The use of health services among elderly patients with stage IV prostate cancer in the initial period following diagnosis

ObjectiveInformation regarding variability in the type and extent of health services used by elderly patients with advanced prostate cancer (PCa) in the initial period following diagnosis is limited. We evaluated health services utilization among elderly men with stage IV PCa with (M1) and without (M0) distant metastasis during the year following diagnosis.MethodsWe evaluated patients aged 66 and older with incident stage IV PCa during 2005–2007 using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Measures included skilled nursing facility (SNF) stay, hospice stay, and hospitalization. Multivariable logistic regression models were estimated to determine the association between M1 PCa and each health service. Poisson regression was used to assess hospital length of stay.ResultsThe final sample included 3379 patients (20% M0; 80% M1). In the year following diagnosis, M1 patients had greater use of SNF (M0: 8%; M1: 22%), hospice (M0: 5%; M1: 20%), and hospitalization (M0: 43%; M1: 61%). Compared to M0 patients, M1 patients had statistically significantly higher adjusted odds of SNF use (OR = 1.89; 95% CI = 1.38–2.59), hospice use (OR = 3.22; 95% CI = 2.19–4.72), and hospitalization (OR = 1.45; 95% CI = 1.20–1.75). Among those hospitalized, M1 patients had 24% longer length of stay (p < 0.01).ConclusionsThere is 2- to 3-fold greater use of SNF and hospice, and higher hospitalization among M1 compared to M0 patients. Elderly patients with advanced PCa face significant clinical burden within the first year after their diagnosis. Greater understanding of the relationship between clinical disease burden and health services utilization can improve healthcare delivery in this population.     

Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: A systematic review and meta-analysis

BackgroundCardiotoxicity is a well-recognised complication of chemotherapy with anthracycline and/or trastuzumab, and its prevention remains an important challenge in cancer survivorship. Several successful preventative strategies have been identified in animal trials. We sought to assemble the clinical evidence that prophylactic pharmacological interventions could prevent left ventricular (LV) dysfunction and heart failure in patients undergoing chemotherapy.MethodsWe undertook a systemic review of the evidence from randomised trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal ejection fraction and no past history of heart failure. The primary outcome was development of heart failure (HF), a drop in ejection fraction (EF) or both. A random-effects model was used to combine relative risks (RR) and 95% confidence intervals (CIs), and a meta-regression was undertaken to assess the impact of potential covariates.FindingsData were collated from 14 published articles (n = 2015 paediatric and adult patients) comprising 12 randomised controlled trials and two observational studies. The most studied chemotherapeutic agents were anthracyclines, and prophylactic agents included dexrazoxane, statins, beta-blocker and angiotensin antagonists. There were 304 cardiac events in the control arm compared to 83 in the prophylaxis arm (RR = 0.31 [95% CI: 0.25–0.39], p < 0.00001). Cardiac events were reduced with dexrazoxane (RR = 0.35 [95% CI 0.27–0.45], p < 0.00001), beta-blockade (RR = 0.31 [95% CI 0.16–0.63], p = 0.001), statin (RR = 0.31 [95% CI 0.13–0.77], p = 0.01) and angiotensin antagonists (RR = 0.11 [95% CI 0.04–0.29], p < 0.0001).InterpretationProphylactic treatment with dexrazoxane, beta-blocker, statin or angiotensin antagonists appear to have similar efficacy for reducing cardiotoxicity.     

Association analysis between breast cancer genetic variants and mammographic density in a large population-based study (Determinants of Density in Mammographies in Spain) identifies susceptibility loci in TOX3 gene

BackgroundMammographic density (MD) is regarded as an intermediate phenotype in breast cancer development. This association study investigated the influence of 14 breast cancer susceptibility loci identified through previous genome-wide association studies on MD among the participants in the “Determinants of Density in Mammographies in Spain” (DDM-Spain) study.MethodsOur study covered a total of 3348 Caucasian women aged 45–68 years, recruited from seven Spanish breast cancer screening centres having DNA available. Mammographic density was blindly assessed by a single reader using a semiquantitative scale. Ordinal logistic models, adjusted for age, body mass index and menopausal status, were used to estimate the association between each genotype and MD.ResultsEvidence of association with MD was found for variant rs3803662 (TOX3) (Odds Ratio (OR) = 1.13, 95% Confidence Interval (CI) = 1.03–1.25), and marginal evidence of association for susceptibility loci rs3817198 (LSP1) (OR = 1.09, 95% CI = 1.00–1.20) and rs2981582 (FGFR2) (OR = 0.92, 95% CI = 0.84–1.01). Two other loci were associated with MD solely among pre-menopausal women, namely, rs4973768 (SLC4A7) (OR = 0.83, 95% CI = 0.70–1.00) and rs4415084 (MEPS30) (OR = 1.22, 95% CI = 1.00–1.49).ConclusionsOur findings lend some support to the hypothesis which links these susceptibility loci to MD.     

ERCC2 Lys751Gln polymorphism is associated with lung cancer among Caucasians

To derive a more precise estimation of the relationship between the excision repair cross-complementing rodent repair deficiency, group 2 (ERCC2) Lys751Gln polymorphism and lung cancer risk, a meta-analysis was performed. A total of 23 studies including 8137 cases and 9824 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with ERCC2 Gln allele when all studies were pooled into the meta-analysis (Lys/Gln versus Lys/Lys: odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.03–1.19; Gln/Gln versus Lys/Lys: OR = 1.20, 95% CI = 1.06–1.35; dominant model: OR = 1.13, 95% CI = 1.05–1.20; and recessive model: OR = 1.15, 95% CI = 1.03–1.29). In the subgroup analysis by ethnicity, significantly increased risk was only found for Caucasians (Gln/Gln versus Lys/Lys: OR = 1.25, 95% CI = 1.08–1.45; dominant model: OR = 1.10, 95% CI = 1.00–1.22; and recessive model: OR = 1.22, 95% CI = 1.06–1.40). When stratified by study design, statistically significantly elevated risks were found in hospital-based studies (Lys/Gln versus Lys/Lys: OR = 1.12, 95% CI = 1.03–1.22; Gln/Gln versus Lys/Lys: OR = 1.24, 95% CI = 1.06–1.44; dominant model: OR = 1.15, 95% CI = 1.06–1.24; and recessive model: OR = 1.19, 95% CI = 1.03–1.37) and population-based studies (Gln/Gln versus Lys/Lys: OR = 1.57, 95% CI = 1.12–2.20 and recessive model: OR = 1.50, 95% CI = 1.08–2.07). In the subgroup analysis whether or not the studies were matched on smoking, significantly increased risk was found not in those matched studies but in the unmatched studies (Lys/Gln versus Lys/Lys: OR = 1.11, 95% CI = 1.03–1.19; Gln/Gln versus Lys/Lys: OR = 1.22, 95% CI = 1.07–1.40; dominant model: OR = 1.13, 95% CI = 1.05–1.22; and recessive model: OR = 1.18, 95% CI = 1.04–1.33). In conclusion, this meta-analysis suggests that the ERCC2 Lys751Gln polymorphism may contribute to lung cancer susceptibility among Caucasians.     

The TLR4 gene polymorphisms and susceptibility to cancer: A systematic review and meta-analysis

Growing studies revealed the association between polymorphisms in Toll-like receptor 4 (TLR4) and susceptibility to cancer, however, the results remained inconsistent. To assess the effect of six selected SNPs (rs1927914, rs4986790, rs4986791, rs11536889, rs1927911 and rs2149356) in TLR4 on cancer, we conducted a meta-analysis, up to February 2012, 22 case–control studies were available. Summary odds ratios (OR) and corresponding 95% confidence intervals (CIs) for polymorphisms in TLR4 and cancer risk were estimated. Our meta-analysis identified that two SNPs (rs4986790 and rs4986791) in TLR4 were associated with increased cancer risk (for rs4986790: OR = 1.24, 95% CI = 1.01–1.52 in dominant model; OR = 1.24, 95% CI = 1.02–1.52 in overdominant model; for rs4986791: OR = 1.81, 95% CI = 1.18–2.77 in allele comparison; OR = 1.79, 95% CI = 1.15–2.80 in dominant model; OR = 1.70, 95% CI = 1.09–2.67 in overdominant model) and one SNP (rs1927911) in TLR4 was associated with decreased cancer risk (for rs1927911: OR = 0.63, 95% CI = 0.41–0.99 in allele comparison; OR = 0.57, 95% CI = 0.35–0.95 in dominant model; OR = 0.67, 95% CI = 0.46–0.97 in codominant model). Moreover, in terms of stratified analyses by cancer type for SNP rs4986790, significantly elevated risk was observed to be associated with G allele in gastric cancer and ‘other cancers’. These findings indicate that polymorphisms in TLR4 may play a role, although modest, in cancer development.     

Optimal duration of first-line chemotherapy for advanced non-small cell lung cancer: A systematic review with meta-analysis

BackgroundThe optimal duration of first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) has been a matter for debate for nearly 20 years. In order to elucidate this issue, a meta-analysis comparing the different durations of same treatments was performed.MethodsWe searched for all published randomised controlled trials (RCTs) comparing different durations of first-line treatment of advanced NSCLC. The MEDLINE, EMBASE, LILACS and CENTRAL databases were searched for RCTs comparing a defined number of cycles of chemotherapy versus continuing treatment until disease progression, or a defined number of cycles versus a higher number of cycles of the same chemotherapy. Trials including biological agents were excluded.ResultsSeven trials that included 1559 patients were analysed. Treatment for more than 4 cycles was associated with a non-statistically significant decrease in the hazard of mortality relative to shorter treatment (hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.84–1.11; P = .65). In those treated with third-generation chemotherapy through the whole study time, treatment for more than 4 cycles was associated with a non-statistically significant increase in mortality (HR = 1.08; 95% CI = 0.90–1.28; P = .28). Patients receiving more chemotherapy had significant longer progression-free survival (HR = .75; 95% CI = 0.60–0.85; P < 0.0001) than the group with shorter duration of treatment. In an intent-to-treat analysis, there was no difference in the overall response rate between the groups (odds ratio (OR) = 0.78; 95% CI = 0.60–1.01; P = .96). Longer treatment was associated with more severe leucopaenia but with no significant increase in non-haematological toxicities.ConclusionsIn patients with advanced NSCLC the use of more than 4 cycles of first-line chemotherapy with third-generation regimens significantly increases progression-free survival but not overall survival and is associated with higher incidence of adverse events. There is no evidence to support continuous chemotherapy until progression in patients with lung cancer.     

The incidence and relative risk of cardiovascular toxicity in patients treated with new hormonal agents for castration-resistant prostate cancer

AimNew hormonal agents are available for treating metastatic castration-resistant prostate cancer (mCRPC). We aim to define the incidence and relative risk (RR) of cardiovascular events in mCRPC patients treated with these agents.MethodsProspective studies were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods.ResultsWe included six articles in this meta-analysis covering a total of 6735 patients who were used to evaluate cardiac toxicity. The use of new hormonal agents was associated with an increased risk of all grades of such toxicity (RR = 1.32, 95% CI, 1.08–1.60; p = 0.006) compared to a placebo, even if the absolute difference in terms of incidence was small at 14.8% versus 11.5%, respectively. No increased risk of grade 3–4 events (RR = 1.35, 95% CI, 0.90–2.03; p = 0.15) was observed.A total of 7830 patients were used to evaluate hypertension, and it was found that the use of new hormonal agents compared to a placebo was associated with an increased risk of all-grades (RR = 1.84, 95% CI, 1.37–2.46; p < 0.001) and grade 3–4 events (RR = 1.77, 95% CI, 1.13–2.77; p = 0.01). The absolute incidence was 12.5% versus 7.5% for all-grades and 3.7% versus 2.4% for grade 3–4.ConclusionsThis analysis revealed a significant increase in the incidence and RR of cardiovascular toxicity in mCRPC treated with new hormonal agents as opposed to a placebo, even though the occurrence of all- and grade 3–4 events rose only 14% and 4%, respectively. Follow-ups for the onset of treatment-related cardiovascular events should therefore be considered in these patients.     

Clinico-pathological significance of the molecular alterations of the SPOP gene in prostate cancer

AimsSpeckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor recently described to be mutated in prostate cancer (PCa). Hence, studying the gene expression profile and the presence of SPOP mutations in PCa and understanding its clinico-pathological significance as prognostic and therapeutic biomarker are important to further understand its role in PCa development.Patients and methodsA cohort of 265 paraffin-embedded PCa samples from patients with more than 5 years of follow-up and treated with radical prostatectomy were collected at our institution for SPOP evaluation. RT-qPCR analysis was performed for expression studies while mutations were assessed by next generation sequencing. Relationship with prognosis was analysed using log-rank analysis and multivariable Cox regression.ResultsSPOP was found to be strongly down-regulated in PCa (median = 0.24; range = 0.04–9.98) and its expression was associated with both, biochemical (p = 0.003) and clinical progression free survival (p = 0.023), the very low SPOP expression levels being associated to the worst prognosis. Multivariate analysis demonstrated that low levels of SPOP independently predicted a worse prognosis for both, biochemical (Hazard ratio (HR) = 0.5; confidence interval (CI) 95% [0.4–0.9], p = 0.011) and clinical progression (HR = 0.6; IC 95% [0.4–1], p = 0.046). SPOP mutations were found in 10% of TMPRSS2-ERG (T2E)-negative cases. Log-rank tests showed that mutations were significantly associated with biochemical progression free survival (BPFS) (p = 0.009) and also were significant in the multivariable analysis (HR = 3.4; IC 95% [1.5–7.6], p = 0.004).ConclusionsThe present study demonstrates that prognosis varies depending on SPOP expression and mutational status, hence, defining a new biotype of PCa associated with a worse prognosis.     

Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden

BackgroundA worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden.MethodsWe identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010.ResultsThe odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I = 1.6; 95% confidence interval (CI) = 1.5–1.7. OR stage III–IV versus I = 2.3; 95% CI = 1.8–2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high = 2.02; 95% CI = 1.80–2.26; p < 0.0001) and intermediate (HR intermediate versus high = 1.35; 95% CI = 1.20–1.51; p < 0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR = 1.13; 95% CI = 1.01–1.27; p = 0.04) but not for intermediate versus high (HR = 1.11; 95% CI = 0.99–1.24; p = 0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55 years, patients with truncal tumours and during the first 5 years after diagnosis.ConclusionLower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.     

Incidence and mortality of second sarcomas – A population-based study

BackgroundStudies on second sarcoma in unselected populations of cancer survivors have not previously been published.MethodsSecond sarcoma was defined as a sarcoma following a previous invasive cancer. Patients with this malignancy were retrieved from the Cancer Registry in Norway for the period 1960–2007 among a total of 728 874 cancer patients including 11 612 with a sarcoma. Changes in incidence and average annual percent change (AAPC) were studied with join-point analyses. Overall and sarcoma-related mortalities were assessed using the Kaplan–Meier and competing risk methods, respectively.ResultsA total of 900 second sarcomas were identified comprising 7.5% of all sarcomas. The AAPC of second sarcoma incidence was 6.2 (95% CI = 5.7–6.7) as compared to 2.5 (95% CI = 2.1–2.8) for all sarcomas and 2.5 (95% CI = 2.4–2.6) for cancer in general. The annual incidence of second sarcomas doubled during the last decade of the study period. The distribution of histological subtypes was significantly different between second and sporadic sarcomas. The overall mortality was significantly higher and sarcoma-related mortality was significantly lower for patients with a second sarcoma compared to sporadic sarcoma.ConclusionsThere is an increasing incidence of second sarcomas among cancer survivors, and one may speculate a relation to the intensified use of cytotoxic treatment of the preceding malignancy. Sarcoma–related mortality after second sarcomas is significantly below that of sporadic sarcoma.     

FGFR4 transmembrane domain polymorphism and cancer risk: A meta-analysis including 8555 subjects

Fibroblast growth factor receptor 4 (FGFR4), belonging to the receptor tyrosine kinase family, is involved in cancer initiation and progression. The FGFR4 Gly388Arg polymorphism in the transmembrane domain of the receptor was shown to contribute to genetic susceptibility to cancer but the results were inconsistent. We performed a meta-analysis using 12 eligible case-control studies with a total of 4892 patients and 3663 controls to summarise the data on the association between the FGFR4 Gly388Arg polymorphism and cancer risks. The overall odds ratio (OR) with a 95% confidence interval (CI) showed statistical association between the FGFR4 Gly388Arg polymorphism and cancer risks under homozygote comparison, allele contrast and the recessive genetic model. In the subgroup analysis by ethnicity, statistically significantly increased cancer risks were found among Asians for homozygote comparison (OR = 1.43, 95% CI = 1.13–1.80, P_{heterogeneity} = 0.24), allele contrast (OR = 1.16, 95% CI = 1.04–1.29, P_{heterogeneity} = 0.25) and the recessive genetic model (OR = 1.47, 95% CI = 1.19–1.81, P_{heterogeneity} = 0.15). In the subgroup analysis for different tumour types, Arg³⁸⁸ allele had an effect of increasing the risks of breast (homozygote comparison OR = 1.57, 95% CI = 1.04–2.37, P_{heterogeneity} = 0.83 and the recessive model OR = 1.51, 95% CI = 1.02–2.24, P_{heterogeneity} = 0.80) and prostate cancer (Gly/Arg versus Gly/Gly: OR = 1.16, 95% CI = 1.02–1.32, P_{heterogeneity} = 0.74; Arg versus Gly: OR = 1.17, 95% CI = 1.07–1.29, P_{heterogeneity} = 0.18 and the dominant model: OR = 1.20, 95% CI = 1.06–1.35, P_{heterogeneity} = 0.89). Our meta-analysis suggests that the FGFR4 Gly388Arg polymorphism most likely contributes to susceptibility to cancer, especially in Asians. Besides, the Arg³⁸⁸ allele might be associated with increased risks of breast and prostate cancer.     

MDM2 309 T/G polymorphism is associated with lung cancer risk among Asians

Published data on the association between MDM2 309 T/G polymorphism and lung cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of eight studies including 6063 cases and 6678 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with GG variant genotype in recessive model when all the eligible studies were pooled into the meta-analysis (OR = 1.17; 95% CI = 1.02–1.34; P_{heterogeneity} = 0.06). In the subgroup analysis by ethnicity, significantly increased risks were found among Asians for TG versus TT (OR = 1.20; 95% CI = 1.05–1.37; P_{heterogeneity} = 0.30), GG versus TT (OR = 1.34; 95% CI = 1.01–1.79; P_{heterogeneity} = 0.03) and dominant model (OR = 1.26; 95% CI = 1.11–1.43; P_{heterogeneity} = 0.14). However, no significant associations were found in both Europeans and Africans for all genetic models. This meta-analysis suggests that the MDM2 309G allele is a low-penetrant risk factor for developing lung cancer in Asians.     

Reaching women who do not participate in the regular cervical cancer screening programme by offering self-sampling kits: A systematic review and meta-analysis of randomised trials

IntroductionPopulation coverage for cervical cancer screening is an important determinant explaining differences in the incidence of cervical cancer between countries. Offering devices for self-sampling has the potential to increase participation of hard-to-reach women.MethodsA systematic review and meta-analysis were performed to evaluate the participation after an invitation including a self-sampling device (self-sampling arm) versus an invitation to have a sample taken by a health professional (control arm), sent to under-screened women.ResultsSixteen randomised studies were found eligible. In an intention-to-treat analysis, the pooled participation in the self-sampling arm was 23.6% (95% confidence interval (CI) = 20.2–27.3%), when self-sampling kits were sent by mail to all women, versus 10.3% (95% CI = 6.2–15.2%) in the control arm (participation difference: 12.6% [95% CI = 9.3–15.9]). When women had to opt-in to receive the self-sampling device, as used in three studies, the pooled participation was not higher in the self-sampling compared to the control arm (participation difference: 0.2% [95% CI = −4.5–4.9%]).ConclusionAn increased participation was observed in the self-sampling arm compared to the control arm, if self-sampling kits were sent directly to women at their home address. However, the size of the effect varied substantially among studies. Since participation was similar in both arms when women had to opt-in, future studies are warranted to discern opt-in scenarios that are most acceptable to women.     

Mortality is persistently increased in Hodgkin’s lymphoma survivors

BackgroundNegative health outcomes of chronic fatigue (CF) in disease-free cancer survivors are mainly unexplored. Aims of this study were to examine mortality and causes of death in Hodgkin’s lymphoma survivors (HLSs) compared to controls from the general population, and to explore if CF was associated with increased mortality.MethodsHLSs (n = 557) invited to participate in a survey on late effects in 1994 were divided into three groups: participants without CF (n = 329), participants with CF (n = 113), non-participants (n = 98). Controls matched for gender and age were drawn from the general population (five per HLSs, n = 2785). Observation time was calculated from 1st January 1994 until date of death or cut-off at 1st January 2007. Kaplan–Meier plots were used for univariate analyses and Cox models for multiple covariates.ResultsCompared to controls HLSs had nearly five times higher mortality (HR = 4.93; 95% confidence interval [CI]: 3.91–6.21) and the mortality rate of HLSs was higher than the rate of their controls for the entire observation period. Mortality was increased in all groups: participants with CF: HR = 4.85 (95% CI: 3.02–7.77), participants without CF: HR = 4.35 (95% CI: 3.16–6.00), non-participants: HR = 9.45 (95% CI: 5.44–16.41).Compared to the controls HLSs had over six times increased mortality of cancer (HR: 6.6, 95% CI: 4.7–9.2) and almost five times increased mortality of cardiovascular diseases (HR: 4.9, 95% CI: 3.1–7.9).ConclusionsHLSs had almost five-time increased mortality compared to controls. CF was not associated with increased mortality rate. The high mortality among the non-participating HLSs indicates that serious health problems are underestimated in this group. This has implications for the interpretation of surveys in cancer survivors.     

Final 10-year results of the Breast International Group 2–98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer

AimBreast International Group (BIG) 2–98 is a randomised phase III trial that tested the effect of adding docetaxel, either in sequence to or in combination with anthracycline-based adjuvant chemotherapy, in women with node-positive breast cancer (BC). Here, we present the 10-year final trial safety and efficacy analyses. We also report an exploratory analysis on the predictive value of Ki67 for docetaxel efficacy, in the BIG 2–98 and using a pooled analysis of three other randomised trials.Patients and methods2887 patients were randomly assigned in a 2 × 2 trial design to one of four treatments. The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival (DFS). Secondary objectives included comparisons of sequential docetaxel versus sequential control arm, safety and overall survival (OS). Ki67 expression was centrally evaluated by immunohistochemistry.ResultsAfter a median follow-up of 10.1 years, the addition of docetaxel did not significantly improve DFS or OS (hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.81–1.04; P = 0.16 and HR = 0.88, 95% CI = 0.76–1.03; P = 0.11, respectively). Sequential docetaxel did not improve DFS compared to the sequential control arm (HR = 0.86, 95% CI = 0.72–1.03; P = 0.10). In oestrogen receptor (ER)-positive tumours with Ki67 ⩾ 14%, the addition of docetaxel resulted in 5.4% improvement in 10-year OS (P = 0.03, test for interaction = 0.1). In a multivariate model, there was a trend for improved DFS and OS in ER-positive patients with high Ki67 and treated with docetaxel (HR = 0.79, 95% CI = 0.63–1.01; P = 0.05 and HR = 0.76, 95% CI = 0.57–1.01; P = 0.06, respectively). A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours (interaction test P = 0.01).ConclusionThe DFS benefit previously demonstrated with sequential docetaxel is no longer observed at 10 years. However, an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC.     

Which better predicts mortality among older men,a prostate cancer (PCa) diagnosis or vulnerability on the Vulnerable Elders Survey (VES-13)? A retrospective cohort study

ObjectivesOlder men with a prostate cancer (PCa) diagnosis face competing mortality risks. Little is known about the prevalence of vulnerability and predictors of mortality in this population compared to men without a PCa diagnosis. We examined the predictive utility of the Vulnerable Elders Survey (VES-13) for mortality in older men with a PCa diagnosis as compared to controls.Materials and MethodsMen aged ≥ 65 years from an urban geriatrics clinic completed the VES-13 between 2003 and 2008. Each patient with a PCa diagnosis was matched by age to five controls, resulting in 59 patients with a PCa diagnosis and 318 controls. Cox proportional hazard models were used to determine the association of a PCa diagnosis and vulnerability on the VES-13 with mortality.Results and ConclusionsThe mean age for men with a PCa diagnosis and controls was 77.9 years and 76.1 years, respectively. Of those with a PCa diagnosis, 74.6% had no active disease or a rising PSA only. Regardless of PCa diagnosis, vulnerable individuals on the VES-13 were more likely to die during the study period (VES-13 ≥ 3: HR = 4.46, p < 0.01; VES13 ≥ 6: HR = 3.77, p < 0.01). Men with a PCa diagnosis were not more likely to die compared to age-matched controls (VES-13 ≥ 3: HR = 1.14, p = 0.59; VES13 ≥ 6: HR = 1.06, p = 0.83). Vulnerability for men with a PCa diagnosis was more predictive of mortality. Therefore, the assessment of vulnerability is important for establishing goals of care.     

Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer patients: A systematic review

BackgroundAs neoadjuvant chemotherapy (NAC) is increasingly used to downstage patients with breast cancer, the timing of the sentinel node (SN) biopsy has become an important issue. This review was conducted to determine the accuracy of SN biopsy following NAC.MethodsWe searched Medline, Embase and Cochrane databases from 1993 to February 2009 for studies on patients with invasive breast cancer who underwent SN biopsy after NAC followed by an axillary lymph node dissection (ALND).ResultsOf 574 eligible studies, 27 were included in this review with a total study population of 2148 patients. The pooled SN identification rate was 90.9% (95% confidence interval (CI) = 88.0–93.1%) and the false-negative rate was 10.5% (95% CI = 8.1–13.6%). Negative predictive value and accuracy after NAC were 89.0% (95% CI = 85.1–92.1%) and 94.4% (95% CI = 92.6–95.8%), respectively. The reported SN success rates were heterogeneous and several variables were reported to be associated with decreased SN accuracy, i.e. initially positive clinical nodal status.ConclusionsThere is a potential role for SN biopsy following NAC which could be considered on an individual basis. However, there is insufficient evidence to recommend this as a standard procedure. Further research with subgroup analysis using variables reported to be associated with decreased SN accuracy is required in order to clearly define its value in the subgroups of breast cancer patients.     

Functional CYP1A1 genetic variants,alone and in combination with smoking,contribute to development of head and neck cancers

CYP1A1 plays an essential role in pathogenesis of head and neck cancers. Functional CYP1A1 Ile462Val and MspI single nucleotide polymorphisms (SNP) are considered to have significant effects on risk of head and neck cancers. Several case-control studies have examined how these genetic polymorphisms are involved in development of this group of malignancies, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically examine the associations between these functional genetic variants and head and neck cancer risk. A total of 28 studies are eligible for CYP1A1 Ile462Val SNP (4639 patients and 4701 controls), and 22 studies for MspI SNP (4168 patients and 4638 controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were appropriately calculated using either fixed-effect model or random-effect model. There was no association between Ile462Val polymorphism and head and neck cancer risk (OR = 1.23, 95% CI = 0.99–1.53, P = 0.062). However, in a stratified analysis, a statistically significant correlation between this SNP and pharyngeal cancer risk was observed (OR = 1.76, 95% CI = 1.32–2.33, P < 0.001). For MspI SNP, our data indicated that carriers of TC and CC genotypes had a 34% increased risk to develop head and neck cancers compared to TT carriers (95% CI = 1.15–1.57, P < 0.001). This effect was even more pronounced in smokers (OR = 2.98, 95% CI = 1.69–5.26, P < 0.001), demonstrating that gene–smoking interaction intensifying carcinogenesis may exist. These findings reveal that the functional CYP1A1 MspI genetic variant, alone and in combination with smoking, plays a more important role in pathogenesis of head and neck cancers.     

The influence of menopausal hormone therapy on tumour characteristics and survival in endometrial cancer patients

IntroductionMenopausal hormone therapy (MHT) is a well-established factor in endometrial carcinogenesis, and therefore, could have prognostic implications. We investigated the effects of ever use of MHT on tumour grade and depth of myometrial invasion and 5-year relative survival in postmenopausal endometrial cancer patients.Materials and methodsWe used a nationwide, population-based case–case design, of 683 Swedish women aged 50–74 years diagnosed with endometrial cancer during 1994 to 1995, followed up to 5 years after diagnosis. We applied polytomous multiple logistic regression to investigate the associations between the use of MHT and tumour grade, and myometrial invasion and Poisson regression for modelling 5-year excess mortality.ResultsCompared to never use, ever use of any MHT entailed lower risks of having moderately and poorly differentiated tumours. The lowest odds ratios for poorly differentiated tumours were seen for ever users of cyclically combined oestrogen–progestin [OR = 0.23 (95% CI = 0.07 – 0.73)]. Ever users of any form of MHT; particularly, medium potency MHT users, had significantly lower risks for tumours with deep myometrial invasion. Adjusted estimated relative excess hazard ratios revealed significantly improved survival for ever users of any form of MHT [RER = 0.40 (95% CI = 0.16 – 0.97)]; in particular ever users of any form of oestrogens [RER = 0.38 (95% CI = 0.15 – 0.99)].ConclusionEndometrial cancer patients who were ever users of MHT had more favourable tumour characteristics and better survival compared to never users of MHT. These findings support the notion that MHT induces endometrial cancer with less aggressive characteristics.