Reviews & Analysis

Development of therapies directed to specific molecular abnormalities within cancer cells, as exemplified by human epidermal growth factor receptor 2 (HER2), can be a very rewarding strategy in cancer treatment. The integration of genomic and proteomic approaches into the search for therapeutic targets will be more fruitful than either approach alone and allow further individualization of breast cancer therapy.

Substantial progress has been made using aromatase inhibitors in early-stage breast cancer. This article highlights results from recent and ongoing trials of aromatase inhibitors as adjuvant therapy and discusses options for integration of these agents with tamoxifen in various subsets of patients and clinical scenarios.

As our understanding of cancer evolves, the perceptions and prevailing paradigms that define this disease have also changed. The molecular basis of cancer has helped to influence oncology clinical practice; however, paradigms affect both the focus and design of research and also impact upon patient care. A clear recognition of how these varying perceptions of cancer affect and limit communication among the cancer-related disciplines as well as between these disciplines is needed. Both professionals and the general public should consider cancer as a group of diseases for which cure is related to tumor type, stage and available treatment.

Breast cancer is a multifactorial condition, and changes in cellular biology are affected by a large number of variables known to affect an individual's susceptibility to this malignancy. Current risk prediction models are based on combinations of risk factors and have good predictive but low discriminatory power. Risk estimation might be improved by incorporating additional factors into risk prediction models, which will allow better determination of breast cancer risk and provide new targets for preventive therapies.

Important changes in the field of epidemiology as a result of genotyping, identification of genetic and gene-environment causes of disease, and proteomics will ultimately influence all aspects of medical practice. The necessity for good study design, and the difference between observation and experiment, is paramount in this regard. This review discusses opportunities for molecular classification of disease that will help tailor treatment to the biologic profile of the patient and disease.

The evidence for prostate cancer screening using prostate-specific antigen with reference to UK criteria is presented. Such screening might result in considerable over-diagnosis and over-treatment of clinically insignificant prostate cancer. Morbidity associated with treatment of suspected prostate cancer is substantial, so the likelihood of harm may outweigh the prospect of benefit.

This Viewpoint assesses whether prostate cancer screening within the US is justifiable outside clinical trials. Prostate-specific antigen (PSA) values may fluctuate for physiologic reasons and the natural history of the disease varies between individuals. PSA testing increasingly identifies too many cases of indolent disease that would never have threatened patients' lives.

The identification of somatic mutations in the epidermal growth factor receptor (EGFR) gene and promising clinical trial data showing a favorable clinical response to associated gefitinib and erlotinib in non-small-cell lung cancer patients was a major breakthrough in the field. Should patient selection for treatment with these drugs, however, be solely based on mutational EGFR status? Giaccone and Rodriguez discuss ways in which mutational analysis could be optimized, highlight factors that might help define sensitivity to EGFR inhibitors, and comment on how to select those patients who would benefit from treatment.

Prodrugs of 5-fluorouracil (5-FU) have been shown to be as effective as bolus 5-FU and folinic acid (FA) both in the metastatic and adjuvant setting for colon cancer treatment. Currently, oxaliplatin/5-FU is regarded as the standard adjuvant treatment, and improved response rates and prolonged survival support the use of irinotecan or oxaliplatin combined with 5-FU/FA. The use of oral compounds of 5-FU with irinotecan and oxaliplatin in patients with metastatic disease, however, is questionable due to toxicity concerns. Folprecht and Köhne explain why fluoropyrimidines remain an important component of first-line treatment and discuss which patients would benefit from monotherapy with fluoropyrimidines.

Based on preclinical data, it has been suggested that antiangiogenic compounds could improve cytotoxic drug delivery because of their effects on tumor endothelium. Most of the early clinical testing of these agents was conducted in patients with advanced disease resistant to standard therapies, and while some of the phase III trial data were disappointing, recent studies validated in large clinical trials with the anti-VEGF antibody, bevacizumab, demonstrated significant clinical benefit and renewed enthusiasm for this therapeutic strategy. This review highlights the challenges related to choosing appropriate strategies for the selection of patients, study design, and choice of appropriate endpoints for the study development of these agents.

Evaluating the prognostic value of a tumor marker is an important component of oncology research and has an important impact on treatment decisions. The authors discuss whether the usual statistical approach used to assess prognostic markers can enhance predictive accuracy, and they describe the merits of a more direct approach.

The best practice for use of oncology guidelines is discussed in this Viewpoint article. Clinical practice guidelines should not be used as cost-savings devices, but as tools for ensuring the best care of each individual patient. Guidelines should be accessible, flexible and allow participation of those intended to use them.

The treatment of head and neck cancer requires a multidisciplinary approach, and positron emission tomography/CT is a rapidly evolving technique that is profoundly altering the staging, radiation treatment planning and clinical management decisions for this disease. Franket al. discuss the use of PET/CT for staging and detecting both primary or recurrent head and neck cancer and its applications in radiotherapy treatment planning.