European journal of cancer : official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
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Multicenter Study
The association between Akt activation and resistance to hormone therapy in metastatic breast cancer.
In this retrospective study, the relationship between Akt activation and the efficacy of endocrine therapy for metastatic breast cancer was investigated. Thirty-six metastatic breast cancer patients, treated with endocrine therapy, were evaluated for the activation of Akt by an immunohistochemical assessment of the expression of phosphorylated Akt at Ser 473 (pAkt). The relationship between the efficacy of endocrine therapy and Akt activation, HER2 status and hormone receptor expression was also investigated. ⋯ These findings, therefore, suggest that Akt activation induces endocrine resistance in metastatic breast cancer, irrespective of the kind of endocrine agents that were administered. Our findings suggest that the activation of Akt in the downstream pathway of HER2 plays an important role in the resistance to endocrine therapy for breast cancer. Although our study was small in scope and retrospective in design, our findings suggest that pAkt may be a useful predictor of resistance to endocrine therapy for breast cancer, while also suggesting that the inhibition of Akt may increase the efficacy of endocrine therapy.
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In the European Union (EU) 20 anticancer agents have been successfully authorised via the Centralised Procedure since its implementation in 1995. Public information on these 20 agents has been reviewed in order to evaluate the effectiveness of the available regulatory mechanisms to facilitate the marketing authorisation of such drugs in the EU. These mechanisms include orphan drug legislation, exceptional circumstances provision and the accelerated evaluation procedure. ⋯ However, this mechanism does not influence the administrative time at the authorities, which accounted for almost one-third of the overall duration of the EU marketing authorisation procedures for oncology drugs. Revision of the EU drug legislation brings about some changes to the above-described provisions, with the potential for an improvement in the current situation. Thus, its implementation offers the chance to reduce the time that innovative oncology agents take to reach the market, although -- based on experience with the current procedures -- more effort is likely to be required to achieve this goal.
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Comparative Study
Is MSI-H of value in predicting the development of metachronous colorectal cancer?
Nearly 10% of patients with colorectal cancer (CRC) develop a metachronous cancer after curative resection of their primary malignancy, however identifying these patients is problematic. Although microsatellite instability (MSI) is associated with the development of multiple CRC, this is predominantly seen in those with hereditary non-polyposis colon cancer (HNPCC). This study has examined the value of MSI analysis in identifying patients at risk of developing metachronous cancer from the general population. ⋯ MSI-H was more prevalent in metachronous cancers, 34/62 compared to 8/71 single cancers (P < 0.0001). The incidence of MSI-H from proximal colon cancers in index metachronous group, 4/22 was similar to single cancer group, 7/71 (P = 0.28), however MSI-H was more commonly identified in index metachronous cancers located distal to the splenic flexure 9/22 than single cancers 1/71 (P < 0.0001). Patients presenting with MSI-H colorectal cancers distal to the splenic flexure are more likely to develop a metachronous cancer and will benefit from surveillance.
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Quality of life (QoL) measurements are increasingly being used as an end point in cancer clinical trials. Standard generic QoL questionnaires may not assess symptoms produced by neuroendocrine tumours. Here we report the development of a disease-specific quality of life score questionnaire for patients with neuroendocrine tumours of the gut to supplement the EORTC core cancer questionnaire, the QLQ-C30. ⋯ Following interviews of 15 health care workers and 35 patients, a 35 question provisional questionnaire was constructed. This was translated into seven European languages and pre-tested in 180 patients resulting in a 21-item module that will be validated in an international clinical trial. The EORTC QLQ-NET21 provides a site-specific module to supplement the QLQ-C30 for patients with neuroendocrine tumours.