherapy. Clinical grading of dAEs, cancer‐related QoL (QLQ‐C30), dermatologic QoL (DLQI) and general psychological well‐being (PGWBI) were assessed. Significant dAEs were found at inclusion in both groups (n = 261). Most items showed significantly greater improvement in the HG versus CG group: QLQ‐BR23 (breast [p = .0001] and arm symptoms [p = .0015], systemic therapy side effects [p = .0044], body image [p = .0139]), some dAE grading, DLQI (p = .0002) and PGWBI (p = .0028). Xerosis (88% of patients at inclusion) completely healed in all HG patients. Specific hydrotherapy is an effective supportive care for highly prevalent and long‐lasting dAEs occurring after early breast cancer treatment, including chemotherapy, and leads to improved QoL and dermatologic toxicities.     

Changes in metabolic risk,insulin resistance,leptin and adiponectin following a lifestyle intervention in overweight and obese breast cancer survivors

Adiposity and physical activity are modifiable factors that could be important determinants of breast cancer (BC) prognosis through their effects on endogenous reproductive hormones, chronic inflammation and metabolic changes. Therefore, it is necessary to evaluate whether offering lifestyle interventions to BC survivors could affect the levels of certain biomarkers involved in these mechanisms. We designed a pre–post intervention study offering diet and exercise sessions over 12 weeks to 42 overweight/obese BC survivors. Before and after the intervention, we obtained dietary information, anthropometry and cardiorespiratory fitness (CRF) measurements and blood samples to measure metabolic risk, insulin resistance and adipokines biomarkers. Wilcoxon signed‐rank tests and Spearman partial correlation coefficients were used to compare pre‐ and post‐measurements and assess the correlations between changes in biomarkers and changes in anthropometry and CRF. Breast cancer survivors showed significant improvements in metabolic risk biomarkers and insulin resistance indicators along with a non‐significant leptin decrease and a significant adiponectin decrease. The improvements in metabolic risk biomarkers, insulin resistance indicators and leptin were moderately correlated (0.32 ≤ |r| ≤ 0.55) with the decrease in body mass index and the increase in CRF. Diet and exercise interventions implemented in overweight/obese BC survivors may improve metabolic risk, insulin resistance and leptin biomarkers.     

Unmet supportive care needs,health status and minimum costs in survivors of malignant melanoma

We explored the relationship between unmet care needs, health status, health utility and costs in people treated for melanoma via a cross‐sectional follow‐up survey (N = 455) 3 months to 5 years after complete resection of stage I–III cutaneous malignant melanoma. 51% (n = 232) had unmet care needs. This group had higher mean resource use, estimated conservatively (£28 vs. £10 per person) and worse overall health. Mean health‐related utility index (AQoL6D) was 0.763 (95% CI 0.74; 0.79) in those with self‐reported unmet need vs. 0.903 (0.89; 0.92) in those with no unmet need. Melanoma survivors with unmet need had worse outcomes in terms of anxiety (HADS 6.86 vs. 4.29), depression (HADS 4.29 vs. 2.01), overall quality of life (QoL: FACT‐M 84.2 vs. 96.5). Higher resource use was associated with younger age (r_s = ?.29, p < .001), older school‐leaving age (r_s = .21, p < .001), reduced health utility (r_s = ?.14, p = .005), higher anxiety (r_s = .22, p < .001), higher depression (r_s = .16, p = .001) and lower QoL (overall r_s = ?.24, p < .001; melanoma QoL r_s = ?.20, p < .001; surgery QoL r_s = ?.19, p < .001). Lower health outcomes indicate increased service use, suggesting that interventions to address unmet need and improve health outcomes may reduce health costs. Integrated clinical and economic evaluations of interventions that target unmet need in melanoma survivors are required.     

Chronic nonsteroidal anti-inflammatory drug (NSAID) use suppresses multiple CpG islands hyper methylation (CIHM) of tumor suppressor genes in the human gastric mucosa

There have been reports showing a protective role of nonsteroidal anti‐inflammatory drugs (NSAIDs) against gastrointestinal cancers. CpG island hyper methylation (CIHM) of tumor suppressor genes is a major event in carcinogenesis. We investigated the CIHM status of non‐cancerous gastric mucosa in chronic NSAID users and non‐users and assessed the effect of NSAIDs on CIHM. Gastric mucosa samples were obtained from 51 chronic NSAID users and 180 non‐users. CIHM of p14(ARF), p16(INK4a), death‐associated protein kinase (DAP‐kinase), and E‐cadherin (CDH1) genes were determined by methylation‐specific PCR. CIHM high was defined as two or more CpG islands methylated. CIHM of p14, p16, CDH1, and CIHM high were lower in chronic NSAID users than in non‐users (p14: non‐users vs users = 32.2%vs 9.8%, P = 0.003; p16: non‐users vs users = 35.0%vs 15.7%, P = 0.02; CDH1: non‐users vs users = 36.1%vs 9.8%, P = 0.0009; CIHM high: non‐users vs users = 44.4%vs 17.6%, P = 0.0009). NSAID use was also associated with decreased number of CIHM by anova (R = –0.32, P < 0.0001). Multivariate logistic regression analysis with adjustment for sex, age, Helicobacter pylori infection, and NSAID use revealed that NSAID use was inversely correlated with all four CIHM and CIHM high as an independent factor (p14: odds ratio [OR] = 0.17, 95% confidence interval [CI] = 0.06–0.48; p16: OR = 0.32, 95% CI = 0.14–0.75; DAP‐kinase: OR = 0.45, 95% CI = 0.22–0.92; CDH1: OR = 0.18, 95% CI = 0.06–0.48; CIHM high: OR = 0.21, 95% CI = 0.09–0.49). No association was found between CIHM status and the duration or dose of NSAIDs. Chronic NSAID use suppresses CIHM in human gastric mucosa. NSAIDs may have a suppressive role against methylation‐related gastric carcinogenesis. (Cancer Sci 2009; 100: 1192–1197)     

Metabolic obesity phenotypes and risk of colorectal cancer in postmenopausal women

Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model‐insulin resistance (HOMA‐IR—a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross‐classified by BMI (18.5–<25.0, 25.0–<30.0 and ≥30.0 kg/m²) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA‐IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis.     

Dual tumor‐suppressors miR‐139‐5p and miR‐139‐3p targeting matrix metalloprotease 11 in bladder cancer

Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep‐sequencing revealed that two miRNA, microRNA‐139‐5p/microRNA‐139‐3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature miRNA or small interfering RNA (siRNA). Genome‐wide gene expression analysis, in silico analysis and dual‐luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan–Meier method. Gain‐of‐function studies showed that miR‐139‐5p and miR‐139‐3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR‐139‐5p and miR‐139‐3p. Kaplan–Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR‐139‐5p or miR‐139‐3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNA and might be a good prognostic marker for survival of BC patients.     

Effectiveness of telephone‐based interventions on health‐related quality of life and prognostic outcomes in breast cancer patients and survivors—A meta‐analysis

The aim of this meta‐analysis was to evaluate the effect of telephone‐based interventions on prognostic outcomes and health‐related quality of life (HRQoL) in breast cancer patients and survivors. A systematic search of the Cochrane Library, Web of science, Medline, EMBASE, CNKI and CBM database was carried out. Randomised, controlled trials (RCTs) examining the effects of telephone‐based intervention versus a control group receiving no telephone intervention, on prognostic outcomes and HRQoL with breast cancer were included. A meta‐analysis was conducted to quantify the effects of telephone‐based interventions on anxiety, depression, fatigue, self‐efficiency, physiological function, social‐domestic function and quality of life. In total, 14 studies involving 2002 participants were included. Due to the effect of telephone‐based interventions, statistically significant results were found on anxiety (standard mean difference [SMD] = ?0.16, 95% confidence intervals [CI] [0.01, 0.30], p = .04), self‐efficiency (SMD = 0.22, 95% CI [?0.34, ?0.10], p = .0004), social‐domestic function (SMD = 0.19, 95% CI [?0.35, ?0.03], p = .02) and quality of life (SMD = 0.54, 95% CI [?1.00, ?0.08], p = .02). Although the effects on depression, fatigue and physiological function were in the expected direction, these effects were not statistically significant (p > .05) based on the insufficient evidence.     

Obesity induced a leptin‐Notch signaling axis in breast cancer

To investigate whether obesity induces a leptin‐Notch signaling axis in breast cancer (BC), leptin‐induced Notch was determined in human MCF‐7 and MDA‐MB231 and mouse E0771 cells and in E0771‐BC hosted by syngeneic lean and diet‐induced obesity (DIO) C57BL/6J female mice. Lean and DIO mice were treated for 3 weeks with leptin inhibitor (PEG‐LPrA2) 1 week after the inoculation of E0771 cells. Leptin induced Notch1, 3 and 4 in BC cells, but Notch2 expression showed opposite pattern in MCF‐7 compared to MDA‐MB231 cells. Notch loss‐of‐function (DAPT and dominant negative [R218H] RBP‐Jk [CSL/CBF1]) showed that a functional leptin‐Notch signaling axis was involved in the proliferation and migration of E0771 cells. E0771‐BC onset was affected by obesity (lean mice7/10 [70%] vs. DIO mice: 11/12 [92%]; Pearson χ²: p = 0.06]). PEG‐LPrA2 significantly reduced BC growth (untreated: 19/42; [45%] vs. treated: 8/42 [19%]; Pearson χ²: p = 0.008). PEG‐LPrA2 did not influence the caloric intake of mice but increased carcass and/or body weights of lean and DIO mice inoculated with E0771 cells, which could be related to the improvement of health conditions (less aggressive disease). Importantly, BC from obese mice had higher levels of Notch3, JAG1 and survivin than lean mice. Inhibition of leptin signaling reduced protein levels of Notch (NICD1, NICD4, Notch3, JAG1 and survivin) and significantly decreased mRNA expression of Notch receptors, ligands and targets. PEG‐LPrA's effects were more prominent in DIO mice. Present data suggest that leptin induces Notch, which could be involved in the reported higher incidence and aggressiveness and, poor prognosis of BC in obese patients.     

Prediagnostic plasma IGFBP‐1, IGF‐1 and risk of prostate cancer

Insulin‐like growth factor (IGF)?1 is associated with a higher risk of prostate cancer. IGF‐binding protein (IGFBP)?1, a marker for insulin activity, also binds IGF‐1 and inhibits its action. Data on IGFBP‐1 and prostate cancer risk are sparse and whether the IGF and insulin axes interact to affect prostate cancer carcinogenesis is unknown. We evaluated the independent and joint influence of prediagnostic plasma levels of IGFBP‐1 (fasting) and IGF‐1 on risk of prostate cancer among 957 cases and 1,021 controls with fasting levels of IGFBP‐1 and 1,709 cases and 1,778 controls with IGF‐1 nested within the Health Professionals Follow‐up Study. Unconditional logistic regression adjusting for matching factors was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Higher prediagnostic fasting IGFBP‐1 levels were associated with lower risk of prostate cancer (highest vs. lowest quartile OR = 0.67, 95% CI 0.52–0.86, p_trend = 0.003), which remained similar after adjusting for IGF‐1. Prediagnostic IGF‐1 was associated with increased risk of prostate cancer (highest vs. lowest quartile OR = 1.28, 95% CI = 1.05–1.56, p_trend = 0.01). The associations with each marker were primarily driven by lower‐grade and non‐advanced prostate cancer. Being low in IGFBP‐1 and high in IGF‐1 did not confer appreciable additional risk (p_interaction = 0.42). In summary, prediagnostic fasting IGFBP‐1 may influence prostate cancer carcinogenesis. Being low in IGFBP‐1 or high in IGF‐1 is sufficient to elevate the risk of prostate cancer.     

Contralateral risk-reducing mastectomy in <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> mutation carriers and other high-risk women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)

The purpose of this study is to determine the prevalence and predictors of contralateral risk-reducing mastectomy (CRRM) in Australasian women at high familial risk of a second primary breast cancer (BC). Participants were women with unilateral BC and a strong family history of the disease, including BRCA1/2 mutation carriers. Data were collected through interview, self-administered questionnaire and review of pathology and surgical reports. Associations between CRRM and potential predictors were assessed using multivariate logistic regression. Of 1,018 women (median follow-up 11.1 years), 154 (15%) underwent CRRM, 43% of these within 12 months of initial BC surgery. More likely to undergo CRRM were women who were younger at BC diagnosis (odds ratio [OR] = 0.94 per year of age, P < 0.001), were diagnosed more recently (OR = 1.16 per calendar year, P < 0.001), underwent mastectomy as initial definitive BC treatment (OR = 5.2, P < 0.001) and underwent risk-reducing salpingo-oophorectomy (OR = 3.4, P < 0.001). BRCA1/2 mutation status, axillary nodal status and receipt of chemotherapy were not independently associated with CRRM uptake. A contralateral BC event (invasive or in situ) occurred in 177 (20.5%) of the 864 women who did not have CRRM, compared with one chest wall event (0.6%) in the 154 women post-CRRM. The contralateral event rate was 15.1 per 1,000 women-years for non-CRRM women and 0.7 per 1,000 women-years for CRRM women; P < 0.0001. Younger women with more recently diagnosed BC treated with mastectomy are more likely to elect CRRM. Neither BRCA1/2 mutation status, nor the competing risk of BC recurrence and death, appears to influence decision making.     

DNA methylation array analyses identified breast cancer‐associated HYAL2 methylation in peripheral blood

Breast cancer (BC) is the leading cause of cancer‐related mortality in women worldwide. Changes in DNA methylation in peripheral blood could be associated with malignancy at early stage. However, the BC‐associated DNA methylation signatures in peripheral blood were largely unknown. Here, we performed a genome‐wide methylation screening and identified a BC‐associated differentially methylated CpG site cg27091787 in the hyaluronoglucosaminidase 2 gene (HYAL2) (discovery round with 72 BC case and 24 controls: p = 2.61 × 10^?9 adjusted for cell‐type proportions). The substantially decreased methylation of cg27091787 in BC cases was confirmed in two validation rounds (first validation round with 338 BC case and 507 controls: p < 0.0001; second validation round with 189 BC case and 189 controls: p < 0.0001). In addition to cg27091787, the decreased methylation of a 650‐bp CpG island shore of HYAL2 was also associated with increased risk of BC. Moreover, the expression and methylation of HYAL2 were inversely correlated with a p‐value of 0.006. To note, the BC‐associated decreased HYAL2 methylation was replicated in the T‐cell fraction (p = 0.034). The cg27091787 methylation level enabled a powerful discrimination of early‐stage BC cases (stages 0 and I) from healthy controls [area under curve (AUC) = 0.89], and was robust for the detection of BC in younger women as well (age < 50, AUC = 0.87). Our study reveals a strong association between decreased HYAL2 methylation in peripheral blood and BC, and provides a promising blood‐based marker for the detection of early BC.     

Impact of body mass index and visceral adiposity on outcomes in colorectal cancer

Aim: Obesity and visceral obesity are closely related to the development of colorectal cancer, as well as other metabolic complications. We investigated the prognostic significance of body mass index (BMI) and visceral obesity in 273 patients with resectable colorectal cancer. Methods: Visceral fat area (VFA) and subcutaneous fat area were measured on digital images of patients’ computed tomograms obtained before surgery. The patients were divided into two groups according to the cut‐off levels of VFA proposed by Oka et al. Men with a VFA of ≥130 cm² and women with a VFA of ≥90 cm² were classified as obese (VFA‐obese) and the others were classified as non‐obese (VFA‐non‐obese). The patients were also divided into an overweight group and a normal range group, according to their preoperative BMI. Results: There was no significant difference in cumulative recurrence‐free survival (RFS) or overall survival (OS) between the VFA‐obese group and the VFA‐non‐obese group. In the subgroup of patients with Dukes’ C disease (n = 100) there was no statistically significant difference in RFS and OS between the VFA‐obese group and the VFA‐non‐obese group. The results were similar when the patients were classified according to their BMI. Conclusion: Neither obesity nor increased visceral adiposity has any influence on outcomes in patients with resectable colorectal cancer.     

Longitudinal associations of blood markers of insulin and glucose metabolism and cancer mortality in the third National Health and Nutrition Examination Survey

Insulin and glucose may influence cancer mortality via their proliferative and anti-apoptotic properties. Using longitudinal data from the nationally representative Third National Health and Nutrition Examination Survey (NHANES III; 1988–1994), with an average follow-up of 8.5 years to death, we evaluated markers of glucose and insulin metabolism, with cancer mortality, ascertained using death certificates or the National Death Index. Plasma glucose, insulin, C-peptide, and lipid concentrations were measured. Anthropometrics, lifestyle, medical, and demographic information was obtained during in-person interviews. After adjusting for age, race, sex, smoking status, physical activity, and body mass index, for every 50 mg/dl increase in plasma glucose, there was a 22% increased risk of overall cancer mortality. Insulin resistance was associated with a 41% (95% confidence interval (CI) (1.07–1.87; p = 0.01) increased risk of overall cancer mortality. These associations were stronger after excluding lung cancer deaths for insulin-resistant individuals (HR: 1.67; 95% CI: 1.15–2.42; p = 0.01), specifically among those with lower levels of physical activity (HR: 2.06; 95% CI: 1.4–3.0; p = 0.0001). Similar associations were observed for other blood markers of glucose and insulin, albeit not statistically significant. In conclusion, hyperglycemia and insulin resistance may be ‘high-risk’ conditions for cancer mortality. Managing these conditions may be effective cancer control tools.     

Dietary supplementation with branched‐chain amino acids suppresses diethylnitrosamine‐induced liver tumorigenesis in obese and diabetic C57BL/KsJ‐db/db mice

Obesity and related metabolic abnormalities, including insulin resistance, are risk factors for hepatocellular carcinoma in non‐alcoholic steatohepatitis as well as in chronic viral hepatitis. Branched‐chain amino acids (BCAA), which improve insulin resistance, inhibited obesity‐related colon carcinogenesis in a rodent model, and also reduced the incidence of hepatocellular carcinoma in obese patients with liver cirrhosis. In the present study, we determined the effects of BCAA on the development of diethylnitrosamine (DEN)‐induced liver tumorigenesis in obese C57BL/KsJ‐db/db (db/db) mice with diabetes mellitus. Male db/db mice were given tap water containing 40 ppm DEN for an initial 2 weeks and thereafter they received a basal diet containing 3.0% of BCAA or casein, which served as a nitrogen content‐matched control of BCAA, throughout the experiment. Supplementation with BCAA significantly reduced the total number of foci of cellular alteration, a premalignant lesion of the liver, and the expression of insulin‐like growth factor (IGF)‐1, IGF‐2, and IGF‐1 receptor in the liver when compared to the casein supplementation. BCAA supplementation for 34 weeks also significantly inhibited both the development of hepatocellular neoplasms and the proliferation of hepatocytes in comparison to the basal diet or casein‐fed groups. Supplementation with BCAA improved liver steatosis and fibrosis and inhibited the expression of α‐smooth muscle actin in the DEN‐treated db/db mice. The serum levels of glucose and leptin decreased by dietary BCAA, whereas the value of the quantitative insulin sensitivity check index increased by this agent, indicating the improvement of insulin resistance and hyperleptinemia. In conclusion, oral BCAA supplementation improves insulin resistance and prevents the development of liver tumorigenesis in obese and diabetic mice. (Cancer Sci 2009)     

Physical activity and mammographic breast density in a Mediterranean population: The EPIC Florence longitudinal study

A protective effect of physical activity (PA) on breast cancer (BC) risk has been suggested. Few studies have examined the influence of PA on mammographic breast density (MBD), a strong risk factor for BC. In a prospective study in Florence, Italy, we identified 2,000 healthy women with a mammogram taken 5 years after enrolment. Individual mammograms were retrieved (83%) and MBD assessed according to Wolfe's classification. Detailed information on PA at work and during leisure time, reproductive history, lifestyle and anthropometric measurements at enrolment were available for 1,666 women. Information on hormone replacement therapy (HRT) was also obtained at mammogram. Women with high‐MBD (P2 + DY Wolfe's patterns) were compared with women with low‐MBD (N1 + P1) by multivariate logistic models. Overall, high‐MBD was inversely associated with increasing levels of leisure time PA (p for trend = 0.04) and among peri‐/postmenopausal women, also with increasing levels of recreational activities (p for trend = 0.02). An interaction between PA and HRT emerged, with a stronger inverse association of highest level of recreational activity with MBD among HRT nonusers (p for interaction = 0.02). A modifying effect by body mass index (BMI) was evident among 1,025 peri‐/postmenopausal women who did not use HRT at the time of mammogram, with a stronger inverse association between recreational PA and MBD in the highest BMI tertile (OR = 0.34; 95% CI 0.20–0.57; p for interaction = 0.03). This large study carried out in Mediterranean women suggests that leisure time PA may play a role in modulating MBD, particularly in overweight/obese peri‐/postmenopausal women. © 2008 Wiley‐Liss, Inc.     

Factors associated with intentional and unintentional non‐adherence to adjuvant endocrine therapy following breast cancer

Adherence to adjuvant endocrine therapy (AET) following breast cancer is known to be suboptimal despite its known efficacy in reducing recurrence and mortality. This study aims to investigate factors associated with non‐adherence and inform the development of interventions to support women and promote adherence. A questionnaire survey to measure level of adherence, side effects experienced, beliefs about medicine, support received and socio‐demographic details was sent to 292 women 2–4 years post breast cancer diagnosis. Differences between non‐adherers and adherers to AET were explored, and factors associated with intentional and unintentional non‐adherence are reported. Approximately one quarter of respondents, 46 (22%), were non‐adherers, comprising 29 (14%) intentional non‐adherers and 17 (8%) unintentional non‐adherers. Factors significantly associated with intentional non‐adherence were the presence of side effects (p < .03), greater concerns about AET (p < .001) and a lower perceived necessity to take AET (p < .001). Half of the sample (105/211) reported that side effects had a moderate or high impact on their quality of life. Factors associated with unintentional non‐adherence were younger age (<65) (p < .001), post‐secondary education (p = .046) and paid employment (p = .031). There are distinct differences between intentional non‐adherence and unintentional non‐adherence. Differentiation between the two types of non‐adherence may help tailor support and advice interventions.     

Development of health‐related quality of life and symptoms in patients with advanced cancer in Greenland

A prospective national cohort study assessed the development of health‐related quality of life (HRQoL) and symptoms in adult patients undergoing treatment and care for advanced cancer in Greenland. HRQol was examined by EORTC QLQ‐C30 version 3.0 questionnaire monthly for 4 months. Changes over time and between‐group comparisons were examined. Of 58 patients included in the study, 47% completed the questionnaire four times. Functioning was generally high, and improved social functioning was observed after 1 and 2 months. The highest symptom score was for fatigue followed by pain and nausea/vomiting. A high score for financial problems remained unchanged during the entire period. Patients with higher income had reduced pain intensity (p = .03) and diarrhoea (p = .05) than patients with income below the poverty line. After 1 month, reduction in pain intensity was observed for Nuuk citizens compared with non‐Nuuk citizens (p = .05). After 2 months, non‐Nuuk citizens reported improved social functioning compared with Nuuk citizens (p = .05). After 3 months, Global Health in Nuuk citizens was improved compared with non‐Nuuk citizens (p = .05). An important clinical finding was that patients’ needs for support are related to social status, and geographical factors should be taken into account when planning palliative care.