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Sweden: cancer statistics from IARC GlobalCan (2012)

Population in 2012: 9.5m
People newly diagnosed with cancer (excluding NMSC) / yr: 50,500
Age-standardised rate, incidence per 100,000 people/yr: 270.0
Risk of getting cancer before age 75:27.8%
People dying from cancer /yr: 22,100

Menu: Swedish Cancer Resources

Swedish Cancer Organisations
Cancer Centres in Sweden
Latest Research Publications from Sweden

Swedish Cancer Organisations (16 links)

Cancer Centres in Sweden (6 links)

Latest Research Publications from Sweden

Dumanski JP, Rasi C, Lönn M, et al.
Mutagenesis. Smoking is associated with mosaic loss of chromosome Y.
Science. 2015; 347(6217):81-3 [PubMed] Related Publications
Tobacco smoking is a risk factor for numerous disorders, including cancers affecting organs outside the respiratory tract. Epidemiological data suggest that smoking is a greater risk factor for these cancers in males compared with females. This observation, together with the fact that males have a higher incidence of and mortality from most non-sex-specific cancers, remains unexplained. Loss of chromosome Y (LOY) in blood cells is associated with increased risk of nonhematological tumors. We demonstrate here that smoking is associated with LOY in blood cells in three independent cohorts [TwinGene: odds ratio (OR) = 4.3, 95% confidence interval (CI) = 2.8 to 6.7; Uppsala Longitudinal Study of Adult Men: OR = 2.4, 95% CI = 1.6 to 3.6; and Prospective Investigation of the Vasculature in Uppsala Seniors: OR = 3.5, 95% CI = 1.4 to 8.4] encompassing a total of 6014 men. The data also suggest that smoking has a transient and dose-dependent mutagenic effect on LOY status. The finding that smoking induces LOY thus links a preventable risk factor with the most common acquired human mutation.

Related: Chromosome Y Lung Cancer

Liede A, Bach BA, Stryker S, et al.
Regional variation and challenges in estimating the incidence of giant cell tumor of bone.
J Bone Joint Surg Am. 2014; 96(23):1999-2007 [PubMed] Related Publications
BACKGROUND: Estimating the incidence of giant cell tumor of bone is challenging because few population-based cancer registries record benign bone tumors. We compared two approaches, the indirect (relative index) estimation approach used in The Burden of Musculoskeletal Diseases in the United States (BMUS) and a direct incidence rate approach (from registries that record giant cell tumor), to estimate giant cell tumor incidence in France, Germany, Italy, Spain, the U.K., Sweden, Australia, Canada, Japan, and the U.S.
METHODS: Giant cell tumor of bone incidence was calculated with use of the BMUS relative index of giant cell tumor to osteosarcoma in three scenarios (low, base case, and high) from case series. We compared the BMUS approach with the latest data from tumor registries in Australia (1972 to 1996), Japan (2006 to 2008), and Sweden (1993 to 2011) that record giant cell tumors. United Nations population estimates were used to project results to 2013.
RESULTS: The low scenario in the BMUS approach reflects data from Unni and Inwards; the incidence of giant cell tumor of bone is 0.34 relative to osteosarcoma. As the incidence of osteosarcoma is 31.4% of the total incidence of bone and joint cancers, the incidence of giant cell tumor is 0.11 times that of all bone and joint cancers. The base scenario reflects the series by Mirra et al., with a giant cell tumor incidence of 0.47 relative to osteosarcoma (0.15 to all bone and joint cancers). The high scenario reflects the series by Ward, with an incidence of 0.84 relative to osteosarcoma (0.26 to all bone and joint cancers). Differences among the three series reflect referral to a national center of excellence compared with referral to a local oncology practice. Registry data indicated a giant cell tumor incidence rate per million per year of 1.33 in Australia, 1.03 in Japan, and 1.11 in Sweden in 2013. The estimated incidence rate per million in the ten countries in 2013 ranged from 1.03 (Japan) to 1.17 (Canada) with use of the registry-based approach and from 0.73 (Japan) for the low scenario) to 2.20 (Germany) for the base case with use of the BMUS approach.
CONCLUSIONS: Giant cell tumor of bone affects approximately one person per million per year in the ten countries studied. Estimates derived with use of age-specific incidences from tumor registries were typically within the range of the low and base case BMUS scenarios. We recommend the registry-derived method for estimating the incidence of giant cell tumor.

Related: Australia Bone Cancers Canada USA

Song H, Zhu J, Lu D
Long-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions.
Cochrane Database Syst Rev. 2014; 12:CD010623 [PubMed] Related Publications
BACKGROUND: Proton pump inhibitors (PPIs) are the most effective drugs to reduce gastric acid secretion. PPIs are one of the most commonly prescribed classes of medications worldwide. Apart from short-term application, maintenance therapy with PPIs is recommended and increasingly used in certain diseases, such as Zollinger-Ellison syndrome and gastro-oesophageal reflux disease, especially for people with erosive oesophagitis or Barrett's oesophagus. Although PPIs are generally safe, their efficacy and safety of long-term use remains unclear. The question of whether the long-term use of PPIs could promote the development of gastric pre-malignant lesions has been widely investigated, but results are inconsistent. Limited insight on this problem leads to a dilemma in decision making for long-term PPI prescription.
OBJECTIVES: To compare the development or progression of gastric pre-malignant lesions, such as atrophic gastritis, intestinal metaplasia, enterochromaffin-like (ECL) cell hyperplasia, and dysplasia, in people taking long-term (six months or greater) PPI maintenance therapy.
SEARCH METHODS: We searched the following databases (from inception to 6 August 2013): the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL. In addition, we searched the reference lists of included trials and contacted experts in the field.
SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) in adults (aged 18 years or greater) concerning the effects of long-term (six months or greater) PPI use on gastric mucosa changes, confirmed by endoscopy or biopsy sampling (or both).
DATA COLLECTION AND ANALYSIS: Two review authors independently performed selection of eligible trials, assessment of trial quality, and data extraction. We calculated odds ratios (OR) for analysis of dichotomous data and mean differences for continuous data, with 95% confidence intervals (CI).
MAIN RESULTS: We included seven trials (1789 participants). Four studies had high risk of bias and the risk of bias in the other three trials was unclear. In addition, it was difficult to assess possible reporting bias. We pooled 1070 participants from four RCTs to evaluate corporal atrophy development revealing an insignificantly increased OR of 1.50 (95% CI 0.59 to 3.80; P value = 0.39; low-quality evidence) for long-term PPI users relative to non-PPI users. In five eligible trials, corporal intestinal metaplasia was assessed among 1408 participants, also with uncertain results (OR 1.46; 95% CI 0.43 to 5.03; P value = 0.55; low-quality evidence). However, by pooling data of 1705 participants from six RCTs, our meta-analysis showed that participants with PPI maintenance treatment were more likely to experience either diffuse (simple) (OR 5.01; 95% CI 1.54 to 16.26; P value = 0.007; very-low-quality evidence) or linear/micronodular (focal) ECL hyperplasia (OR 3.98; 95% CI 1.31 to 12.16; P value = 0.02; low-quality evidence) than controls. No participant showed any dysplastic or neoplastic change in any included studies.
AUTHORS' CONCLUSIONS: There is presently no clear evidence that the long-term use of PPIs can cause or accelerate the progression of corpus gastric atrophy or intestinal metaplasia, although results were imprecise. People with PPI maintenance treatment may have a higher possibility of experiencing either diffuse (simple) or linear/micronodular (focal) ECL cell hyperplasia. However, the clinical importance of this outcome is currently uncertain.

Related: Stomach Cancer Gastric Cancer

Johansson AL, Andersson TM, Plym A, et al.
Mortality in women with pregnancy-associated malignant melanoma.
J Am Acad Dermatol. 2014; 71(6):1093-101 [PubMed] Related Publications
BACKGROUND: Malignant melanoma (MM) is one of the most common malignancies in young women. It remains debated whether a MM diagnosed during pregnancy or lactation has a worse prognosis.
OBJECTIVE: We sought to examine mortality in women with pregnancy-associated MM (PAMM) (diagnosed during pregnancy and up to 2-years postpartum).
METHODS: This was a population-based cohort study based on information retrieved from the Swedish Cancer and Multi-Generation Registers. Hazard ratios with 95% confidence intervals adjusted for age, period, education, parity, and tumor location were estimated.
RESULTS: In total, 6857 women and girls aged 15 to 44 years with a diagnosis of cutaneous MM between 1963 and 2009 were identified. Of these, 1019 cases were classified as PAMM. The cause-specific mortality did not differ between PAMM and MM not diagnosed near childbirth (adjusted hazard ratio 1.09, 95% confidence interval 0.83-1.42).
LIMITATIONS: Information on stage at diagnosis was available only for a subset of patients
CONCLUSION: Overall, the cause-specific mortality in women and girls with PAMM did not differ from that in women and girls with non-PAMM. The current findings do not provide evidence of an adverse prognostic influence of pregnancy or a recent birth.

Related: Melanoma Breast cancer in pregnancy Skin Cancer

Fredriksson NJ, Ny L, Nilsson JA, Larsson E
Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types.
Nat Genet. 2014; 46(12):1258-63 [PubMed] Related Publications
Somatic mutations in noncoding sequences are poorly explored in cancer, a rare exception being the recent identification of activating mutations in TERT regulatory DNA. Although this finding is suggestive of a general mechanism for oncogene activation, this hypothesis remains untested. Here we map somatic mutations in 505 tumor genomes across 14 cancer types and systematically screen for associations between mutations in regulatory regions and RNA-level changes. We identify recurrent promoter mutations in several genes but find that TERT mutations are exceptional in showing a strong and genome-wide significant association with increased expression. Detailed analysis of TERT across cancers shows that the strength of this association is highly variable and is strongest in copy number-stable cancers such as thyroid carcinoma. We additionally propose that TERT promoter mutations control expression of the nearby gene CLPTM1L. Our analysis provides a detailed pan-cancer view of TERT transcriptional activation but finds no clear evidence for frequent oncogenic promoter mutations beyond TERT.

Related: Cancer Prevention and Risk Reduction TERT

Brand JS, Humphreys K, Thompson DJ, et al.
Volumetric mammographic density: heritability and association with breast cancer susceptibility loci.
J Natl Cancer Inst. 2014; 106(12) [PubMed] Related Publications
BACKGROUND: Mammographic density is a strong heritable trait, but data on its genetic component are limited to area-based and qualitative measures. We studied the heritability of volumetric mammographic density ascertained by a fully-automated method and the association with breast cancer susceptibility loci.
METHODS: Heritability of volumetric mammographic density was estimated with a variance component model in a sib-pair sample (N pairs = 955) of a Swedish screening based cohort. Associations with 82 established breast cancer loci were assessed in an independent sample of the same cohort (N = 4025 unrelated women) using linear models, adjusting for age, body mass index, and menopausal status. All tests were two-sided, except for heritability analyses where one-sided tests were used.
RESULTS: After multivariable adjustment, heritability estimates (standard error) for percent dense volume, absolute dense volume, and absolute nondense volume were 0.63 (0.06) and 0.43 (0.06) and 0.61 (0.06), respectively (all P < .001). Percent and absolute dense volume were associated with rs10995190 (ZNF365; P = 9.0 × 10(-6) and 8.9 × 10(-7), respectively) and rs9485372 (TAB2; P = 1.8 × 10(-5) and 1.8 × 10(-3), respectively). We also observed associations of rs9383938 (ESR1) and rs2046210 (ESR1) with the absolute dense volume (P = 2.6 × 10(-4) and 4.6 × 10(-4), respectively), and rs6001930 (MLK1) and rs17356907 (NTN4) with the absolute nondense volume (P = 6.7 × 10(-6) and 8.4 × 10(-5), respectively).
CONCLUSIONS: Our results support the high heritability of mammographic density, though estimates are weaker for absolute than percent dense volume. We also demonstrate that the shared genetic component with breast cancer is not restricted to dense tissues only.

Related: Breast Cancer

Johansson M, Fanidi A, Muller DC, et al.
Circulating biomarkers of one-carbon metabolism in relation to renal cell carcinoma incidence and survival.
J Natl Cancer Inst. 2014; 106(12) [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The etiology of renal cell carcinoma (RCC) is only partially understood, but a metabolic component appears likely. We investigated biomarkers of one-carbon metabolism and RCC onset and survival.
METHODS: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 385747 participants with blood samples between 1992 and 2000, and this analysis included 556 RCC case-control pairs. A subsequent replication study included 144 case-control pairs nested within the Melbourne Collaborative Cohort Study (MCCS). Plasma concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine and homocysteine were measured in prediagnostic samples and evaluated with respect to RCC risk using conditional and unconditional logistic regression models, and to all-cause mortality in RCC cases using Cox regression models. All statistical tests were two-sided.
RESULTS: EPIC participants with higher plasma concentrations of vitamin B6 had lower risk of RCC, the odds ratio comparing the 4(th) and 1(st) quartiles (OR4vs1) being 0.40 95% confidence interval [CI] = 0.28 to 0.57, P trend < .001. We found similar results after adjusting for potential confounders (adjusted P trend < .001). In survival analysis, the hazard ratio for all-cause mortality in RCC cases when comparing the 4(th) and 1(st) quartiles (HR4vs1) of vitamin B6 was 0.57 (95% CI = 0.37 to 0.87, P trend < .001). Subsequent replication of these associations within the MCCS yielded very similar results for both RCC risk (OR4vs1 = 0.47, 95% CI = 0.23 to 0.99, P trend = .07) and all-cause mortality (HR4vs1 = 0.56, 95% CI = 0.27 to 1.17, P trend = .02). No association was evident for the other measured biomarkers.
CONCLUSION: Study participants with higher circulating concentrations of vitamin B6 had lower risk of RCC and improved survival following diagnosis in two independent cohorts.

Related: Kidney Cancer

Deperas-Kaminska M, Bajinskis A, Marczyk M, et al.
Radiation-induced changes in levels of selected proteins in peripheral blood serum of breast cancer patients as a potential triage biodosimeter for large-scale radiological emergencies.
Health Phys. 2014; 107(6):555-63 [PubMed] Related Publications
The threat of a large scale radiological emergency, where thousands of people may require fast biological dosimetry for the purpose of triage, makes it necessary to search for new, high throughput biological dosimeters. The authors tested an assay based on the quantitative analysis of selected proteins in peripheral blood serum. They were particularly interested in testing proteins that are specific to irradiation of skin, as these can be used in cases of partial body exposure. Candidate proteins were identified in an earlier study with mice, where skin of the animals was exposed to different doses of radiation and global expression of serum proteins was analyzed. Eight proteins were found, the expression of which showed a consistent dose-response relationship. Human analogues of these proteins were identified, and their expression was measured in peripheral blood serum of 16 breast cancer patients undergoing external beam radiotherapy. The proteins were Apolipoprotein E; Apolipoprotein H; Complement protein 7; Prothrombinase; Pantothenate Kinase 4; Alpha-2-macroglobulin; Fetuin B and Alpha-1-Anti-Chymotrypsin. Measurements were carried out in blood samples collected prior to exposure (control), on the day after one fraction (2 Gy), on the day after five fractions (10 Gy), on the day after 10 fractions (20 Gy), and 1 mo after 23-25 fractions (total dose of 46-50 Gy). Multivariate analysis was carried out, and a multinomial logistic regression model was built. The results indicate that the combined analysis of Apolipoprotein E, Factor X, and Pantothenate Kinase 4 allows discriminating between exposure to 2 Gy and lower and between 10 Gy and higher. The discrimination is possible up to 1 mo after exposure.

Related: Breast Cancer

Akçakaya P, Caramuta S, Åhlen J, et al.
microRNA expression signatures of gastrointestinal stromal tumours: associations with imatinib resistance and patient outcome.
Br J Cancer. 2014; 111(11):2091-102 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Gastrointestinal stromal tumour (GIST) is mainly initialised by receptor tyrosine kinase gene mutations. Although the tyrosine kinase inhibitor imatinib mesylate considerably improved the outcome of patients, imatinib resistance still remains a major therapeutic challenge in GIST therapy. Herein we evaluated the clinical impact of microRNAs in imatinib-treated GISTs.
METHODS: The expression levels of microRNAs were quantified using microarray and RT-qPCR in GIST specimens from patients treated with neoadjuvant imatinib. The functional roles of miR-125a-5p and PTPN18 were evaluated in GIST cells. PTPN18 expression was quantified by western blotting in GIST samples.
RESULTS: We showed that overexpression levels of miR-125a-5p and miR-107 were associated with imatinib resistance in GIST specimens. Functionally, miR-125a-5p expression modulated imatinib sensitivity in GIST882 cells with a homozygous KIT mutation but not in GIST48 cells with double KIT mutations. Overexpression of miR-125a-5p suppressed PTPN18 expression, and silencing of PTPN18 expression increased cell viability in GIST882 cells upon imatinib treatment. PTPN18 protein levels were significantly lower in the imatinib-resistant GISTs and inversely correlated with miR-125a-5p. Furthermore, several microRNAs were significantly associated with metastasis, KIT mutational status and survival.
CONCLUSIONS: Our findings highlight a novel functional role of miR-125a-5p on imatinib response through PTPN18 regulation in GIST.

Related: Gastrointestinal System Cancers Gastrointestinal Stromal Tumors MicroRNAs PDGFRA gene Imatinib (Glivec)

Derolf AR, Laane E, Björklund E, et al.
Dendritic cells in bone marrow at diagnosis and after chemotherapy in adult patients with acute myeloid leukaemia.
Scand J Immunol. 2014; 80(6):424-31 [PubMed] Related Publications
Dendritic cells (DCs) develop in the bone marrow from haematopoietic progenitor cells. Two subsets, plasmacytoid DCs (pDCs) and myeloid DCs (mDCs), have been identified. Little is known regarding DC levels in bone marrow of patients with acute myeloid leukaemia (AML) before and after chemotherapy. We investigated relative pDC and mDC levels in bone marrow from 37 hospital controls and 60 patients with AML [at diagnosis, complete remission (CR) and follow-up] using four-colour flow cytometry. The pDC immunophenotype was characterized as lin-/HLA-DR+/CD123 +  and mDC as lin-/HLA-DR+/CD11c+. In 69% of patients with AML, no DCs were detected at diagnosis. At CR, mDC levels were the same in patients with AML and hospital controls while pDC levels were slightly lower. There was no association between minimal residual disease or survival rates and DC levels. Patients with low mDC levels at CR were more likely to suffer from complicated infections, although the difference was not statistically significant. Altogether, there was a profound decrease in DC levels in patients with AML at diagnosis. DC levels increased at CR and were higher than in hospital controls after post-remission therapy, suggesting that DCs recover after repeated chemotherapy. There may be an association between mDC levels and infectious complications.

Related: Acute Myeloid Leukemia (AML)

Lin Y, Yngve A, Lagergren J, Lu Y
A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of oesophageal cancer.
Br J Nutr. 2014; 112(12):2002-9 [PubMed] Related Publications
Dietary lignans, quercetin and resveratrol have oestrogenic properties, and animal studies suggest that they synergistically decrease cancer risk. A protective effect of lignans on the development of oesophageal cancer in humans has recently been demonstrated, and the present study aimed to test whether these three phytochemicals synergistically decrease the risk of oesophageal cancer. Data from a Swedish nationwide population-based case-control study that recruited 181 cases of oesophageal adenocarcinoma (OAC), 158 cases of oesophageal squamous-cell carcinoma (OSCC), 255 cases of gastro-oesophageal junctional adenocarcinoma (JAC) and 806 controls were analysed. Exposure data were collected through face-to-face interviews and questionnaires. The intake of lignans, quercetin and resveratrol was assessed using a sixty-three-item FFQ. Reduced-rank regression was used to assess a dietary pattern, and a simplified dietary pattern score was categorised into quintiles on the basis of the distribution among the control subjects. Unconditional multivariable logistic regression provided OR with 95% CI, adjusted for all the potential risk factors. A dietary pattern rich in lignans, quercetin and resveratrol was mainly characterised by a high intake of tea, wine, lettuce, mixed vegetables, tomatoes, and whole-grain bread and a low intake of milk. There were dose-dependent associations between simplified dietary pattern scores and all types of oesophageal cancer (all P for trend < 0.05). On comparing the highest quintiles with the lowest, the adjusted OR were found to be 0.24 (95% CI 0.12, 0.49) for OAC, 0.31 (95% CI 0.15, 0.65) for OSCC, and 0.49 (95% CI 0.28, 0.84) for JAC. The results of the present study indicate that a dietary pattern characterised by the intake of lignans, quercetin and resveratrol may play a protective role in the development of oesophageal cancer in the Swedish population.

Related: Cancer of the Esophagus Esophageal Cancer

Hedner C, Gaber A, Korkocic D, et al.
SATB1 is an independent prognostic factor in radically resected upper gastrointestinal tract adenocarcinoma.
Virchows Arch. 2014; 465(6):649-59 [PubMed] Free Access to Full Article Related Publications
Gastric cancer is the second most common cause of cancer-related death worldwide, and the incidence of esophageal adenocarcinoma is rising. While some progress has been made in treatment strategies, overall survival remains very poor for patients with adenocarcinoma in the upper gastrointestinal tract. Special AT-rich sequence binding protein 1 (SATB1) is a global genome organizer that has been demonstrated to promote aggressive tumor behavior in several different types of cancer, including gastric cancer. The prognostic value of SATB1 expression in esophageal cancer has, however, not yet been described. In this study, expression of SATB1 was examined by immunohistochemistry on tissue microarrays prepared from tissue samples from 175 patients with adenocarcinoma of the esophagus, cardia, or stomach and containing normal tissue, intestinal metaplasia, primary tumors, and metastases. A well-validated antibody was used. We found SATB1 to be an independent prognostic factor in patients with a radically resected tumor, correlating with shorter overall survival as well as with shorter recurrence-free survival. SATB1 expression was also found to be significantly lower in primary tumors associated with intestinal metaplasia than those without intestinal metaplasia. This observation is of potential biological interest as it has been proposed that intestinal metaplasia-associated tumors constitute a less aggressive phenotype.

Related: Cancer of the Esophagus Esophageal Cancer Stomach Cancer Gastric Cancer

Van Calster B, Van Hoorde K, Valentin L, et al.
Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study.
BMJ. 2014; 349:g5920 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours.
DESIGN: Observational diagnostic study using prospectively collected clinical and ultrasound data.
SETTING: 24 ultrasound centres in 10 countries.
PARTICIPANTS: Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients.
MAIN OUTCOME MEASURES: Histological classification and surgical staging of the mass.
RESULTS: The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate.
CONCLUSIONS: The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.

Related: Ovarian Cancer

Fu YP, Kohaar I, Moore LE, et al.
The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease.
Cancer Res. 2014; 74(20):5808-18 [PubMed] Article available free on PMC after 15/04/2015 Related Publications
A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P(trend) = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.

Related: Chromosome 19 Bladder Cancer Bladder Cancer - Molecular Biology CCNE1

Lauth M, Toftgard R
Think inside the BOCs: a mechanism underlying medulloblastoma progression.
Dev Cell. 2014; 31(1):1-2 [PubMed] Related Publications
Approximately one-third of medulloblastoma cases are associated with genetic lesions of Hedgehog (Hh) signaling pathway components. In this issue of Developmental Cell, Mille et al. (2014) show that the Hh coreceptor Boc functions specifically in the progression of early- to advanced-stage medulloblastoma by promoting Cyclin D1-dependent DNA damage and genomic instability.

Related: Childhood Medulloblastoma / PNET Medulloblastoma

Scott JG, Fletcher AG, Maini PK, et al.
A filter-flow perspective of haematogenous metastasis offers a non-genetic paradigm for personalised cancer therapy.
Eur J Cancer. 2014; 50(17):3068-75 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
Research into mechanisms of haematogenous metastasis has largely become genetic in focus, attempting to understand the molecular basis of 'seed-soil' relationships. Preceding this biological mechanism is the physical process of dissemination of circulating tumour cells (CTCs) in the circulation. Patterns of metastatic spread have been previously quantified using the metastatic efficiency index, a measure quantifying metastatic incidence for a given primary-target organ pair and the relative blood flow between them. We extend this concept to take into account the reduction in CTCs which occurs in organ capillary beds connected by a realistic vascular network topology. Application to a dataset of metastatic incidence reveals that metastatic patterns depend strongly on assumptions about the existence and location of micrometastatic disease which governs CTC dynamics on the network, something which has heretofore not been considered - an oversight which precludes our ability to predict metastatic patterns in individual patients.

Related: Cancer Prevention and Risk Reduction

Xiong A, Kundu S, Forsberg-Nilsson K
Heparan sulfate in the regulation of neural differentiation and glioma development.
FEBS J. 2014; 281(22):4993-5008 [PubMed] Related Publications
Heparan sulfate proteoglycans (HSPGs) are the main components of the extracellular matrix, where they interact with a large number of physiologically important macromolecules. The sulfation pattern of heparan sulfate (HS) chains determines the interaction potential of the proteoglycans. Enzymes of the biosynthetic and degradation pathways for HS chains are thus important regulators in processes ranging from embryonic development to tissue homeostasis, but also for tumor development. Formation of the nervous system is also critically dependent on intact HSPGs, and several studies have outlined the role of HS in neural induction from embryonic stem cells. High-grade glioma is the most common malignant primary brain tumor among adults, and the outcome is poor. Neural stem cells and glioma stem cells have several common traits, such as sustained proliferation and a highly efficient migratory capacity in the brain. There are also similarities between the neurogenic niche where adult neural stem cells reside, and the tumorigenic niche. These include interactions with the extracellular matrix, and many of the matrix components are deregulated in glioma, e.g. HSPGs and enzymes implementing the biosynthesis and modification of HS. In this article, we will present how HS-regulated pathways are involved in neural differentiation, and discuss their impact on brain development. We will also review and critically discuss the important role of structural modifications of HS in glioma growth and invasion. We propose that targeting invasive mechanisms of glioma cells through modulation of HS structure and HS-mediated pathways may be an attractive alternative to other therapeutic attempts, which so far have only marginally increased survival for glioma patients.

Related: Angiogenesis and Cancer Signal Transduction

Cuzick J, Thorat MA, Andriole G, et al.
Prevention and early detection of prostate cancer.
Lancet Oncol. 2014; 15(11):e484-92 [PubMed] Article available free on PMC after 01/10/2015 Related Publications
Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.

Related: Cancer Screening and Early Detection Prostate Cancer

Skibola CF, Berndt SI, Vijai J, et al.
Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.
Am J Hum Genet. 2014; 95(4):462-71 [PubMed] Article available free on PMC after 02/04/2015 Related Publications
Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

Hallengren E, Almgren P, Engström G, et al.
Fasting levels of high-sensitivity growth hormone predict cardiovascular morbidity and mortality: the Malmö Diet and Cancer study.
J Am Coll Cardiol. 2014; 64(14):1452-60 [PubMed] Article available free on PMC after 02/04/2015 Related Publications
BACKGROUND: Both pathological excess and deficiency of growth hormone (GH) are associated with cardiovascular mortality.
OBJECTIVES: The goal of this study was to test whether fasting levels of growth hormone measured with a high-sensitivity assay (hs-GH) predict cardiovascular morbidity and mortality at the population level.
METHODS: We studied 4,323 participants (age 46 to 68 years; mean age 58 years; 59% women) of the Swedish, population-based Malmö Diet and Cancer study examined in 1991 to 1994. Using multivariate-adjusted Cox proportional hazards models, we related baseline levels of fasting hs-GH to incidence of coronary artery disease, stroke, congestive heart failure, all-cause mortality, and cardiovascular mortality.
RESULTS: During a median follow-up of 16.2 years, hs-GH (hazard ratio [HR]/SD increment of natural logarithm of fasting hs-GH) was independently associated with increased risk of coronary artery disease (397 events; HR: 1.11; 95% confidence interval [CI]: 1.01 to 1.23; p = 0.04), stroke (251 events; HR: 1.18; 95% CI: 1.04 to 1.34; p = 0.01), congestive heart failure (107 events; HR: 1.25; 95% CI: 1.03 to 1.52; p = 0.02), all-cause mortality (645 events; HR: 1.17; 95% CI: 1.08 to 1.26; p < 0.001) and cardiovascular mortality (186 events; HR: 1.43; 95% CI: 1.24 to 1.66; p < 0.001). The addition of hs-GH to a model with conventional cardiovascular risk factors significantly reclassified risk, with a category-free net reclassification improvement (>0) of 0.542 (95% CI: 0.205 to 0.840) in cardiovascular mortality.
CONCLUSIONS: Higher values of hs-GH were associated with an increased risk of cardiovascular morbidity and mortality.

Related: Cancer Prevention and Risk Reduction

Cermignani L, Alberdi C, Demichelis S, et al.
Features related to breast cancer in an entire Argentine rural population.
Anticancer Res. 2014; 34(10):5537-42 [PubMed] Related Publications
AIM: A descriptive study was developed in an entire Argentine rural community considering breast cancer risk factors, preventive strategies and breast cancer incidence.
PATIENTS AND METHODS: the study comprised of 83 women. A questionnaire of 34 items was employed; a mammogram and a breast ultrasound were performed. ANOVA and Pearson correlation were employed.
RESULTS: Mean age was 54.5 years; 69% of women were postmenopausal; 96% had children; breastfeeding was X=10 months/child; Body Mass Index (BMI) was X=27.8 kg/m(2); 13% had first-degree relatives with breast cancer; 90% of women considered mammographic screening a necessary study. One woman had presented breast cancer. Argentine screening guidelines were not followed and an inverse relationship between education level and age of first mammogram was found (p<0.05). Mammographic and ultrasound studies did not reveal potential abnormalities.
CONCLUSION: Peculiar social and cultural characteristics may be relevant to evaluate breast cancer risk factors in Argentina.

Related: Breast Cancer Breast Cancer Screening Cancer Screening and Early Detection

Ansari D, Urey C, Hilmersson KS, et al.
Apicidin sensitizes pancreatic cancer cells to gemcitabine by epigenetically regulating MUC4 expression.
Anticancer Res. 2014; 34(10):5269-76 [PubMed] Related Publications
BACKGROUND/AIM: Mucin 4 (MUC4) has been linked to resistance to gemcitabine in pancreatic cancer cells. The aim of the present study was to assess whether epigenetic control of MUC4 expression can sensitize pancreatic cancer cells to gemcitabine treatment.
MATERIALS AND METHODS: A 76-member combined epigenetics and phosphatase small-molecule inhibitor library was screened for anti-proliferative activity against the MUC4(+) gemcitabine-resistant pancreatic cancer cell line Capan-1, followed by high-content screening of protein expression.
RESULTS: Apicidin, a histone deacetylase inhibitor, showed the greatest anti-proliferative activity with a lethal dose 50 (LD50) value of 5.17 μM. Apicidin significantly reduced the expression of MUC4 and its transcription factor hepatocyte nuclear factor 4α. Combined treatment with a sub-therapeutic concentration of apicidin and gemcitabine synergistically inhibited growth of Capan-1 cells.
CONCLUSION: Apicidin appears to be a novel anti-proliferative agent against pancreatic cancer cells that may reverse chemoresistance by epigenetically regulating MUC4 expression.

Related: MUC4 Cancer of the Pancreas Pancreatic Cancer Gemcitabine

Thrift AP, Shaheen NJ, Gammon MD, et al.
Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a mendelian randomization study.
J Natl Cancer Inst. 2014; 106(11) [PubMed] Article available free on PMC after 01/11/2015 Related Publications
BACKGROUND: Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE). However, the relationships may be affected by bias and confounding.
METHODS: We used data from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided.
RESULTS: The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1kg/m(2) increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses.
CONCLUSIONS: People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses.

Related: Cancer of the Esophagus Esophageal Cancer

Eggermont AM, Caldas C, Ringborg U, et al.
Cancer Core Europe: a consortium to address the cancer care-cancer research continuum challenge.
Eur J Cancer. 2014; 50(16):2745-6 [PubMed] Related Publications
European cancer research for a transformative initiative by creating a consortium of six leading excellent comprehensive cancer centres that will work together to address the cancer care-cancer research continuum. Prerequisites for joint translational and clinical research programs are very demanding. These require the creation of a virtual single 'e-hospital' and a powerful translational platform, inter-compatible clinical molecular profiling laboratories with a robust underlying computational biology pipeline, standardised functional and molecular imaging, commonly agreed Standard Operating Procedures (SOPs) for liquid and tissue biopsy procurement, storage and processing, for molecular diagnostics, 'omics', functional genetics, immune-monitoring and other assessments. Importantly also it requires a culture of data collection and data storage that provides complete longitudinal data sets to allow for: effective data sharing and common database building, and to achieve a level of completeness of data that is required for conducting outcome research, taking into account our current understanding of cancers as communities of evolving clones. Cutting edge basic research and technology development serve as an important driving force for innovative translational and clinical studies. Given the excellent track records of the six participants in these areas, Cancer Core Europe will be able to support the full spectrum of research required to address the cancer research- cancer care continuum. Cancer Core Europe also constitutes a unique environment to train the next generation of talents in innovative translational and clinical oncology.

Related: Cancer Prevention and Risk Reduction

Cerhan JR, Berndt SI, Vijai J, et al.
Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.
Nat Genet. 2014; 46(11):1233-8 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

Bonnetain F, Bonsing B, Conroy T, et al.
Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).
Eur J Cancer. 2014; 50(17):2983-93 [PubMed] Related Publications
BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer.
METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9).
RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items.
CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

Related: Cancer of the Pancreas Pancreatic Cancer

San-Miguel JF, Hungria VT, Yoon SS, et al.
Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial.
Lancet Oncol. 2014; 15(11):1195-206 [PubMed] Related Publications
BACKGROUND: Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone. We aimed to compare panobinostat, bortezomib, and dexamethasone with placebo, bortezomib, and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma.
METHODS: PANORAMA1 is a multicentre, randomised, placebo-controlled, double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens. Patients were randomly assigned (1:1) via an interactive web-based and voice response system, stratified by number of previous treatment lines and by previous use of bortezomib, to receive 21 day cycles of placebo or panobinostat (20 mg; on days 1, 3, 5, 8, 10, 12, orally), both in combination with bortezomib (1·3 mg/m(2) on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression-free survival (in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators' assessment) and was analysed by intention to treat. The study is ongoing, but no longer recruiting, and is registered at ClinicalTrials.gov, number NCT01023308.
FINDINGS: 768 patients were enrolled between Jan 21, 2010, and Feb 29, 2012, with 387 randomly assigned to panobinostat, bortezomib, and dexamethasone and 381 to placebo, bortezomib, and dexamethasone. Median follow-up was 6·47 months (IQR 1·81-13·47) in the panobinostat group and 5·59 months (2·14-11·30) in the placebo group. Median progression-free survival was significantly longer in the panobinostat group than in the placebo group (11·99 months [95% CI 10·33-12·94] vs 8·08 months [7·56-9·23]; hazard ratio [HR] 0·63, 95% CI 0·52-0·76; p<0·0001). Overall survival data are not yet mature, although at the time of this analysis, median overall survival was 33·64 months (95% CI 31·34-not estimable) for the panobinostat group and 30·39 months (26·87-not estimable) for the placebo group (HR 0·87, 95% CI 0·69-1·10; p=0·26). The proportion of patients achieving an overall response did not differ between treatment groups (235 [60·7%, 95% CI 55·7-65·6] for panobinostat vs 208 [54·6%, 49·4-59·7] for placebo; p=0·09); however, the proportion of patients with a complete or near complete response was significantly higher in the panobinostat group than in the placebo group (107 [27·6%, 95% CI 23·2-32·4] vs 60 [15·7%, 12·2-19·8]; p=0·00006). Minimal responses were noted in 23 (6%) patients in the panobinostat group and in 42 (11%) in the placebo group. Median duration of response (partial response or better) was 13·14 months (95% CI 11·76-14·92) in the panobinostat group and 10·87 months (9·23-11·76) in the placebo group, and median time to response (partial response or better) was 1·51 months (1·41-1·64) in the panobinostat group and 2·00 months (1·61-2·79) in the placebo group. Serious adverse events were reported in 228 (60%) of 381 patients in the panobinostat group and 157 (42%) of 377 patients in the placebo group. Common grade 3-4 laboratory abnormalities and adverse events (irrespective of association with study drug) included thrombocytopenia (256 [67%] in the panobinostat group vs 118 [31%] in the placebo group), lymphopenia (202 [53%] vs 150 [40%]), diarrhoea (97 [26%] vs 30 [8%]), asthenia or fatigue (91 [24%] vs 45 [12%]), and peripheral neuropathy (67 [18%] vs 55 [15%]).
INTERPRETATION: Our results suggest that panobinostat could be a useful addition to the treatment armamentarium for patients with relapsed or relapsed and refractory multiple myeloma. Longer follow up will be necessary to determine whether there is any effect on overall survival.
FUNDING: Novartis Pharmaceuticals.

Related: Myeloma Myeloma - Molecular Biology Bortezomib

Karlsson E, Appelgren J, Solterbeck A, et al.
Breast cancer during follow-up and progression - A population based cohort on new cancers and changed biology.
Eur J Cancer. 2014; 50(17):2916-24 [PubMed] Related Publications
BACKGROUND: Emerging data indicate an important role for biopsies of clinically/radiologically defined breast cancer 'recurrences'. The present study investigates tumour related events (relapses, other malignancies, benign conditions) after a primary breast cancer diagnosis.
PATIENTS AND METHODS: The cohort includes 2102 women, representing all patients, with primary invasive breast cancer during 2000-2011 in the county of Värmland, Sweden. A comparative analysis of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation (Ki67) between the primary tumour and the relapse was performed and related to outcome.
RESULTS: With a mean follow-up time of 4.8 years, 1060 out of 2102 patients have had a biopsy taken after the initial breast cancer diagnosis demonstrating 177 recurrences, 93 other malignancies (colorectal, lung, skin), 40 cancer in situ (skin, breast) and 857 benign lesions. Approximately 70% (177 out of 245) of all cases of relapsed breast cancer underwent a biopsy during this time period. For patients with recurrences, ER (n=127), PR (n=101), HER2 (n=73) and Ki67 (n=55) status in both primary tumour and the corresponding relapse were determined. The discordance of receptor status was 14.2%, 39.6%, 9.6% and 36.3%, respectively. Loss of ER or PR in the relapse resulted in a significant increased risk of death (hazard ratio (HR) 3.62; 95% confidence interval (CI), 1.65-7.94) and (HR 2.34; 95% CI, 1.01-5.47) compared with patients with stable ER or PR positive tumours. The proportion of patients losing ER was bigger in the group treated with endocrine therapy alone or in combination with chemotherapy, 16.7% and 13.3%, respectively, compared with the group treated with chemotherapy alone or that which received no treatment 4.3% and 7.7%, respectively.
CONCLUSION: Discordance of biomarkers between the primary tumour and the corresponding relapse was seen in 10-40% of the patients, adjuvant therapies seem to drive clonal selections. Patients with tumours losing ER or PR during progression have worse survival compared with patients with retained receptor expression.

Related: Breast Cancer MKI67

Glynne-Jones R, Nilsson PJ, Aschele C, et al.
Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up.
Eur J Surg Oncol. 2014; 40(10):1165-76 [PubMed] Related Publications
Squamous cell carcinoma of the anus (SCCA) is a rare cancer but its incidence is increasing throughout the world, and is particularly high in the human immunodeficiency virus positive (HIV+) population. A multidisciplinary approach is mandatory (involving radiation therapists, medical oncologists, surgeons, radiologists and pathologists). SCCA usually spreads in a loco-regional manner within and outside the anal canal. Lymph node involvement at diagnosis is observed in 30%-40% of cases while systemic spread is uncommon with distant extrapelvic metastases recorded in 5%-8% at onset, and rates of metastatic progression after primary treatment between 10 and 20%. SCCA is strongly associated with human papilloma virus (HPV, types 16-18) infection. The primary aim of treatment is to achieve cure with loco-regional control and preservation of anal function, with the best possible quality of life. Treatment dramatically differs from adenocarcinomas of the lower rectum. Combinations of 5FU-based chemoradiation and other cytotoxic agents (mitomycin C) have been established as the standard of care, leading to complete tumour regression in 80%-90% of patients with locoregional failures in the region of 15%. There is an accepted role for surgical salvage. Assessment and treatment should be carried out in specialised centres treating a high number of patients as early as possible in the clinical diagnosis. To date, the limited evidence from only 6 randomised trials [1,2,3,4,5,6,7], the rarity of the cancer, and the different behaviour/natural history depending on the predominant site of origin, (the anal margin, anal canal or above the dentate line) provide scanty direction for any individual oncologist. Here we aim to provide guidelines which can assist medical, radiation and surgical oncologists in the practical management of this unusual cancer.

Related: Anal Cancer

Taflin H, Wettergren Y, Odin E, Derwinger K
Folate levels measured by LC-MS/MS in patients with colorectal cancer treated with different leucovorin dosages.
Cancer Chemother Pharmacol. 2014; 74(6):1167-74 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
PURPOSE: Calcium folinate (leucovorin), which is converted in vivo into biologically active folate, enhances the potency of 5-fluorouracil (5-FU)-based chemotherapy in colorectal cancer. A common dosage of leucovorin in adjuvant and palliative settings is 60 mg/m(2). The aim was to determine the levels of tetrahydrofolate (THF), 5,10-methylenetetrahydrofolate (methyleneTHF), and 5-methyltetrahydrofolate (methylTHF) in tumour and mucosa of colorectal cancer patients who received different dosages of leucovorin intravenously at time of surgery.
METHODS: Eighty patients scheduled for colorectal resection with indication of colorectal cancer were randomised into four groups to receive leucovorin at 0, 60, 200, or 500 mg/m(2), respectively. Blood samples were taken 10 and 30 min after leucovorin administration. Biopsy samples from tumour and mucosa were collected and snap-frozen at surgery. The levels of THF, methyleneTHF, and methylTHF in tumour and mucosa were assessed by liquid chromatography electrospray ionisation tandem mass spectrometry (LC-MS/MS) and the results were related to clinical diagnosis and therapeutic regimens.
RESULTS: The folate levels in tissue revealed extensive inter-individual variability. The mean methyleneTHF value for the four treatment groups were 880, 1,769, 3,024 and 3,723 pmol/gww. Only half of the patients who received 60 mg/m(2) leucovorin had higher levels of methyleneTHF in tumour than patients who received 0 mg/m(2) leucovorin. Rectal cancer patients had significantly lower levels of methyleneTHF compared with colon cancer patients.
CONCLUSIONS: There was a large inter-patient variability of tissue folate levels in colorectal cancer patients after supplementation with leucovorin at standardised dosage. High leucovorin doses were needed to exceed baseline methyleneTHF values, especially in rectal cancer patients. The results indicate that the standardised leucovorin dose may be insufficient to attain the full antitumour effect of 5-FU. Further studies are needed to establish whether higher dosage yields a better treatment response.

Related: Colorectal (Bowel) Cancer Leucovorin

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