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Fellow in Hematology Oncology, Taussig Cancer Institute, Cleveland Clinic, 2010 E 90th St, Cleveland, OH 44195, USA Director of Breast Oncology Program, Department of Hematology/Oncology, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA Professor of Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA *Author for correspondence: Tel.: +1 216 445 0150; Fax: +1 216 444 9464; abrahaj5@ccf.org In 2014, an estimated 232,760 women will be diagnosed with breast cancer (BC) in the USA, and approximately 40,000 will die from the disease [1]. The incidence of brain metastases (BM) from BC is approximately 5% [2,3], and the number increases to 10–16% among women with stage IV BC [4,5]. However, these figures still underestimated the disease burden, with up to 30% of BC patients found to have BM at autopsy [6,7]. Among breast cancer brain metastasis (BCBM) patients, parenchymal BM are more common than leptomeningeal involvement with the latter being reported about 5 to 16% of patients at autopsy [8]. Management of BCBM remains a clinically unmet need with few therapeutic options or clinical trials. Improvements in systemic treatment increased survival of BC patients, and unmasked a subpopulation with BM that may significantly impair patient’s life quality and survival. Unique challenges in managing BCBM patients lie in overcoming blood–brain barrier (BBB) and resistance to multiple lines of prior treatment since patients in this setting are typically pretreated [9]. Recently, better characterization of BCBM patients, development of new systemic therapy along with improvements in trial design and imaging modalities regenerated an interest in developing novel agents for BCBM patients.

ABSTRACT Until only a few years ago, there was only one truly effective therapy for patients with metastatic melanoma. While long-term remission could be achieved in some patients, toxicities associated with high-dose IL-2 were significant. New insight related to molecular pathways of tumor cells indicated that an activating mutation of BRAF can be found in approximately 50–60% of all patients with melanoma. Proof-of-concept demonstrated in clinical trials of a drug targeting mutant BRAF led to the approval of vemurafenib by the US FDA in August 2011. Supplied in an oral dosage form, we provide an alternative method of administering vemurafenib in a patient unable to take anything by mouth.

SUMMARY The US FDA approved eribulin as a third-line treatment for patients with metastatic breast cancer on 15 November 2010, based on the EMBRACE study. Eribulin has modified the management and enriched therapeutic options for patients with metastatic breast cancer. It has also improved life expectancy without increasing toxicity in this group of patients. In the future, this agent may achieve additional indications for treating malignancies other than breast cancer. This article summarizes data from various eribulin studies.

Jame Abraham speaks to Joanna Milburn, Commissioning Editor: Dr Jame Abraham is the first Bonnie Wells Wilson and Distinguished Professor and Eminent Scholar in Breast Cancer Research at West Virginia University. He did his Fellowship in Hematology/Oncology at the National Cancer Institute (NCI) and National Heart Lung and Blood Institute of the National Institutes of Health. He did his residency at the School of Medicine, University of Connecticut (CT, USA) and medical degree from Calicut Medical College in India. He is a member of the Breast Cancer Working Group of the National Surgical and Adjuvant Breast and Bowel Project (NSABP) and has served on the board of Directors for the South Atlantic Division of the American Cancer Society. He is the principal investigator of more than 15 clinical trials at the Mary Babb Randolph Cancer Center. His translational research is focused on understanding the pathophysiology of chemotherapy-induced cognitive dysfunction. His research group has made notable contributions in preclinical and clinical settings, as well as the genomic understanding of ‘chemo brain’. He was the Institutional principal investigator for the Eastern Cooperative Oncology Group (2003–2012) and NSABP clinical trials at West Virginia University (WV, USA). Jame is the founding editor of Bethesda Handbook of Clinical Oncology. Jame is the chief editor of the Emerging Cancer Therapeutics series published by Demos Publishing, New York (NY, USA). He is also the editor of Community Oncology Journal, Elsevier (NY, USA). He is on the Editorial Boards of several journals, including Community Oncology, Supportive Cancer Therapy, Oncology and Biotechnology News and Expert Review of Anticancer Therapy. Jame has received several awards, including an award from the President of India (Vaidya Bhooshan, 2010), Dean’s Award for Excellence in Clinical Medicine (2010), Outstanding Faculty Award (2007) and Clinician of the Year Award (2006) by the Department of Medicine, Idea Award and Career Development Award from the Department of Defense (2002), and Merit Award from the American Society of Clinical Oncology (2001).

SUMMARY The majority of patients with breast cancer are estrogen- and progesterone-receptor positive, and have benefited from the development of anti-estrogen therapies, such as tamoxifen and aromatase inhibitors. Unfortunately, metastatic patients will eventually develop resistance to these agents. Inhibitors of the mTOR, particularly everolimus, show promising activity in this group of patients. mTOR inhibition appears to reverse resistance to anti-estrogen therapy in the estrogen-receptor-/progesterone-receptor-positive subset. Additionally, they may have a similar effect by reversing anti-HER2 resistance in patients who overexpress HER2. This article reviews the mechanism of action of mTOR inhibitors and summarizes the available clinical data of their use in breast cancer.

Breast cancer is the most common cancer that affects women worldwide with an estimated 1.3 million new cases diagnosed annually [1]. The highest incidence remains in the developed world; however, incidence rates are steadily rising in other areas of the world. Between 2002 and 2020, breast cancer incidence and mortality are expected to rise 50%, with the greatest rise occurring in developing countries [2,3]. Several theories have been proposed to explain this rise in incidence, and most turn to the lifestyle changes that occur as countries become more westernized. For example, in India the most common cancer type among women is cervical; however, once these women migrate to the USA, breast cancer becomes the most common cancer [4]. Other studies evaluating breast cancer incidence in immigrants from lowresource or transitioning countries have shown similar changes [5–7]. Urbanization within countries demonstrates parallel increases; for example, there has been a 20–30% increase in breast cancer over the past decade in China’s urban registries [2,5]. This shift relates to better screening mechanisms, as well as diet and lifestyle changes. As areas become more developed, breast cancer risk factors such as obesity, early menarche and decreased or late childbearing are becoming more prevalent [4,5]. As these numbers continue to increase, it is important to remember the limited resources and different cultural beliefs in these areas and the importance of designing a unique and effective approach to decreasing the developing breast cancer burden. The main focus for low-income countries is often placed on communicable diseases; however, as these become more controlled, the population is living longer and cancer burden is becoming more significant. WHO projected that global deaths from infectious disease, maternal and perinatal disorders and nutritional deficiencies combined would decrease by 3% from 2005 to 2015, while noncommunicable diseases would increase by 17% [3]. In 1970 the proportion of all newly diagnosed cancers worldwide in the developing world was 15%, which is a contrast to the expected proportion of 70% in 2030 [8]. The General Assembly (United Nations) has acknowledged this growth as one of the major challenges facing development