Reviews & Analysis

The recently updated breast cancer screening guidelines from the American Cancer Society are less aggressive than previous versions and clearer about overdiagnosis. However, a lack of attention was placed on the differences in effect estimates between trials at high and low risk of bias, and the authors failed to quantify the most serious harm.

Lung-cancer treatment paradigms continue to advance as we exploit our growing understanding of the genetic basis of both tumorigenesis and therapy resistance. Moreover, ongoing developments with targeted therapies are improving patient outcomes, with two new drugs approved in 2015 for non-small-cell lung cancer and many others showing promise.

Advances in key areas of research have enabled improved outcomes for patients diagnosed with ovarian cancer in the past three decades. In 2015, this trend was maintained with important progress in areas such as guideline compliance, design of targeted approaches and molecular profiling.

In 2015, published trials highlighted the remarkable efficacy of docetaxel combined with androgen-deprivation therapy in patients with newly diagnosed metastatic prostate cancer. Also in 2015, a large study revealing potential molecular targets for metastatic castration-resistant prostate cancer therapies was published, along with a study showing activity of PARP inhibition in patients harbouring mutations in genes governing DNA repair.

A meaningful revolution in managing malignant diseases has occurred since the advent of molecular targeted therapies; while some agents have resulted in a clinical benefit, these novel agents are also associated with undesired effects and assessing these risks in the correct context of potential clinical benefit is paramount. The authors overview of the development and toxicity profiles of kinase inhibitors and monoclonal antibodies, with an emphasis on their clinical management, including patient supportive care needs, and the impact of these treatments use on the health-care expenditures at the end of life.

In a little over the past year, several clinical trials have evaluated new drugs in patients with metastatic colorectal cancer and gastric cancer. Furthermore, genomics studies that attempted to unravel the molecular characteristics of colorectal and gastric cancer were published in 2015. The results of these endeavours will influence clinical practice in 2016 and beyond.

Henderson and colleagues previously highlighted the need for more-rigorous standards of preclinical experimental design and reporting metrics. They now build on their earlier work with a meta-analysis of preclinical experiments that examined the efficacy of sunitinib. Their results demonstrate how suboptimal preclinical study designs can prompt unwarranted clinical expectations.

The presence of tumour-infiltrating lymphocytes (TILs) in breast tumours is related to a better prognosis in patients with early stage breast cancer, but the immunobiology of breast cancer remains to be well-characterized. In this Review, the authors discuss how to measure TIL-related parameters in the clinic, as well as their value as a prognostic and predictive biomarker in breast cancer. The rationale for enhancing immunity in breast cancer is also examined.

Acute myeloid leukaemia (AML) is a heterogeneous disease that is typically associated with a very poor prognosis; however, cytogenetic and molecular abnormalities that characterize different forms of AML have been used to better prognosticate patients and inform treatment strategies, which might enable better outcomes to be achieved. Moreover, in the era of next-generation sequencing and molecularly targeted therapy, genetic profiling of patients with AML could open new avenues of treatment. Herein, the authors discuss the evidence-base for integrating mutational data into treatment decisions for patients with AML, and propose novel therapeutic algorithms aimed at improving outcomes of this dismal disease by promoting clinical research.

Surgeons should promote the best standard of surgical care through evidence-based results from prospective trials. European surgical investigators, in this issue of the journal, highlight the difficulties in patient accrual to surgical trials, patient and physician biases, and referral and quality assurance hurdles. We expand on these points and suggest some solutions.

The practice of palliative care for patients with cancer is continually improving, and an increasing evidence base indicates that early integration of oncological and palliative care can result in wide-ranging benefits for the patients, their loved ones, clinicians, and health-care payers. Herein, David Hui and Eduardo Bruera discuss optimization of clinical infrastructures, processes, and education to support this strategy, and provide a conceptual model for the integration of supportive and/or palliative care with primary and oncological care. The authors emphasize the need for health-care systems and institutions to tailor integration based on their resources, size, and the level of primary palliative care available.

Use of radiotherapy or chemotherapy generally increases the survival of women with breast cancer; however, the use of radiotherapy, chemotherapy agents, such as the anthracycline doxorubicin, or anti-HER2 agents, such as trastuzumab, confer an increased risk of adverse cardiovascular events in these patients. In this Review, the authors describe the incidence and management of treatment-induced cardiac disease in women with breast cancer, and highlight strategies that might be used to minimize this risk.

Tumour cells can evade the immune response through different strategies, with the tumour microenvironment being a key determinant of which pathways become activated to restrain antitumour immunity. The authors of this Review describe the four major types of therapeutic interventions required in combinations to generate a strong antitumour response. Importantly, they also discuss which combination therapies might effectively engage immunity to suppress tumour progression in four different scenarios defined by the composition of the immune tumour microenvironment.

As the numbers of available anticancer drugs and thus possible drug combinations continues to grow, determining the optimal toxicity–efficacy balance of treatment regimens becomes increasingly complex, and the utility of standard empirical approaches to optimizing drug dosing and scheduling is becoming increasingly limited. Mathematical modelling can substantially advance the development of effective treatment regimens through improved rationalization of therapeutic strategies. In this Review, the authors highlight the achievements that have been made to date in computational modelling of drug regimens, as well as the limitations of this approach. They also discuss the potential future implementation of this strategy to achieve precision medicine in oncology.

Chromosome instability (CIN) is gaining increasing interest as a central process in cancer, and is indicated whenever tumour cells harbour an abnormal quantity of DNA, termed 'aneuploidy'. In this Review, the authors review the literature published since 2000 that support the hypothesis that aneuploidy is a predictor of a poor prognosis in patients with cancer, focusing on the evidence from studies of seven common epithelial cancer types that performed multivariate analyses. The implications of ploidy analysis with regard to our theoretical understanding of the role of CIN in carcinogenesis, as well as its prognostic use in the clinic, are discussed.

The results of three recent studies demand that more attention be placed on defining the most-appropriate approach to population-based breast-cancer screening, in particular regarding the potential harms of increasing overdiagnosis. Two of these studies report that more-sensitive detection of breast neoplasms is possible by 3D tomography and by MRI, but the third paper raises the question of whether this increased sensitivity is desirable.

Haematopoetic stem-cell transplantation (HSCT), has been the standard-of-care for eligible patients with chronic myeloid leukaemia (CML) for several decades. The development of tyrosine kinase inhibitors (TKIs) 15 years ago revolutionized the treatment of CML. For some patients, however, allogeneic HSCT remains the best treatment option. The authors of this Review discuss the current status of HSCT as a therapeutic option for CML management.

Cachexia, a syndrome where metabolic demands cannot be met by energy intake, can substantially reduce the quality of life and increase mortality of patients with oesophageal cancer. In this Review, authors describe the causes, and effects of cachexia in these patients throughout the disease trajectory, and during the survivorship period; suggestions are made on how best to manage the effects of, and minimize the occurrence of this syndrome.

A study assessing the impact of the 21-gene recurrence score assay in routine clinical practice on the use of adjuvant chemotherapy in women with early stage ER-positive breast cancers showed that adjuvant chemotherapy use decreased in high-risk patients, but increased in low-risk patients. I discuss these results and highlight how this reflects more-selective administration of chemotherapy.

In the RADIANT study, no difference in disease-free survival was observed for patients with non-small-cell lung cancer (NSCLC) treated with erlotinib versus placebo in the adjuvant setting. Further biomarker studies are awaited to determine whether patients with NSCLC can benefit from adjuvant therapy with tyrosine kinase inhibitors.