Reviews & Analysis

Members of the nuclear receptor superfamily of transcription factors have been implicated in a broad range of normal physiological and disease processes. There is evidence in support of the involvement of these co-regulators in breast cancer progression. The authors review the role of steroid receptor coactivator-3, which is frequently amplified in breast cancer, and discuss its role in breast cancer risk, outcome and response to endocrine therapy in patients with breast cancer.

Trastuzumab and lapatinib improve survival in patients with HER2-positive breast cancer and there is great interest in developing diagnostic tests that predict which patients are more likely to benefit from specific HER2-directed therapies. This article discusses the predictive role ofHER2mRNA, predictive markers for response to therapy and the mechanisms for overcoming resistance in metastatic disease.

There has been extensive research evaluating the clinical usefulness of genomic biomarkers. High-throughput genomic technologies have revolutionized genomic research but challenges in biomarker assessment include clinical study design, reproducibility and interpretation of results. This Review explores these challenges, focusing on microarray-based gene-expression profiling, and highlights some common failings in study design that have impacted on the clinical use of putative genomic markers.

It has been established that intraperitoneal drug administration is advantageous in patients with tumors confined to the peritoneal cavity. The authors of this Review discuss intraperitoneal drug delivery including the optimal drug, dose and schedule.

Important innovations have been achieved in the development of novel systemic hormonal therapies for the salvage treatment of metastatic castrate-resistant disease. The use of chemotherapy as an adjunct for the treatment of castrate-resistant metastatic disease and local advanced tumors has also resulted in patterns of late toxic effects. The authors review the important advances in the evolution of systemic therapy for the treatment of prostate cancer.

Taxanes are among the most widely used chemotherapy agents for breast cancer. The results of the first-generation taxane trials are reviewed and the authors discuss the possible explanations for the differences observed in these studies. The inclusion criteria for future clinical trials of adjuvant taxane therapy must be revised to account for the molecular heterogeneity of breast cancer.

Stereotactic body radiation therapy has emerged as a novel cancer therapy in the past 10–15 years This review article gives an overview of the background, radiobiologic, technical and clinical aspects of stereotactic body radiation therapy.

Although imatinib mesylate therapy has dramatically improved the prognosis of patients in the advanced phases of chronic myeloid leukemia, room for improvement remains. Tyrosine kinase inhibitors are undergoing evaluation as second-line therapy for patients with imatinib-resistant disease. Kantarjian et al. recently demonstrated that once-daily dasatinib 140 mg is well tolerated and achieves a high response rate.

Sunitinib is a standard first-line therapy for patients with advanced or metastatic clear-cell renal cell carcinoma. In an expanded-access study, sunitinib has demonstrated clinical benefit with an acceptable safety profile in a population of patients that is representative of those seen in clinical practice.

Jørgensen and Gøtzsche quantified the degree of overdiagnosis of breast cancer in five publicly organized mammography screening programs in different parts of the world. Overall, they estimated a total degree of breast cancer (including carcinoma in situ) overdiagnosis of 52%, while overdiagnosis for invasive breast cancer was 35%, a finding with potential implications for both clinical practice and public health.

Bortezomib-based regimens are beneficial in the treatment of patients with symptomatic, newly diagnosed and relapsed or refractory multiple myeloma. Researchers who investigated the efficacy and safety of single-agent bortezomib as first-line therapy in patients with myeloma have particularly emphasized the incidence and management of peripheral neuropathy, which is the most common adverse effect of bortezomib administration.

Targeted agents directed at VEGF and EGFR have become part of the standard treatment of metastatic colorectal cancer; however, only some patients benefit from such treatment. The CAIRO2 and PACCE trials have shown a detrimental effect of adding an anti-EGFR antibody to standard chemotherapy plus bevacizumab. In this Perspective, the authors discuss issues that may explain these unexpected results.

Microarray studies have been used to unravel the molecular characteristics of breast cancer and a molecular taxonomy has been proposed. The authors of this Review discuss the origins of the diversity of breast cancer and, based on the study of histological special types of breast cancer, propose an approach for the identification of novel therapeutic targets.

Radiotherapy is one of the most important and effective therapies used to treat cancer. Particle therapy is an emerging technique and there is debate surrounding its cost-effectiveness. The authors of this Review present clinical results in the field and discuss the research questions that have arisen with this technique.

Six European randomized controlled trials that will compare human papillomavirus (HPV) testing with cytology testing for cervical screening are under way. The outcome of HPV testing versus cytology testing depends not only on the relative accuracy of the primary test but also on how radical the different triage procedures are. Two trials have shown a 50% reduction in grade 3 cervical intraepithelial neoplasia detection in subsequent screening rounds. The authors critically discuss the reasons for the different results observed in these trials and the implications for primary screening.

Gamma-delta lymphomas are rare and aggressive lymphomas with a poor prognosis. The authors of this Review discuss the clinical and biological features of the two types of such lymphomas and the diagnostic challenges associated with these still insufficiently known diseases.

Most patients with advanced colorectal cancer die from hepatic metastases. Radioembolization is a technique for administering radiotherapy internally to unresectable primary or secondary hepatic malignancies in a single procedure to improve local control of disease. This technique enables significant downsizing of liver metastases after surgical resection, and the rationale for this approach combined with cytotoxic and molecularly targeted agents is outlined.

Pooled analyses from the Adjuvant Treatment of Colon Cancer trial suggest that most patients with stage III colon cancer develop recurrence within the first 3 years following treatment. Improved disease-free survival and improved overall survival were observed for such patients who were treated with adjuvant combination therapy of 5-fluorouracil, leucovorin and oxaliplatin versus those treated with 5-fluorouracil and leucovorin.

The monoclonal antibody, rituximab, is used to treat lymphomas. This article discusses the results of randomized trials that suggest patients with follicular lymphoma should not receive rituximab maintenance therapy.

Maintenance therapy aims to sustain a state of ongoing disease remission. This article discusses the results of randomized trials that suggest that specific subgroups of patients with follicular lymphoma should receive maintenance therapy with rituximab.