Clinical Breast Cancer June 2005 • 115 Introduction Breast cancer frequently metastasizes to the brain. Over the past 50 years, autopsy series of breast cancer pa- tients have reported brain metastases in 6.7%-36% of se- lected patients. 1,2 Brain metastases can cause substantial neurologic deterioration or death. However, patients with brain metastases from breast cancer make up a heteroge- neous group. Even after developing brain metastases, some patients will live for a relatively long time, and many die as a result of progressive systemic, extracranial dis- ease. 3-5 In order to provide a framework for approaching these patients this article reviews retrospective studies that focus on patients with breast cancer and summarizes randomized trials of patients with brain metastases from multiple primary sites. Brain Metastases from Breast Cancer: Epidemiology Brain metastases are usually diagnosed after they cause neu- rologic symptoms such as headaches, focal weakness, impaired thinking, or seizures. In a population-based cohort from the Netherlands that was comprised of 802 patients with all stages of breast cancer, the cumulative incidence of symptomatic brain metastases at 5 years was 5% for all patients and 12.6% for pa- tients with stage IV disease. 6 When symptomatic brain metas- tases develop in the setting of aggressive chemotherapy for metastatic breast cancer (MBC), disease progression can be lim- ited to the central nervous system (CNS). For example, in a se- ries of 78 patients selected because of response to paclitaxel from 5 phase II clinical trials, 7 of the 52 patients (13.4%) with subsequent disease progression developed CNS metastases. 7 Remarkably, 6 of these patients had isolated CNS failures. Submitted: Mar 26, 2004; Revised: May 3, 2004; Accepted: May 3, 2004 Address for correspondence: Jay S. Loeffler, MD, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 100 Blossom St, Boston, MA 02114 Fax: 617-726-3603; e-mail: jloeffler@partners.org Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA Brain Metastases in Patients with Breast Cancer: New Horizons Brain metastases occur in as many as one third of patients with disseminated breast cancer. In this article, we discuss various presentations of brain metastases from breast cancer and review evidence that supports different treatment options. Because no prospective, randomized, controlled studies, to our knowledge, have focused solely on patients with brain metastases from breast cancer, we will first review retrospective studies of patients with brain metastases from breast cancer. Randomized studies of patients with brain metastases caused by multiple primary cancers will also be examined, and the conclusions from these studies will be extrapolated to patients with breast cancer. Because brain metastases from breast cancer occur in a variety of different clinical settings, ranging from a single metastasis without extensive extracra- nial disease to multiple brain metastases with widespread extracranial disease, treatment approaches must be tailored to the specific circumstances of each patient. For different clinical scenarios, neurosurgical re- section, radiosurgery, and/or whole-brain radiation therapy may be appropriate treatment options. For patients with brain metastases from breast cancer that overexpresses HER2/neu, trastuzumab could alter the natural history of the non–central nervous system (CNS) disease. Therefore, HER2 status could also in- fluence the treatment of brain metastases from breast cancer. Given the prevalence of brain metastases in patients with metastatic breast cancer in contemporary series, the rationale for clinical trials of CNS screen- ing and prophylactic cranial irradiation will be discussed. Clinical Breast Cancer, Vol. 6, No. 2, 115-124, 2005 Key words: Chemotherapy, Neurosurgical resection, Radiation therapy, Radiosurgery review Abstract comprehensive David G. Kirsch, Jay S. Loeffler Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1526-8209, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.