Review Articles

Basal-like breast cancers are associated with a poor disease-free and overall survival. The pathologic features of breast carcinomas classified by immunohistochemical and gene-expression profiling criteria are critically discussed. The authors emphasize that basal-like tumors display a spectrum of morphologic and clinical characteristics, and that the heterogenous nature of these tumors means the most prognostically relevant subsets have yet to be defined.

Sentinel lymph node biopsy is standard care for intermediate thickness melanoma despite a lack of evidence of its impact on survival. Late-stage disease is frequently wrongly predicted, leading to unnecessary treatments. These issues are discussed here and the author recommends ultrasound-based surveillance after wide excision of the primary tumor for patients assigned false-positive prognoses.

A large number of trials have improved antiemetic therapy and made evidence-based recommendations possible for the majority of patients receiving chemotherapy. This Review discusses the pathophysiology of nausea and vomiting, the development of antiemetics, highlights some of the newest antiemetics, and finally summarizes recommendations from the evidence-based guidelines developed by the Multinational Association of Supportive Care in Cancer.

Molecular imaging can stratify patients according to presence or absence of a drug target, and can distinguish between drug responders and nonresponders. The authors of this Review discuss the integration of molecular imaging in drug development and how this technology can address key questions in the preclinical and clinical evaluation of new targeted drugs.

Cervical cancer is a major cause of cancer mortality and is initiated by infection with high-risk human papillomaviruses (HPVs). An improved understanding of the virologic basis for this disease will help with prevention and treatment. This Review summarizes the main events of the HPV life cycle, the functions of the viral proteins, and the implications of HPV infection on their hosts, with an emphasis on carcinogenic mechanisms and disease outcomes in cervical and head-and-neck cancer.

Active surveillance for favorable-risk prostate cancer has become increasingly popular in populations in which prostate cancer screening is widespread because of evidence that screening results in the detection of disease that is not clinically significant in many patients. This Review discusses the results of active surveillance, the criteria for patient selection and the appropriate thresholds for intervention.

Primary tumor removal is usually considered as intrinsically beneficial, but this can perturb metastatic homeostasis and, for some patients, results in the acceleration of metastatic cancer. This Review analyzes the recent evolution of two paradigms related to the development of breast cancer metastases, and discusses the limitations of these paradigms in terms of how they explain breast cancer recurrence dynamics for patients undergoing surgery with or without adjuvant chemotherapy.

The pathogenic relationship between bisphosphonates and osteonecrosis of the jaw is unclear, but there is evidence to indicate an association between high-dose bisphosphonate treatment and exposure to dental infections and oral surgical procedures. The authors of this Review highlight that a better knowledge of the interactions between these agents and of the jaw and maxillary bone biology will improve clinical and therapeutic approaches to osteonecrosis of the jaw.

Techniques that combine the skills of resection with reconstruction have led to a third approach called oncoplastic breast-conserving reconstruction. Emerging data on the oncological and cosmetic outcomes of this technique confi rm the clinical utility of this new approach to the surgical management of patients with breast cancer, as discussed in this Review.

While many studies assessing the cost of cancer care have been conducted in the US, to date, these studies and the underlying methods used to estimate costs have not been reviewed systematically. The authors of this article conducted a descriptive review of the published literature on the cost of cancer care in the US, and discuss the implications of the heterogeneity of their findings.

The current choice for men with localized prostate cancer lies between active surveillance and radical therapy, but overtreatment associated with therapy poses a significant challenge. The authors of this Review propose a new concept whereby only the tumor focus and a margin of normal tissue are treated. The advantages and limitations of active surveillance and of radical therapy are reviewed, with focal therapy presented as a means for bridging these two approaches. With emerging techniques that can treat to millimeter accuracy, focal therapy of prostate cancer is now possible.

There is no standard treatment forBRCA1/2carriers with a new diagnosis of breast cancer. Personal and family-history-based criteria do not accurately predict the probability of a positive test result and thresholds for deciding who should be tested vary considerably among countries. The authors of this Review discuss how preventive and therapeutic approaches can be tailored to individuals by integrating the latest translational and clinical research findings. They also propose an individualized management algorithm on the basis of existing evidence, and discuss the challenges related to genetic testing, prevention and treatment strategies.

Population-based survival data can provide valuable comparative data on outcome but should be interpreted with caution. Ideally, data from the whole population, including clinical-only diagnoses, should be reported and the methods of case identification described. Erridge et al. highlight the need for methods of data collection and comparison to be as similar as possible, and for important factors related to the patient, tumor characteristics and treatment that might impact outcome to be reported.

The insulin-like growth factor 1 (IGF1) signaling pathway is implicated in the development of cancer. IGF1R signaling has been found to correlate with resistance to anti-EGFR and HER2-based therapies in experimental systems. This Review highlights the most relevant studies in this exciting area of research, focusing in particular on the role of the IGF1R in the resistance of other receptor-targeted therapies.

Despite recent advances in the field of medical and radiation oncology, and the introduction of neoadjuvant and adjuvant regimens, surgery remains the single most important modality for the treatment of pancreatic ductal adenocarcinoma. This Review discusses the technical improvements that have made pancreatic surgery safe, with low morbidity and mortality rates in tertiary referral centers, and it highlights the challenges of surgical palliation.

Emerging knowledge of the normal breast cell types has led to the hypothesis that the subtypes of breast cancer might arise from mutations or genetic rearrangements that occur in different populations of stem cells and progenitor cells. The authors of this Review describe the common distinguishing features of these breast cancer subtypes and explain how these relate both to prognosis and to selection of the most appropriate therapy.

The molecular mechanisms that underpin angiogenesis in breast cancer are becoming clearer, particularly in relation to hypoxia. Some established therapies including tamoxifen and trastuzumab might function, in part, by suppressing angiogenesis. The authors of this Review discuss the potential of components of the angiogenic pathway as prognostic and predictive factors in breast cancer, and comment on the challenges facing the clinical development and optimum use of these agents.

Surgery is the most frequently used approach in the treatment of nonmelanoma skin cancer, and Mohs micrographic surgery, conventional excision, cryosurgery, or electrodesiccation and curettage are usually performed. Newer noninvasive options include topical chemotherapeutics, biological immune-response modifiers, retinoids, and photodynamic therapy. Neville et al. propose that treatments should be tailored to the tumor type, location, size, and histological pattern, and suggest that, although surgical methods remain the most frequently used, newer noninvasive treatments can be used in select tumors and may reduce morbidity.

There have been considerable advances in our understanding of renal cell carcinoma, which have been translated into the development of several drugs with proven efficacy, with kinase inhibitors demonstrating significant activity. The authors of this review discuss the targeted agents that have proved efficacious in the difficult-to-treat metastatic setting, and highlight the issues of patient selection, scheduling, dose, duration of treatment, potential combinations and toxicity.

Confocal laser endomicroscopy is a new endoscopic tool that allowsin vivo histology at subcellular resolution during ongoing endoscopy, and permits subsurface imaging of normal and neoplastic human mucosa. The authors of this Review highlight why confocal laser endomicroscopy can no longer be regarded as just another endoscopic technique but emerges as a crucial novel imaging technique for in vivodiagnosis of colorectal cancer.