European follow-up of incorrect biomarker results for colorectal cancer demonstrates the importance of quality improvement projects

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Quality of life during first-line FOLFOX4±panitumumab in RAS wild-type metastatic colorectal carcinoma : results from a randomised controlled trial

Metastatic colorectal cancer is rarely curable. Improving quality of life is therefore a key treatment goal. We report quality of life for patients with RAS wild-type metastatic colorectal cancer in the PRIME study. A randomised phase 3 open-label study of first-line panitumumab+FOLFOX4 vs FOLFOX4 enrolled adults with untreated metastatic colorectal cancer and an Eastern Cooperative Oncology Group performance status of 0-2. This analysis includes patients with wild-type RAS tumours (n=505). Quality of life (prespecified end point) was assessed using the EuroQoL 5-domain health state index and overall health rating in all patients and by early tumour shrinkage status (≥30% reduction in size by week 8; exploratory end point). Differences in quality of life were assessed using analysis of covariance and a mixed-effect piecewise linear model, and were also analysed by skin toxicity severity. There were no statistically significant differences between treatment arms from baseline to progression or to discontinuation. Grade 3+ skin toxicity was reported by 38% of patients receiving panitumumab+FOLFOX4 and 2% receiving FOLFOX4 alone. There were no significant differences in quality of life between patients with grade 0-2 skin toxicity and those with grade 3+ skin toxicity. More patients receiving panitumumab+FOLFOX4 vs FOLFOX4 had early tumour shrinkage (p<.001). In patients with tumour symptoms at baseline, there were statistically significant improvements in quality of life in those with early tumour shrinkage versus those without early tumour shrinkage. Addition of panitumumab to FOLFOX4 in first-line therapy for metastatic colorectal cancer prolongs survival and has no negative effect on overall quality of life compared with FOLFOX4 alone. Specific quality of life assessments for skin toxicity should be included in study designs to better define the direct effect of these adverse events. NCT00364013

Treatment guidelines for adjuvant breast cancer are moving toward double standards: One for the rich and one for the poor [7]

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Shrinking the tumor, shrinking the patient sample size: The early disclosure dilemma [11]

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Progress and new standards of care in the management of HER-2 positive breast cancer.

The aim of this review article is to examine the available evidence regarding diagnosis and treatment of HER-2 positive breast cancer. This group of breast tumours (up to 30% of the total number of breast cancers) is known for having a more aggressive behaviour. The current recommendations for HER-2 positive tumour diagnosis are discussed since accurate identification of HER-2 amplification or overexpression is key for allowing a correct risk assessment and treatment. HER-2 positive tumours can be treated with trastuzumab (Herceptin, Hoffmann-La Roche, Basel, Switzerland), a monoclonal antibody targeted against the HER-2 receptor. The role of this drug in the metastatic, adjuvant and neoadjuvant setting is reviewed. The results of the recently reported adjuvant trials are commented, as the positive results of these trials changed the standard of care for patients with this particular type of breast cancer.Journal ArticleResearch Support, Non-U.S. Gov'tReviewinfo:eu-repo/semantics/publishe

Genomic and molecular classification of breast cancer

At present, the biology of breast cancer remains poorly understood. Currently, lymph node metastases, tumor grade, and size, and expression of hormone receptors provide the only true prognostic and predictive factors related to clinical outcome and response to treatment, respectively. Many other potential candidates have been suggested but, due to their limited predictive power, have not been widely accepted by the general oncological community. These histopathological features do not allow us any insight into breast cancer biology, however, and these prognostic classifications are far from perfect. At present, due to these limitations many clinicians consider prescribing adjuvant treatment to many women with early breast cancer to reduce the risk of relapse, only to benefit a few, thus exposing many patients to unnecessary toxicity. Since the publication of the complete sequence of the human genome however, a new era of research has begun [1]. More than 3 billions base pairs form the 30,000-40,000 genes that code all the required genetic information of a particular individual. The functions of the vast majority of these genes are still unknown. A combination of circumstances, including the advent of array-based technology and progress in the human genome initiative, have provided the ideal opportunity to begin efforts aimed at performing comprehensive molecular and genetic profiling of human cancers. The ability to interrogate tens of thousands of genes simultaneously by using microarray technologies has significantly changed our approach to the analysis of expression profiles, and has also led to an increased understanding of the basic biology of breast cancer. Such comprehensive technologies permit the assessment not only of individual genes, but also of clusters of genes that are coordinately expressed to generate "fingerprints" of biological states of the cells of origin. This is especially important given that it has become increasingly evident that the biology of cancer, particularly solid tumors, is determined by the behavior of many genes, rather than a few. Although there are other techniques that analyze differences in gene expression, none matches the ease and the comprehensive nature of the interrogation associated with c-DNA- or oligonucleotide-based microarray analysis. A list of the terms commonly used in this field is given in Table 30.1. (Table presented). © Springer-Verlag Berlin Heidelberg 2006.SCOPUS: ch.binfo:eu-repo/semantics/publishe

Systematic review and meta-analysis on the proportion of patients with breast cancer who develop bone metastases

A systematic literature review was conducted to quantify populations of patients with primary breast cancer in whom bone metastases were detected at study start or during follow-up. Searches were performed in PubMed and EMBASE using terms related to breast cancer and bone metastases. Articles had to have been published 01/01/99–31/12/13, and to report data on the proportion of patients with bone metastases among patients with breast cancer. In total, 156 articles were included in the meta-analysis. A median of 12% of patients with stage I–III breast cancer developed bone metastases during a median follow-up of 60 months. Of patients who developed metastatic disease during follow-up, 55% (median) had bone metastases. Of those with metastatic breast cancer at study start, 58% (median) had bone metastases. These data help to inform on the global burden of bone metastases by defining patient populations that are at risk of developing bone metastases.SCOPUS: re.jinfo:eu-repo/semantics/publishe