Molecular subtyping of breast cancer: Opportunities for new therapeutic approaches

Evidence is accumulating that breast cancer is not one disease but many separate diseases. DNA microarray-based gene expression profiling has demonstrated subtypes with distinct phenotypic features and clinical responses. Prominent among the new subtypes is 'basal-like' breast cancer, one of the 'intrinsic' subtypes defined by negativity for the estrogen, progesterone, and HER2/neu receptors and positivity for cytokeratins-5/6. Focusing on basal-like breast cancer, we discuss how molecular technologies provide new chemotherapy targets, optimising treatment whilst sparing patients from un-necessary toxicity. Clinical trials are needed that incorporate long-term follow-up of patients with well-characterised tumour markers. Whilst the absence of an obvious dominant oncogene driving basallike breast cancer and the lack of specific therapeutic agents are serious stumbling blocks, this review will highlight several promising therapeutic candidates currently under evaluation. Thus, new molecular technologies should provide a fundamental foundation for better understanding breast and other cancers which may be exploited to save lives.

Approaches to the Implementation of the Water Framework Directive: Targeting Mitigation Measures at Critical Source Areas of Diffuse Phosphorus in Irish Catchments

The Water Framework Directive (WFD) has initiated a shift towards a targeted approach to implementation through its focus on river basin districts as management units and the natural ecological characteristics of waterbodies. Due to its role in eutrophication, phosphorus (P) has received considerable attention, resulting in a significant body of research, which now forms the evidence base for the programme of measures (POMs) adopted in WFD River Basin Management Plans (RBMP). Targeting POMs at critical sources areas (CSAs) of P could significantly improve environmental efficiency and cost effectiveness of proposed mitigation strategies. This paper summarises the progress made towards targeting mitigation measures at CSAs in Irish catchments. A review of current research highlights that knowledge related to P export at field scale is relatively comprehensive however; the availability of site-specific data and tools limits widespread identification of CSA at this scale. Increasing complexity of hydrological processes at larger scales limits accurate identification of CSA at catchment scale. Implementation of a tiered approach, using catchment scale tools in conjunction with field-by-field surveys could decrease uncertainty and provide a more practical and cost effective method of delineating CSA in a range of catchments. Despite scientific and practical uncertainties, development of a tiered CSA-based approach to assist in the development of supplementary measures would provide a means of developing catchment-specific and cost-effective programmes of measures for diffuse P. The paper presents a conceptual framework for such an approach, which would have particular relevance for the development of supplementary measures in High Status Waterbodies (HSW). The cost and resources necessary for implementation are justified based on HSWs’ value as undisturbed reference condition ecosystems.