must read for all with/anxious about brain mets

[Lani]

the "hot off the press" edition of Clinical Research has a series of articles on brain mets from her2+ breast cancer. I am lousy at links, but will try to place some here:


http://clincancerres.aacrjournals.org/cgi/reprint/13/6/

unable to link the following, but here are abstracts:

1: Clin Cancer Res. 2007 Mar 15;13(6):1644-7.
CNS metastasis: an old problem in a new guise.

Aragon-Ching JB,
Zujewski JA.
Authors' Affiliation: Center for Cancer Research and Division of Cancer Therapy Diagnosis and Treatment, National Cancer Institute, Bethesda, Maryland.
It is estimated that 10% to 30% of patients with solid tumors are diagnosed with central nervous system (CNS) metastasis. Common primary sites include lung, breast, melanoma, kidney, and colorectal. Brain metastases are increasing, due to the aging population, detection of subclinical disease, and control of systemic disease. CNS metastases are a major cause of morbidity and mortality affecting survival, neurocognition, speech, coordination, behavior, and quality of life. In pediatric acute lymphocytic leukemia event-free survival rates are >80% and the CNS is an important source of extramedullary relapse. CNS metastases are an increasing problem in solid tumors. In this CCR Focus series, four main topics are reviewed: (a) HER-2-positive breast cancer as a paradigm for the problem; (b) model systems for brain metastasis and mechanistic insights into the pathogenesis of brain metastasis; (c) the unique physiology of the blood brain barrier; (d) and the evolving role of radiotherapy in CNS disease and strategies to improve the therapeutic index. Areas for future research include the need for an understanding of site-specific metastasis, effective anticancer strategies for sanctuary sites, assays to detect drug accumulation in sanctuary sites, prevention of CNS metastasis, improving the therapeutic ratio of systemic and CNS-directed therapies, behavioral tools for anticipating/measuring long-term neurocognitive defects, and quality of life assessment of the long-term effect of systemic and CNS-directed therapies.
PMID: 17363516 [PubMed - in process]

Brain Metastases: The HER2 Paradigm

Nancy U. Lin and Eric P. Winer
Author's Affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts

Requests for reprints: Eric P. Winer, Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115. Phone: 617-632-6876; Fax: 617-632-1930; E-mail: ewiner@partners.org.

Abstract

Between 100,000 and 170,000 patients with cancer develop central nervous system (CNS) metastases each year in the U.S., of which 20% carry a primary diagnosis of breast cancer. As a consequence of improvements in systemic therapy, which have allowed patients to live longer with advanced cancer, CNS metastases are emerging as an important sanctuary site, and the incidence may be increasing in patients with particular tumor subtypes. Unless there are improvements in the treatment of CNS disease, a growing proportion of patients may be at risk of experiencing both morbidity and mortality as a result of uncontrolled CNS progression, often at a time when their extra-CNS disease is apparently under control. This article reviews changes in the epidemiology and natural history of women with brain metastases from HER2-positive breast cancer over the last decade and presents the therapeutic challenges and opportunities that have arisen in this setting. First, the apparent increase in CNS disease among women with HER2-positive breast cancer, relative to historical controls, is discussed, followed by consideration of potential causes of this observation. Next, the implications of CNS disease, in terms of prognosis and the potential development of preventive strategies are considered. Finally, new developments in systemic approaches to the treatment of CNS disease, including cytotoxic chemotherapy and targeted therapy, are explored.



Targeted Therapy for Brain Metastases: Improving the Therapeutic Ratio

Rakesh R. Patel and Minesh P. Mehta
Authors' Affiliation: Department of Human Oncology, University of Wisconsin, Madison, Wisconsin

Requests for reprints: Rakesh R. Patel, Department of Human Oncology, University of Wisconsin, 600 Highland Avenue, K4/B100, Madison, WI 53792. Phone: 608-263-8500; Fax: 608-263-9167; E-mail: patel@humonc.wisc.edu.

Abstract

Brain metastasis is the most common intracranial malignancy in adults. Improvements in modern imaging techniques are detecting previously occult brain metastases, and more effective therapies are extending the survival of patients with invasive cancer who have historically died from extracranial disease before developing brain metastasis. This combination of factors along with increased life expectancy has led to the increased diagnosis of brain metastases. Conventional treatment has been whole brain radiotherapy, which can improve symptoms, but potentially results in neurocognitive deficits. Several strategies to improve the therapeutic ratio are currently under investigation to either enhance the radiation effect, thereby preventing tumor recurrence or progression as well as reducing collateral treatment-related brain injury. In this review article, we discuss new directions in the management of brain metastases, including the role of chemical modifiers, novel systemic agents, and the management and prevention of neurocognitive deficits.

there are about three more--go to www.aacr.org, to journals and click on clinical cancer research and choose the march 15 issue

Don't worry--it is not ALL scary and it shows they are now really working to understand how to improve treatment, detect and prevent brain mets