Do the British public recognise differences in survival between three common cancers?

Background:

The recognition that cancer is not a single entity, rather that different cancers have different causes and trajectories, has been a key development in the scientific understanding of cancer. However, little is known about the British public''s awareness of differences between cancers. This study examined differences in perceived survivability for three common cancers with widely disparate survival rates (breast, colorectal and lung).

Method:

In a population-based survey, using home interviews (N=2018), respondents answered a quantitative (numeric) question on 5-year survival and a qualitative (non-numeric) question on curability, for each of the three cancers.

Results:

British adults correctly recognised that 5-year survival for breast cancer was higher than for colorectal cancer (CRC), which in turn was recognised to be higher than for lung cancer. Similarly, curability was perceived to be higher for breast than CRC, and both were perceived to be more curable than lung cancer. Awareness of survival differences did not vary by sex, age or socioeconomic status. In terms of absolute values, there was a tendency to underestimate breast cancer survival and overestimate lung cancer survival.

Conclusion:

The British public appear to be aware that not all cancers are equally fatal.     

Comorbidity in elderly cancer patients in relation to overall and cancer-specific mortality

Background:

Aims of this study were to describe the prevalence of comorbidity in newly diagnosed elderly cancer cases compared with the background population and to describe its influence on overall and cancer mortality.

Methods:

Population-based study of all 70+ year-olds in a Danish province diagnosed with breast, lung, colorectal, prostate, or ovarian cancer from 1 January 1996 to 31 December 2006. Comorbidity was measured according to Charlson''s comorbidity index (CCI). Prevalence of comorbidity in newly diagnosed cancer patients was compared with a control group by conditional logistic regression, and influence of comorbidity on mortality was analysed by Cox proportional hazards method.

Results:

A total of 6325 incident cancer cases were identified. Elderly lung and colorectal cancer patients had significantly more comorbidity than the background population. Severe comorbidity was associated with higher overall mortality in the lung, colorectal, and prostate cancer patients, hazard ratios 1.51 (95% CI 1.24–1.83), 1.41 (95% CI 1.14–1.73), and 2.14 (95% CI 1.65–2.77), respectively. Comorbidity did not affect cancer-specific mortality in general.

Conclusion:

Colorectal and lung cancer was associated with increased comorbidity burden in the elderly compared with the background population. Comorbidity was associated with increased overall mortality in elderly cancer patients but not consistently with cancer-specific mortality.     

Symptom lead times in lung and colorectal cancers: what are the benefits of symptom-based approaches to early diagnosis?

Background:

Individuals with undiagnosed lung and colorectal cancers present with non-specific symptoms in primary care more often than matched controls. Increased access to diagnostic services for patients with symptoms generates more early-stage diagnoses, but the mechanisms for this are only partially understood.

Methods:

We re-analysed a UK-based case–control study to estimate the Symptom Lead Time (SLT) distribution for a range of potential symptom criteria for investigation. Symptom Lead Time is the time between symptoms caused by cancer and eventual diagnosis, and is analogous to Lead Time in a screening programme. We also estimated the proportion of symptoms in lung and colorectal cancer cases that are actually caused by the cancer.

Results:

Mean Symptom Lead Times were between 4.1 and 6.0 months, with medians between 2.0 and 3.2 months. Symptom Lead Time did not depend on stage at diagnosis, nor which criteria for investigation are adopted. Depending on the criteria, an estimated 27–48% of symptoms in individuals with as yet undiagnosed lung cancer, and 12–32% with undiagnosed colorectal cancer are not caused by the cancer.

Conclusions:

In most cancer cases detected by a symptom-based programme, the symptoms are caused by cancer. These cases have a short lead time and benefit relatively little. However, in a significant minority of cases cancer detection is serendipitous. This group experiences the benefits of a standard screening programme, a substantial mean lead time and a higher probability of early-stage diagnosis.     

Securin promotes the identification of favourable outcome in invasive breast cancer

Background:

Securin is a recently recognised oncogene with multiple known functions in initiation, progression and cell cycle regulation in several malignant diseases, including breast carcinoma.

Methods:

In this paper, the prognostic value of securin is evaluated by immunohistochemistry in 310 patients diagnosed with invasive breast cancer during a mammographic screening programme in Central Finland. All patients were directed to modern surgical and oncological treatments and were followed up for a maximum of 20 years.

Results:

Our results suggest that securin immunopositivity is an independent prognosticator of invasive breast cancer. In our study, securin predicted breast cancer-specific survival among all cases of invasive breast cancer and subgroups divided according to histological type, Ki-67 proliferation status and tumour size. Especially in a multivariate analysis standardised for axillary lymph node status, patient''s age and tumour size at the time of diagnosis, securin immunopositivity indicated a 13.1-fold risk of breast cancer death (P=0.024) among invasive ductal breast carcinomas with low Ki-67 positivity.

Conclusion:

Our present and previous results suggest that securin could be useful in clinical pathology to intensify the power of the established prognosticators of invasive breast cancer and, especially, to assist in identifying patients with a more favourable outcome than that indicated by Ki-67 alone.     

Brain metastases admissions in Sweden between 1987 and 2006

Background:

Brain metastases (BM) constitute the most common intracranial tumours and are associated with considerable morbidity and mortality. Population-based studies of the epidemiology and time trends of BM are scarce.

Methods:

A population-based cohort of patients admitted to hospital with BM in Sweden between 1987 and 2006 (n=15 517) was identified and linked to nationwide registers of cancer incidence and death. Primary cancer types were assessed and time to hospitalisation and death was computed.

Results:

The annual age-adjusted incidence rate of hospitalisation for BM doubled from 7 to 14 patients per 100 000 between 1987 and 2006. The most common primary tumours among women were lung (33%), breast (33%) and colorectal cancer (7%), and among men lung cancer (44%), malignant melanoma (12%) and colorectal cancer (9%). The increase was most evident for BM patients with lung cancer (both sexes) and breast cancer (women). Survival was short, with a median of 2.7 months. It varied little by cancer type and did not improve over calendar time.

Conclusion:

The number of patients admitted with BM has increased rapidly in Sweden. In spite of recent improvements in the prognosis of common primary cancer types, any parallel improvement among patients with advanced cancer and BM is not indicated.     

A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas

Background:

Circulating tumour cells (CTCs) can provide information on patient prognosis and treatment efficacy. However, there is no universal method to detect CTC currently available. Here, we compared the performance of two CTC detection systems based on the expression of the EpCAM antigen (CellSearch assay) or on cell size (ISET assay).

Methods:

Circulating tumour cells were enumerated in 60 patients with metastatic carcinomas of breast, prostate and lung origins using CellSearch according to the manufacturer''s protocol and ISET by studying cytomorphology and immunolabelling with anti-cytokeratin or lineage-specific antibodies.

Results:

Concordant results were obtained in 55% (11 out of 20) of the patients with breast cancer, in 60% (12 out of 20) of the patients with prostate cancer and in only 20% (4 out of 20) of lung cancer patients.

Conclusion:

Our results highlight important discrepancies between the numbers of CTC enumerated by both techniques. These differences depend mostly on the tumour type. These results suggest that technologies limiting CTC capture to EpCAM-positive cells, may present important limitations, especially in patients with metastatic lung carcinoma.     

Detection of lung,breast, colorectal,and prostate cancers from exhaled breath using a single array of nanosensors

Background:

Tumour growth is accompanied by gene and/or protein changes that may lead to peroxidation of the cell membrane species and, hence, to the emission of volatile organic compounds (VOCs). In this study, we investigated the ability of a nanosensor array to discriminate between breath VOCs that characterise healthy states and the most widespread cancer states in the developed world: lung, breast, colorectal, and prostate cancers.

Methods:

Exhaled alveolar breath was collected from 177 volunteers aged 20–75 years (patients with lung, colon, breast, and prostate cancers and healthy controls). Breath from cancerous subjects was collected before any treatment. The healthy population was healthy according to subjective patient''s data. The breath of volunteers was examined by a tailor-made array of cross-reactive nanosensors based on organically functionalised gold nanoparticles and gas chromatography linked to the mass spectrometry technique (GC-MS).

Results:

The results showed that the nanosensor array could differentiate between ‘healthy'' and ‘cancerous'' breath, and, furthermore, between the breath of patients having different cancer types. Moreover, the nanosensor array could distinguish between the breath patterns of different cancers in the same statistical analysis, irrespective of age, gender, lifestyle, and other confounding factors. The GC-MS results showed that each cancer could have a unique pattern of VOCs, when compared with healthy states, but not when compared with other cancer types.

Conclusions:

The reported results could lead to the development of an inexpensive, easy-to-use, portable, non-invasive tool that overcomes many of the deficiencies associated with the currently available diagnostic methods for cancer.     

Breast cancer incidence and mortality in a transitioning Chinese population: current and future trends

Background:

Projections of future trends in cancer incidence and mortality are important for public health planning.

Methods:

By using 1976–2010 data in Hong Kong, we fitted Poisson age-period-cohort models and made projections for future breast cancer incidence and mortality to 2025.

Results:

Age-standardised breast cancer incidence (/mortality) is projected to increase (/decline) from 56.7 (/9.3) in 2011–2015 to 62.5 (/8.6) per 100 000 women in 2021–2025.

Conclusions:

The incidence pattern may relate to Hong Kong''s socio-economic developmental history, while falling mortality trends are, most likely, due to improvements in survival from treatment advancement and improved health service delivery.     

Survivorship care plans in cancer: a systematic review of care plan outcomes

Background:

Eight years after the Institute of Medicine recommended survivorship care plans (SCPs) for all cancer survivors, this study systematically reviewed the evidence for their use.

Methods:

Studies evaluating outcomes after implementation of SCPs for cancer survivors were identified by searching databases (MEDLINE, EMBASE and Cochrane). Data were extracted and summarised.

Results:

Ten prospective studies (2286 survivors) met inclusion criteria (5 randomised controlled trials (RCTs)). Study populations included survivors of breast, gynaecological, colorectal and childhood cancer. Several models of SCP were evaluated (paper based/on-line, oncologist/nurse/primary-care physician-delivered and different templates). No significant effect of SCPs was found on survivor distress, satisfaction with care, cancer-care coordination or oncological outcomes in RCTs. Breast cancer survivors with SCPs were better able to correctly identify the clinician responsible for their follow-up care. One study suggested a positive impact on reducing unmet needs. Levels of survivor satisfaction with, and self-reported understanding of, their SCP were very high. Feasibility was raised by health professionals as a significant barrier, as SCPs took 1–4 h of their time to develop.

Conclusions:

Emerging evidence shows very few measurable benefits of SCPs. Survivors reported high levels of satisfaction with SCPs. Resource issues were identified as a significant barrier to implementation.     

Low-dose aspirin use and cancer characteristics: a population-based cohort study

Background:

Long-term daily use of aspirin has been associated with reduced cancer mortality. To explore this association, we compared tumour TNM characteristics among aspirin users with those among non-users.

Methods:

From the Swedish Cancer Register, we identified patients diagnosed with colorectal, lung, prostate and breast cancers between 2006 and 2009 and matched them to the Swedish Prescribed Drug Register to obtain information on low-dose aspirin use prior to diagnosis. Contingency table and logistic regression analyses were used to test for association and obtain odds ratios (ORs).

Results:

We identified 17 041 colorectal, 9766 lung, 29 770 prostate and 20 299 breast cancer patients. The proportion of low-dose aspirin users was ∼26% among colorectal, lung and prostate cancer patients and ∼14% among breast cancer patients. Adjusted for age, gender, education level and place of residence, low-dose aspirin use was associated with lower tumour extent (T) for colorectal and lung cancers (P<0.0001) but not for prostate and breast cancers. The adjusted OR of aspirin use for the T4 vs T1 categories was ∼0.7 (95% confidence interval (CI) 0.6–0.8). For all cancers, we found no evidence of association of aspirin use with nodal involvement (N). Except for a borderline result in prostate cancer (OR ∼0.9; 95% CI 0.8–1.0), aspirin use was associated with a lower rate of metastatic disease (ORs ∼0.6–0.8). Among the histological subgroups of lung cancer, significant differences in tumour extent were observed most clearly within the adenocarcinoma subgroup (OR ∼0.6, 95% CI 0.5–0.8), although numbers of other subtypes were more limited; and there was a significant reduction of ∼20–30% in the odds of metastasis among the aspirin users across the subgroups.

Conclusion:

Use of low-dose aspirin in the year prior to diagnosis was found to be associated with lower tumour extent and fewer metastatic disease for colorectal and lung cancers. For these cancers, the benefit of aspirin use appears to be during both early and late cancer progression.     

Cancer survival differences between South Asians and non-South Asians of England in 1986–2004, accounting for age at diagnosis and deprivation

Background:

South Asian migrants show lower cancer incidence than their host population in England for most major cancers. We seek to study the ethnic differences in survival from cancer.

Methods:

We described and modelled the effect of ethnicity, time, age and deprivation on survival for the five most incident cancers in each sex in South Asians in England between 1986 and 2004 using national cancer registry data. South Asian ethnicity was flagged using the validated name-recognition algorithm SANGRA (South Asian Names and Group Recognition Algorithm).

Results:

We observed survival advantage in South Asians in earlier periods. This ethnic gap either remained constant or narrowed over time. By 2004, age-standardised net survival was comparable for all cancers except three in men, where South Asians had higher survival 5 years after diagnosis: colorectal (58.9% vs 53.6%), liver (15.0% vs 9.4%) and lung (15.9% vs 9.3%). Compared with non-South Asians, South Asians experienced a slower increase in breast and prostate cancer survival, both cancers associated with either a screening programme or an early diagnosis test. We did not find differential patterns in survival by deprivation between both ethnicities.

Conclusions:

Considering recent survival trends, appropriate action is required to avoid deficits in cancer survival among South Asians in the near future.     

Ceramide galactosyltransferase (UGT8) is a molecular marker of breast cancer malignancy and lung metastases

Background:

It was shown recently on the level of gene expression that UGT8, coding UDP-galactose:ceramide galactosyltransferase, is one of six genes whose elevated expression correlated with a significantly increased the risk of lung metastases in breast cancer patients. In this study primary tumours and their lung metastases as well as breast cancer cell lines were analysed for UGT8 expression at the protein level.

Methods:

Expression of UGT8 in breast cancer tissue specimens and breast cancer cell lines was analysed using IHC, real-time PCR and Western blotting.

Results:

Comparison of the average values of the reaction intensities (IRS scale) showed a significant difference in UGT8 expression between (1) primary and metastatic tumours (Mann–Whitney U, P<0.05), (2) tumours of malignancy grades G3 and G2 (Mann–Whitney U, P<0.01) as well as G3 and G1 (Mann–Whitney U, P<0.001) and (3) node-positive and node-negative tumours (Mann–Whitney U, P<0.001). The predictive ability of increased expression of UGT8 was validated at the mRNA level in three independent cohorts of breast cancer patients (721). Similarly, breast cancer cell lines with the ‘luminal epithelial-like'' phenotype did not express or weakly expressed UGT8, in contrast to malignant, ‘mesenchymal-like,'' cells forming metastases in nude mice.

Conclusion:

Our data suggest that UGT8 is a significant index of tumour aggressiveness and a potential marker for the prognostic evaluation of lung metastases in breast cancer.     

Elevated expression of myosin X in tumours contributes to breast cancer aggressiveness and metastasis

Background:

Myosin X (MYO10) was recently reported to promote tumour invasion by transporting integrins to filopodial tips in breast cancer. However, the role of MYO10 in tumours remains poorly defined. Here, we report that MYO10 is required in invadopodia to mediate invasive growth and extracellular matrix degradation, which depends on the binding of MYO10''s pleckstrin homology domain to PtdIns(3,4,5)P3.

Methods:

The expression of MYO10 and its associations with clinicopathological and biological factors were examined in breast cancer cells and breast cancer specimens (n=120). Cell migration and invasion were investigated after the silencing of MYO10. The ability of cells to form invadopodia was studied using a fluorescein isothiocyanate-conjugated gelatin degradation assay. A mouse model was established to study tumour invasive growth and metastasis in vivo.

Results:

Elevated MYO10 levels were correlated with oestrogen receptor status, progesterone receptor status, poor differentiation, and lymph node metastasis. Silencing MYO10 reduced cell migration and invasion. Invadopodia were responsible for MYO10''s role in promoting invasion. Furthermore, decreased invasive growth and lung metastasis were observed in the MYO10-silenced nude mouse model.

Conclusions:

Our findings suggest that elevated MYO10 expression increases the aggressiveness of breast cancer; this effect is dependent on the involvement of MYO10 in invadopodial formation.     

Irritable bowel syndrome and the incidence of colorectal neoplasia: a prospective cohort study with community-based screened population in Taiwan

Background:

We aim to report the prevalence of irritable bowel syndrome (IBS) and elucidate the influence of IBS on the incidence of colorectal neoplasm through a community-screening-based, longitudinal follow-up study.

Methods:

We enroled 39 384 community residents aged 40 years or older who had participated in a community-based colorectal cancer-screening programme with an immunochemical faecal occult test since 1999. We followed a cohort that was free of colorectal neoplasm (excluding colorectal neoplasm at baseline) to ascertain the incident colorectal neoplasm through each round of screening and used a nationwide cancer registry. Information on IBS was obtained by linking this screened cohort with population-based health insurance claim data. Other confounding factors were also collected via questionnaire or biochemical tests.

Results:

The overall period prevalence of IBS was 23%, increasing from 14.7% for subjects aged 40–49 years to 43.7% for those aged 70 years and more. After controlling for age, gender and family history of colorectal cancer, screenees who had been diagnosed as having IBS exhibited a significantly elevated level (21% adjusted hazard ratio (HR)=1.21 (95% CI: 1.02–1.42)) of incident colorectal adenoma compared with those who had not been diagnosed with IBS. A similar finding was noted for invasive carcinoma; however, the size of the effect was of borderline statistical significance (adjusted HR=1.20 (95% CI: 0.94–1.53)).

Conclusions:

IBS led to an increased risk for incident colorectal neoplasm.     

The impact of organisational external peer review on colorectal cancer treatment and survival in the Netherlands

Background:

Organisational external peer review was introduced in 1994 in the Netherlands to improve multidisciplinary cancer care. We examined the clinical impact of this programme on colorectal cancer care.

Methods:

Patients with primary colorectal cancer were included from 23 participating hospitals and 7 controls. Hospitals from the intervention group were dichotomised by their implementation proportion (IP) of the recommendations from each peer review (high IP vs low IP). Outcome measures were the introduction of new multidisciplinary therapies and survival.

Results:

In total, 45 705 patients were included (1990–2010). Patients from intervention hospitals more frequently received adjuvant chemotherapy for stage III colon cancer. T2–3/M0 rectal cancer patients from hospitals with a high IP had a higher chance of receiving preoperative radiotherapy (OR 1.31, 95% CI 1.11–1.55) compared with the controls and low IP group (OR 0.75, 95% CI 0.63–0.88). There were no differences in the use of preoperative chemoradiation for T4/M0 rectal cancer. Survival was slightly higher in colon cancer patients from intervention hospitals but unrelated to the phase of the programme in which the hospital was at the time of diagnosis.

Conclusions:

Some positive effects of external peer review on cancer care were found, but the results need to be interpreted cautiously due to the ambiguity of the outcomes and possible confounding factors.     

Emergency presentation of cancer and short-term mortality

Background:

The short-term survival following a cancer diagnosis in England is lower than that in comparable countries, with the difference in excess mortality primarily occurring in the months immediately after diagnosis. We assess the impact of emergency presentation (EP) on the excess mortality in England over the course of the year following diagnosis.

Methods:

All colorectal and cervical cancers presenting in England and all breast, lung, and prostate cancers in the East of England in 2006–2008 are included. The variation in the likelihood of EP with age, stage, sex, co-morbidity, and income deprivation is modelled. The excess mortality over 0–1, 1–3, 3–6, and 6–12 months after diagnosis and its dependence on these case-mix factors and presentation route is then examined.

Results:

More advanced stage and older age are predictive of EP, as to a lesser extent are co-morbidity, higher income deprivation, and female sex. In the first month after diagnosis, we observe case-mix-adjusted excess mortality rate ratios of 7.5 (cervical), 5.9 (colorectal), 11.7 (breast ), 4.0 (lung), and 20.8 (prostate) for EP compared with non-EP.

Conclusion:

Individuals who present as an emergency experience high short-term mortality in all cancer types examined compared with non-EPs. This is partly a case-mix effect but EP remains predictive of short-term mortality even when age, stage, and co-morbidity are accounted for.     

Paired related homoeobox 1, a new EMT inducer,is involved in metastasis and poor prognosis in colorectal cancer

Background:

Paired related homoeobox 1 (PRRX1) has been identified as a new epithelial-mesenchymal transition (EMT) inducer in breast cancer. However, the function of PRRX1 in colorectal cancer (CRC) has not been elucidated.

Methods:

We utilised ectopic PRRX1-expressing cell lines to analyse the function of PRRX1 in CRC. The clinical significance of PRRX1 was also examined on three independent CRC case sets.

Results:

PRRX1 induced EMT and the stem-like phenotype in CRC cells. In contrast to studies of breast cancer, abundant expression of PRRX1 was significantly associated with metastasis and poor prognosis in CRC.

Conclusion:

PRRX1 is an indicator of metastasis and poor prognosis in CRC cases. Further investigation is required to uncover the signalling network regulating PRRX1.