Investigating reasons for socioeconomic inequalities in breast cancer survival in New Zealand

Background: This study investigated the role that demographic and tumour factors play in explaining socioeconomic inequalities in breast cancer survival. Methods: Breast cancer cases notified to the New Zealand Cancer Registry (NZCR) from April 2005 to April 2007 were followed up to April 2009. The New Zealand area-based deprivation index (NZDep) was used as a measure of socioeconomic position. Relative survival rates were estimated using sex-, deprivation- and ethnic-specific life tables. Multiple imputation was used to impute missing data. Excess mortality modelling was used to estimate the contribution of demographic and tumour factors to inequalities in survival. Results: There were 2968 breast cancer cases included and 433 recorded deaths. Relative survival rates at 4 years varied across deprivation groups. Using NZDep deciles 1–4 (least deprived) as the reference group, the age- and ethnicity-adjusted hazard ratio (HR) for NZDep deciles 7–8 was 2.03 (CI 1.36–3.04) and for NZDep deciles 9–10 was 1.93 (CI 1.28–2.92). In the fully adjusted model there remained 50% excess mortality for the two most deprived groups compared to the most affluent. Variables which measured timely access to care (extent/size) accounted for more of the survival disparity than breast cancer subtype variables (ER/PR/HER2). Conclusion: Women from deprived areas in New Zealand who are diagnosed with breast cancer are less likely to survive as long as those from affluent areas. A substantial proportion of these socioeconomic disparities can be attributed to differential access to health care although other factors, currently unknown, are also likely to play an important role.     

Relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer.

OBJECTIVE--To investigate the relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer as a possible explanation for socioeconomic differences in survival. DESIGN--Retrospective analysis of data from cancer registry and from pathology and biochemistry records. SETTING--Catchment areas of two large teaching hospitals in Glasgow. SUBJECTS--1361 women aged under 75 who had breast cancer diagnosed between 1980 and 1987. MAIN OUTCOME MEASURES--Tumour size, axillary lymph node status, histological grade, and oestrogen receptor concentration in relation to deprivation category of area of residence. RESULTS--There was no significant relation between socioeconomic deprivation and four pathological prognostic factors: 93 (32%) women in the most affluent group presented with tumours less than 20 mm in size compared with 91 (31%) women in the most deprived group; 152 (48%) of the most affluent group presented with negative nodes compared with 129 (46%) of the most deprived group; 23 (22%) of the most affluent group presented with grade I tumours compared with 12 (17%) of the most deprived group; and 142 (51%) of the most affluent group had a low oestrogen receptor concentration at presentation compared with 148 (52%) of the most deprived group. None of these differences was statistically significant. CONCLUSIONS--Differences in survival from breast cancer by socioeconomic deprivation category could not be accounted for by differences in tumour stage or biology. Other possible explanations, such as differences in treatment or in host response, should be investigated.     

Linking of Primary Care Records to Census Data to Study the Association between Socioeconomic Status and Cancer Incidence in Southern Europe: A Nation-Wide Ecological Study

Background

Area-based measures of economic deprivation are seldom applied to large medical records databases to establish population-scale associations between deprivation and disease.

Objective

To study the association between deprivation and incidence of common cancer types in a Southern European region.

Methods

Retrospective ecological study using the SIDIAP (Information System for the Development of Research in Primary Care) database of longitudinal electronic medical records for a representative population of Catalonia (Spain) and the MEDEA index based on urban socioeconomic indicators in the Spanish census. Study outcomes were incident cervical, breast, colorectal, prostate, and lung cancer in 2009–2012. The completeness of SIDIAP cancer recording was evaluated through linkage of a geographic data subset to a hospital cancer registry. Associations between MEDEA quintiles and cancer incidence was evaluated using zero-inflated Poisson regression adjusted for sex, age, smoking, alcoholism, obesity, hypertension, and diabetes.

Results

SIDIAP sensitivity was 63% to 92% for the five cancers studied. There was direct association between deprivation and lung, colorectal, and cervical cancer: incidence rate ratios (IRR) 1.82 [1.64–2.01], IRR 1.60 [1.34–1.90], IRR 1.22 [1.07–1.38], respectively, comparing the most deprived to most affluent areas. In wealthy areas, prostate and breast cancers were more common: IRR 0.92 [0.80–1.00], IRR 0.91 [0.78–1.06]. Adjustment for confounders attenuated the association with lung cancer risk (fully adjusted IRR 1.16 [1.08–1.25]), reversed the direction of the association with colorectal cancer (IRR 0.90 [0.84–0.95]), and did not modify the associations with cervical (IRR 1.27 [1.11–1.45]), prostate (0.74 [0.69–0.80]), and breast (0.76 [0.71–0.81]) cancer.

Conclusions

Deprivation is associated differently with the occurrence of various cancer types. These results provide evidence that MEDEA is a useful, area-based deprivation index for analyses of the SIDIAP database. This information will be useful to improve screening programs, cancer prevention and management strategies, to reach patients more effectively, particularly in deprived urban areas.     

Deprivation and mortality in Scotland, 1981 and 1991.

OBJECTIVE--To compare the mortality experience of Scottish postcode sectors characterised by socioeconomic census variables (Carstairs scores) in 1980-2 and 1990-2. METHODS--Variables derived from the 1981 and 1991 censuses were combined according to the method devised by Carstairs and Morris to obtain Carstairs scores for 1010 postcode sectors in Scotland in 1981 and 1001 sectors in 1991. For most analyses, these scores were grouped into seven deprivation categories ranging from affluent (category 1) to deprived (category 7) localities. MAIN OUTCOME MEASURES--Death rates and standardised mortality ratios for localities according to deprivation category. RESULTS--Postcode sectors in Scotland that were categorised as deprived in 1981 were relatively more deprived at the time of the 1991 census; the mortality experience of deprived localities relative to either Scotland or affluent neighbourhoods worsened over this period, with a 162% difference between the most affluent and most deprived categories in 1991-2. Although the age and sex standardised mortality for ages 0-64 in Scotland declined by 22% during the 1980s, the reduction in the deprived categories was only about half that of the affluent groups. Increases in the death rate for men (29%) and women (11%) aged 20-29 in the deprived groups were largely attributable to an increase in the rates of suicide. Death rates from ischaemic heart disease and carcinoma of the lung and bronchus at ages 40-69 were lower in all deprivation categories in 1990-2, but the reduction was greater in more affluent areas; the difference in rates for these conditions between affluent and deprived groups therefore increased over the decade. The observed worsening of the standardised mortality ratio for Glasgow relative to Scotland could be explained on the basis of these mortality differentials and the concentration of deprived postcode sectors in Glasgow. CONCLUSIONS--Differences in mortality experience linked to relative poverty increased in the 10 years between 1981 and 1991 censuses. Although mortality for Scotland as a whole is improving, the picture is one of an increasing distinction between the experience of the majority and that of a substantial minority of the population.     

The relationship between ethnicity,social deprivation and late presentation of colorectal cancer

IntroductionTumour staging at time of presentation is an important factor in determining survival in colorectal cancer. The aim of this paper is to investigate the relationship between ethnicity and deprivation in late (Stage IV) presentation of colorectal cancer.MethodsData from the Thames Cancer Registry comprising 77,057 colorectal cancer patients between the years 2000 and 2012 were analysed.ResultsA total of 17,348 patients were identified with complete data, of which 53.9% were male. Patients from a Black Afro/Caribbean background were diagnosed with CRC at a much younger age than the White British group (median age 67 compared with 72, p < 0.001). In multiple regression, ethnicity, deprivation and age were positive predictors of presenting with advanced tumour stage at time of diagnosis. Black patients were more likely to present with Stage IV tumours than white patients (OR 1.37, 95% CI 1.18–1.59, p < 0.001). Social deprivation was also a predictor of Stage IV cancer presentation, with the most deprived group (Quintile 5) 1.26 times more likely to be diagnosed with Stage IV cancer compared with the most affluent group (CI 1.13–1.40, p < 0.001). Sub-group analyses demonstrated that Black & Affluent patients were still at greater risk of Stage IV CRC than their White & Affluent counterparts (OR 1.24, 95% CI 1.11–1.45, p = 0.023). Patients with rectal cancer were less likely to present with Stage IV CRC (OR 0.66, 95% CI 0.61–0.71, p < 0.001).ConclusionRacial and age related disparities exist in tumour presentation in the United Kingdom. Patients from black and socially deprived backgrounds as well as the elderly are more likely to present with advanced tumours at time of diagnosis.     

Do interventions that improve immunisation uptake also reduce social inequalities in uptake?

OBJECTIVE--To investigate whether an intervention designed to improve overall immunisation uptake affected social inequalities in uptake. DESIGN--Cross-sectional small area analyses measuring immunisation uptake in cohorts of children before and after intervention. Small areas classified into five groups, from most deprived to most affluent, with Townsend deprivation score of census enumeration districts. SETTING--County of Northumberland. SUBJECTS--All children born in country in four birth cohorts (1981-2, 1985-6, 1987-8, and 1990-1) and still resident at time of analysis. MAIN OUTCOME MEASURES--Overall uptake in each cohort of pertussis, diphtheria, and measles immunisation, difference in uptake between most deprived and most affluent areas, and odds ratio of uptake between deprived and affluent areas. RESULTS--Coverage for pertussis immunisation rose from 53.4% in first cohort to 91.1% in final cohort. Coverage in the most deprived areas was lower than in the most affluent areas by 4.7%, 8.7%, 10.2%, and 7.0% respectively in successive cohorts, corresponding to an increase in odds ratio of uptake between deprived and affluent areas from 1.2 to 1.6 to 1.9 to 2.3. Coverage for diphtheria immunisation rose from 70.0% to 93.8%; differences between deprived and affluent areas changed from 8.6% to 8.3% to 9.0% to 5.5%, corresponding to odds ratios of 1.5, 2.0, 2.5, and 2.6. Coverage for measles immunisation rose from 52.5% to 91.4%; differences between deprived and affluent areas changed from 9.1% to 5.7% to 8.2% to 3.6%, corresponding to odds ratios of 1.4, 1.4, 1.7, and 1.5. CONCLUSION--Despite substantial increase in immunisation uptake, inequalities between deprived and affluent areas persisted or became wider. Any reduction in inequality occurred only after uptake in affluent areas approached 95%. Interventions that improve overall uptake of preventive measures are unlikely to reduce social inequalities in uptake.     

The breast cancer paradox: A systematic review of the association between area-level deprivation and breast cancer screening uptake in Europe

Breast cancer rates are lower amongst women from more socio-economically deprived areas. However, their mortality rates are higher. One explanation of this breast cancer paradox is that women from more deprived areas are less likely to attend breast cancer screening programmes. This systematic review is the first to examine this issue in Europe. A systematic review of Embase, Medline and PsychINFO (from 2008 to 2019) was undertaken (PROSPERO registration number: CRD42018083703). Observational studies were included if they were based in Europe, measured breast cancer screening uptake, compared at least two areas, included an area-level measure of socio-economic deprivation and were published in the English language. The Joanna Briggs Institute critical appraisal checklist was used to assess study quality and risk of bias. Thirteen studies from seven different European countries met our inclusion criteria and were included in the review. In ten of the thirteen studies, there was a significant negative association between screening uptake and area-level socio-economic deprivation – with women living in more socio-economically deprived neighbourhoods less likely to attend breast cancer screening. Although universal screening programmes were provided in most studies, there were still strong negative associations between screening uptake and area-level socio-economic deprivation. Future breast cancer screening strategies should acknowledge these challenges, and consider developing targeted interventions in more deprived areas to increase screening participation.     

Cancer mortality 1981–2016 and contribution of specific cancers to current socioeconomic inequalities in all cancer mortality: A population-based study

BackgroundIn many high-income countries cancer mortality rates have declined, however, socioeconomic inequalities in cancer mortality have widened over time with those in the most deprived areas bearing the greatest burden. Less is known about the contribution of specific cancers to inequalities in total cancer mortality.MethodsUsing high-quality routinely collected population and mortality records we examine long-term trends in cancer mortality rates in Scotland by age group, sex, and area deprivation. We use the decomposed slope and relative indices of inequality to identify the specific cancers that contribute most to absolute and relative inequalities, respectively, in total cancer mortality.ResultsCancer mortality rates fell by 24 % for males and 10 % for females over the last 35 years; declining across all age groups except females aged 75+ where rates rose by 14 %. Lung cancer remains the most common cause of cancer death. Mortality rates of lung cancer have more than halved for males since 1981, while rates among females have almost doubled over the same period.ConclusionCurrent relative inequalities in total cancer mortality are dominated by inequalities in lung cancer mortality, but with contributions from other cancer sites including liver, and head and neck (males); and breast (females), stomach and cervical (younger females). An understanding of which cancer sites contribute most to inequalities in total cancer mortality is crucial for improving cancer health and care, and for reducing preventable cancer deaths.     

Ethnic,racial and socioeconomic disparities in breast cancer survival in two Brazilian capitals between 1996 and 2012

ObjectiveTo study the impact of socio-economic status and ethno-racial strata on excess mortality hazard and net survival of women with breast cancer in two Brazilian state capitals.MethodWe conducted a survival analysis with individual data from population-based cancer registries including women with breast cancer diagnosed between 1996 and 2012 in Aracaju and Curitiba. The main outcomes were the excess mortality hazard (EMH) and net survival. The associations of age, year of diagnosis, disease stage, race/skin colour and socioeconomic status (SES) with the excess mortality hazard and net survival were analysed using multi-level spline regression models, modelled as cubic splines with knots at 1 and 5 years of follow-up.ResultsA total of 2045 women in Aracaju and 7872 in Curitiba were included in the analyses. The EMH was higher for women with lower SES and for black and brown women in both municipalities. The greatest difference in excess mortality was seen between the most deprived women and the most affluent women in Curitiba, hazard ratio (HR) 1.93 (95%CI 1.63–2.28). For race/skin colour, the greatest ratio was found in Curitiba (HR 1.35, 95%CI 1.09–1.66) for black women compared with white women. The most important socio-economic difference in net survival was seen in Aracaju. Age-standardised net survival at five years was 55.7% for the most deprived women and 67.2% for the most affluent. Net survival at eight years was 48.3% and 61.0%, respectively. Net survival in Curitiba was higher than in Aracaju in all SES groups.”ConclusionOur findings suggest the presence of contrasting breast cancer survival expectancy in Aracaju and Curitiba, highlighting regional inequalities in access to health care. Lower survival among brown and black women, and those in lower SES groups indicates that early detection, early diagnosis and timely access to treatment must be prioritized to reduce inequalities in outcome among Brazilian women.     

Socioeconomic inequalities in breast cancer survival in Reunion Island: The contribution of stage at diagnosis as a mediator

IntroductionAlthough breast cancer survival has improved in France, it appears that women living in deprived areas are more likely to die from breast cancer. However, no study has yet examined socioeconomic inequalities in breast cancer survival in La Réunion. Our objective was to examine whether socioeconomic inequalities in breast cancer survival exist in Reunion Island and whether stage at diagnosis could partly explain these differences.MethodsA population-based cohort study of all women on Reunion Island with primary breast cancer diagnosed between 2008 and 2016 was conducted. Each woman was assigned a deprivation index based on her area of residence at diagnosis. Net survival by deprivation group and stage at diagnosis was estimated by the non parametric Pohar Perme method. The role of stage (indirect effect) was assessed using a mediation analysis extended to the relative survival framework.ResultsAt five years, net survival was significantly lower in women living in the most deprived areas than in women living in the least deprived areas (81 % (95 % CI 77–86) and 91 % (95 % CI 89–94), respectively, p < 0.0001), and mediation analysis showed that the contribution of stage at diagnosis to these survival differences was 43 %.DiscussionOur result shows that although measures to promote earlier diagnosis are important, they would only reduce socioeconomic inequalities in breast cancer survival by 43 %. To further investigate these inequalities, future research should explore the role of unmeasured mediators, such as comorbidities and treatment received, as well as the impact of specific interventions that might address the differences in mediator distribution.     

Trends in cancer mortality rates among migrants in Australia: 1981-2007

Background: Previous studies have shown that migrants have lower cancer mortality rates compared to the Australian-born population, particularly for colorectal and breast cancers, which are associated with an affluent lifestyle. This study seeks to update knowledge in this field by examining mortality from colorectal, stomach, lung, melanoma, breast and bladder cancers, as well as all cancers combined between 1981 and 2007. Methods: Data were obtained from the Australian Bureau of Statistics. Average annual age and sex-standardised mortality rates were calculated for each region of birth, period of death registration and cancer site. Results: Generally, mortality rates declined over the study period for most conditions for the majority of migrant groups. Notable exceptions included migrants from South Eastern Europe and Eastern Europe who experienced a significant increase in mortality due to all cancers combined and Australian-born individuals who recorded a significant increase in mortality due to melanoma of the skin. Migrants generally had more favourable cancer mortality outcomes, particularly for colorectal cancer and melanoma. Migrants from Southern Europe, South Eastern Europe, Chinese Asia and Southern Asia had the greatest advantage. However, migrants displayed higher rates of stomach, lung and bladder cancers than the Australian-born population. Conclusion: The migrant advantage can in part be explained by the protective effects of diet, lifestyle and reproductive behaviours. Possible explanations for why some migrants display greater mortality from stomach and bladder cancer include the consumption of abrasive, salted and preserved foods and higher rates of smoking. Greater emphasis should be placed on targeting at-risk migrant groups through screening and education programs at migrant resource centres and community groups. The study calls for further research to explain the observed trends, which has the potential to uncover important risk and protective factors.     

Synthesis,antiproliferative and pro-apoptotic activity of 2-phenylindoles

Breast cancer is the second most common cancer worldwide after lung cancer with the vast majority of early stage breast cancers being hormone-dependent. One of the major therapeutic advances in the clinical treatment of breast cancer has been the introduction of selective estrogen receptor modulators (SERMs). We describe the design and synthesis of novel SERM type ligands based on the 2-arylindole scaffold to selectively target the estrogen receptor in hormone dependent breast cancers. Some of these novel compounds are designed as bisindole type structures, while others are conjugated to a cytotoxic agent based on combretastatin A4 (CA4) which is a potent inhibitor of tubulin polymerisation. The indole compounds synthesised within this project such as 31 and 86 demonstrate estrogen receptor (ER) binding and strong antiproliferative activity in the ER positive MCF-7 breast cancer cell line with IC₅₀ values of 2.71 μM and 1.86 μM respectively. These active compounds induce apoptotic activity in MCF-7 cells with minimal effects on normal peripheral blood cells. Their strong anti-cancer effect is likely mediated by the presence of two ER binding ligands for 31 and an ER binding ligand combined with a cytotoxic agent for 86.     

Impact of breast feeding on admission for pneumonia during postneonatal period in Brazil: nested case-control study

ObjectiveTo determine whether breast feeding protects infants against pneumonia and whether the protection varies with age.DesignNested case-control study.SettingPelotas, southern Brazil.SubjectsCases were 152 infants aged 28-364 days who had been admitted to hospital for pneumonia. Controls were 2391 cases in a population based case-control study.ResultsInfants who were not being breast fed were 17 times more likely than those being breast fed without formula milk to be admitted to hospital for pneumonia (95% confidence interval 7.7 to 36.0). This relative risk was 61 (19.0 to 195.5) for children under 3 months old, decreasing to 10 (2.8 to 36.2) thereafter. Supplementation with solids was associated with a relative risk of 13.4 (7.6 to 23.5) for all infants and 175 (21.8 to 1405.1) for those under 3 months old.ConclusionBreast feeding protects young children against pneumonia, especially in the first months of life. These results may be used for targeting intervention campaigns at the most vulnerable age groups.

Key messages

• Pneumonia is the leading cause of death in children under 5 years old across the world
• In Brazil infants who were not breast fed were 17 times more likely than those receiving breast milk alone to be admitted for pneumonia
• The relative risk of admission was 61 for children under 3 months of age, decreasing to 10 thereafter
• Supplementation with solids was associated with a relative risk of 13.4 for all infants
• Mothers must be encouraged to breast feed very young infants and be advised of the right time to introduce supplementary foods

     

Inequality in Diabetes-Related Hospital Admissions in England by Socioeconomic Deprivation and Ethnicity: Facility-Based Cross-Sectional Analysis

ObjectiveTo investigate the effect of social deprivation and ethnicity on inpatient admissions due to diabetes in England.DesignFacility-based cross-sectional analysis.SettingNational Health Service (NHS) trusts in England reporting inpatient admissions with better than 80% data reporting quality from 2010–2011 (355 facilities).ParticipantsNon-obstetric patients over 16 years old in all NHS facilities in England. The sample size after exclusions was 5,147,859 all-cause admissions.ResultsThere were 445,504 diabetes-related hospital admissions in England in 2010, giving a directly (age-sex) standardized rate of 1049.0 per 100,000 population (95% confidence interval (CI): 1046.0–1052.1). The relative risk of inpatient admission in the most deprived quintile was 2.08 times higher than that of the least deprived quintile (95% CI: 2.02–2.14), and the effect of deprivation varied across ethnicities. About 30.1% of patients admitted due to diabetes were readmitted at least once due to diabetes. South Asians showed 2.62 times (95% CI: 2.51 – 2.74) higher admission risk. Readmission risk increased with IMD among white British but not other ethnicities. South Asians showed slightly lower risk of readmission than white British (0.86, 95% CI: 0.80 – 0.94).ConclusionsMore deprived areas had higher rates of inpatient admissions and readmissions due to diabetes. South Asian British showed higher admission risk and lower readmission risk than white British. However, there was almost no difference by ethnicity in readmission due to diabetes. Higher rates of admission among deprived people may not necessarily reflect higher prevalence, but higher admission rates in south Asian British may be explained by their higher prevalence because their lower readmission risk suggests no inequality in primary care to prevent readmission. Better interventions in poorer areas, are needed to reduce these inequalities.     

Stressful life events and difficulties and onset of breast cancer: case-control study

ObjectiveTo determine the relation between stressful life events and difficulties and the onset of breast cancer.DesignCase-control study.Setting3 NHS breast clinics serving west Leeds.Participants399 consecutive women, aged 40-79, attending the breast clinics who were Leeds residents.Results332 (83%) women participated. Women diagnosed with breast cancer were no more likely to have experienced one or more severe life events (adjusted odds ratio 0.91, 95% confidence interval 0.47 to 1.81; P=0.79); one or more severe difficulties (0.86, 0.41 to 1.81; P=0.69); a 2 year severe non-personal health difficulty (0.53, 0.12 to 2.31; P=0.4); or a 2 year severe personal health difficulty (2.73, 0.68 to 10.93; P=0.16) than women diagnosed with a benign breast lump.ConclusionThese findings do not support the hypothesis that severe life events or difficulties are associated with onset of breast cancer.

Key messages

• Although there is widespread belief that stress can cause cancer, research evidence is contradictory
• Stressful life experiences are common; about two thirds of women with a breast lump experienced at least one severe life event or difficulty in the 5 years before presentation
• Women diagnosed with breast cancer were no more likely to have experienced a severe stressor than women with a benign lesion
• Knowledge or suspicion of the diagnosis did not influence reporting of severe life events

     

Women cancers in India: Incidence,trends and their clinical extent from the National Cancer Registry Programme

BackgroundTo provide a comprehensive assessment of women cancer in India utilizing the systematically collected data on all cancers by the National Cancer Registry Programme (NCRP).MethodsThe study examined 10,2287 cancer cases among women cancers providing cancer burden for major anatomical sites. Aggregated data of 28 PBCRs and 58 HBCRs under NCRP for 2012–16 was analysed for incidence rates, trends, cumulative risk of developing cancer, stage at detection and treatments offered.ResultsStudy results have found region –wide variation of women cancers by indicating highest proportions in western followed by southern region of India. North-Eastern region had lowest proportion. It was observed that breast is highest ranking cancer in most registry areas of urban agglomerations of country while cancer cervix was leading site in registries of rural areas like Barshi (15.3) and Osmanabad &Beed (13.1). States of Mizoram (23.2) and Tripura (9.5) along with Pasighat, Cachar and Nagaland. Median age of occurrence for women for these anatomical sites ranged from 45 to 60 years of age. For cancer breast, cervix and ovary –most cases were detected with regional spread. These findings were different for cancer corpus uteri where registries have reported higher proportions (49.3 %) of localized stage at detection. Loco regional cancers had higher proportions of multimodality treatments.ConclusionStudy provides a foundation for assessing the status of women cancers in the country. Variations between geographies would guide appropriate support for action to strengthen efforts to improve cancer prevention and control in underserved areas of the country. This would facilitate advocacy for better investments and research on women cancers.     

Lack of ADAM2, CALR3 and SAGE1 Cancer/Testis Antigen Expression in Lung and Breast Cancer

Immunotherapy is emerging as a supplement to conventional cancer treatment, and identifying antigen targets for specific types of cancer is critical to optimizing therapeutic efficacy. Cancer/testis antigens are highly promising targets for immunotherapy due to their cancer-specific expression and antigenic properties, but the expression patterns of most of the more than 200 identified cancer/testis antigens in various cancers remain largely uncharacterized. In this study, we investigated the expression of the cancer/testis antigens ADAM2, CALR3 and SAGE1 in lung and breast cancer, the two most frequent human cancers, with the purpose of providing novel therapeutic targets for these diseases. We used a set of previously uncharacterized antibodies against the cancer/testis antigens ADAM2, CALR3 and SAGE1 to investigate their expression in a large panel of normal tissues as well as breast and lung cancers. Staining for the well-characterized MAGE-A proteins was included for comparison. Immunohistochemical staining confirmed previous mRNA analysis demonstrating that ADAM2, CALR3 and SAGE1 proteins are confined to testis in normal individuals. Negative tissues included plancenta, which express many other CT antigens, such as MAGE-A proteins. Surprisingly, we detected no ADAM2, CALR3 and SAGE1 in the 67 lung cancers (mainly non-small lung cancer) and 189 breast cancers, while MAGE-A proteins were present in 15% and 7–16% of these tumor types, respectively. Treatment with DNA methyltransferase inhibitors has been proposed as an attractive strategy to increase the expression of cancer/testis antigens in tumors before immunotargeting; however, neither ADAM2, CALR3 nor SAGE1 could be significantly induced in lung and breast cancer cell lines using this strategy. Our results suggest that ADAM2, CALR3 and SAGE1 cancer/testis antigens are not promising targets for immunotherapy of breast and lung cancer.     

Urinary Nucleosides as Biomarkers of Breast,Colon, Lung,and Gastric Cancer in Taiwanese

Urinary nucleosides are associated with many types of cancer. In this study, six targeted urinary nucleosides, namely adenosine, cytidine, 3-methylcytidine, 1-methyladenosine, inosine, and 2-deoxyguanosine, were chosen to evaluate their role as biomarkers of four different types of cancer: lung cancer, gastric cancer, colon cancer, and breast cancer. Urine samples were purified using solid-phase extraction (SPE) and then analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The Mann-Whitney U test and Principal Component Analysis (PCA) were used to compare differences in urinary nucleosides between patients with one of four types of cancer and healthy controls. The diagnostic sensitivity of single nucleosides for different types of cancer ranged from 14% to 69%. In contrast, the diagnostic sensitivity of a set of six nucleosides ranged from 37% to 69%. The false-positive identification rate associated with the set of six nucleosides in urine was less than 2% compared with that of less than 5% for a single nucleoside. Furthermore, combining the set of six urinary nucleosides with carcinoembryonic antigen improved the diagnostic sensitivity for colon cancer. In summary, the study show that a set of six targeted nucleosides is a good diagnostic marker for breast and colon cancers but not for lung and gastric cancers.