Reviews & Analysis

One year of adjuvant trastuzumab, preferentially given upfront with a taxane as part of an anthracycline–taxane containing chemotherapy, is currently considered standard therapy for treating early-stage breast cancer. The long-awaited full publication of the BCIRG-006 trial now establishes the TCH (docetaxel, carboplatin, trastuzumab) regimen as an additional option with a distinct safety profile.boxed-text

Bone-targeting treatments have transformed the quality of life of patients with metastatic bone disease. 2011 saw the emergence of denosumab—a RANK ligand-specific antibody—as a more-effective alternative treatment to bisphosphonates and of data on the use of bone-targeting treatments to prevent metastasis from breast and prostate cancers.

Highly clinically relevant ovarian cancer clinical research in 2011 focused on an increased understanding of the biology of the malignancy, limitations of strategies for early detection and screening, and the provocative reports of alternative primary and second-line management strategies.

This Review article approaches the area of targeted therapies from two angles: efficacy and side effects. The authors outline the successes that have been achieved in treating cancer with targeted therapies and also discuss the pitfalls and quality of life issues that still need to be addressed.

A recent study of 843 patients from three hospitals that compared the assessment of HER2 status using FDA-approved immunohistochemistry and fluorescence in situ hybridization assays versus a quantitative reverse transcription PCR (qRT-PCR) assay by Oncotype DX^®, showed a high false negative rate for the qRT-PCR assay.

A new phase III study shows superior efficacy of fludarabine plus alemtuzumab combination therapy over fludarabine alone in the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL). However, the study has limitations and the findings can not be generalized to the majority of patients with CLL.

Gene-expression profiling has led to the development of signatures designed to predict survival and treatment response in patients with breast cancer. In this Review, Prat et al. discuss the clinical utility of gene-expression-based assays and compare them with the performance of breast cancer biomarkers that are currently used as standard of care.

If a targeted therapy demonstrates convincing efficacy in early clinical testing, can randomized phase III trials be avoided? Sharma and Schilsky discuss when it is reasonable to consider foregoing randomized phase III trials before drug approval and also highlight the caveats. They explore the consequences of such an approach and propose criteria that the drugs must meet to be approved without a phase III trial.

Although breast density is a powerful factor for predicting the risk of developing breast cancer, unfortunately current methods of measuring mammographic density are not entirely satisfactory. This Review analyzes the different factors affecting breast density and how to consider them so that the accuracy of individual risk assessments can be improved.

Rates of central nervous system (CNS) involvement in metastatic cancer are believed to be increasing. The neurosurgical treatment of patients with metastatic cancer is an integral component of multimodality therapy for brain and spinal metastases. This Review discusses data from current randomized clinical trials that examine the role of neurosurgical intervention in the treatment of patients with CNS metastases.

The ECOG E4201 study adds another piece of information to a growing body of evidence pointing strongly to the importance of local control and the role of radiotherapy in unresectable pancreatic cancer. Based on this evidence, we believe radiotherapy should be used routinely in this setting.boxed-text

Screening for prostate cancer using PSA is a careful balance of benefits and harms. But current US practice involves testing older men who have little to gain and aggressively treating low-risk cancers. Debates about whether to test need to be replaced by debates on how to test better.

Despite the advent of HER2-directed therapies, many patients with HER2-positive early stage breast cancer relapse and die of this disease. Trials to define, refine and optimize the use of the approved HER2-targeted agents are ongoing. New approaches are being developed and a series of large trials in the adjuvant and neoadjuvant settings are planned or in progress. In this Review, Arteaga et al. describe the current treatment for HER2-positive breast cancer and provide an update on ongoing clinical trials and translational research.

This Review discusses recent evidence that indicates that different genetic alterations might be related to distinct sensitivity to targeted therapies. It examines prototypical examples and asks what is the role of cancer mutations as predictors of sensitivity and resistance to targeted therapies? Further, what are the implications for the 'personalized' treatment of cancer patients?

The AZURE trial data add to the uncertainty of whether adjuvant bisphophonates are a valuable addition to the armamentarium in the treatment of early stage breast cancer. Although the overall trial results were negative, a prespecified subgroup analysis demonstrated a 25% reduction in the risk of relapse and death in postmenopausal patients.

The size, length and cost of phase III clinical trials are prompting oncology researchers and pharmaceutical companies to look for other options. This Review outlines adaptive clinical trial designs that can address many questions at once. A wholly new paradigm for drug development exemplifying personalized medicine is evinced by an adaptive trial called I-SPY2, in which drugs from many companies are evaluated in the same study and are matched with their biomarker signatures.

Radioimmunotherapy is being used successfully for the treatment of patients with hematological malignancies, however similar efficacy is lacking in patients with solid tumors. Pouget and colleagues explain basic concepts of radiobiology, review the results of clinical radioimmunotherapy trials, and highlight potential strategies to improve the efficacy of radioimmunotherapy in patients with solid tumors.

In a trial in patients with metastatic breast cancer, the prognostic value of the number of circulating tumor cells (CTCs) at baseline was independent of tumor subtype, except in patients with HER2-positive disease treated with anti-HER2 targeted therapy. These data support the use of CTC detection as a tool contributing to personalized medicine.

The Cancer Act that was signed by President Nixon in December 1971 had a mandate “to support research and the application of the results of research, to reduce the incidence, morbidity and mortality from cancer.” It has succeeded in many of these aims, as this personal account testifies.

Carcinomas of an unknown primary origin (CUP) are histologically confirmed metastases for which a primary tumor could not be found despite an extensive diagnostic workup of the patient. The authors of this Review discuss the clinical evaluation of patients with CUP, describe how to identify specific CUP subsets, and outline treatment strategies and outcomes of patients with CUP.