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Douglas Kondziolka, Hideyuki Kano, Gillian L. Harrison, Huai-che Yang, Donald N. Liew, Ajay Niranjan, Adam M. Brufsky, John C. Flickinger and L. Dade Lunsford

B rain metastases account for the majority of intracranial tumors, and breast cancer is second to lung cancer only as a common source of such tumors. 24 Brain metastasis, a significant cause of morbidity and death, ultimately develops in approximately 20%–40% of patients with cancer. 34 Reported incidences vary from 5% 5 , 30 to 10%–20% 13 in clinical series, to as high as 30% in autopsy studies. 35 Incidence appears to be increasing—most likely because of earlier diagnoses, better neuroimaging methods, and longer survival from the primary diagnosis. 34

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Praveen Deshmukh, Roberta P. Glick, Terry Lichtor, Risha Moser and Edward P. Cohen

T he current prognosis for patients with malignant brain tumors remains poor in spite of optimal treatment with current therapeutic modalities. 19, 29 Breast cancer is one of the most common malignant tumors that metastasize to the brain and is commonly the cause of death. Metastasis to the CNS occurs in 15 to 30% of patients with breast cancer, and despite the availability of surgery, radiotherapy, and chemotherapy, the 2-year survival rate remains dismal. New and innovative forms of effective treatments are urgently needed. One emerging strategy in the

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Sharad Goyal, Dheerendra Prasad, Frank Harrell Jr., Julie Matsumoto, Tyvin Rich and Ladislau Steiner

M ore than 240,000 new cases of breast cancer are diagnosed each year and one of every eight women will suffer from breast cancer in her lifetime. Breast cancer ranks second among deaths from cancer in women, with an estimated 41,000 deaths each year. Brain metastases from breast cancer occur in approximately 10% of patients, 2 a rate second only to lung metastases. The presence of intracranial lesions is considered an inauspicious prognostic indicator. Standard treatments for brain metastases include WBRT, chemotherapy, resection, and GKS. The untreated

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Cully A. Cobb III, Milam E. Leavens and Nylene Eckles

treatment of patients with spinal cord compression due to epidural breast cancer from a primarily operative approach to a primarily nonoperative approach. The patients who were initially operated on underwent emergency laminectomy and often received postoperative radiotherapy. The patients who were initially irradiated received emergency radiotherapy and only underwent laminectomy if they deteriorated during radiotherapy. In an effort to evaluate these two forms of treatment in a fairly homogeneous group of patients, we abstracted the charts of those patients who had

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Kenneth J. Levin, Emad F. Youssef, Andrew E. Sloan, Rajiv Patel, Rana K. Zabad and Lucia Zamorano

D espite adjuvant systemic treatment, almost 40% of patients with breast cancer will die of systemic disease. 1 This has led to a great interest in HDC and ABMT in patients with high risk and/or metastatic disease. The goal of this therapy has been improved longterm disease control and survival. The authors of randomized trials, however, have failed to show survival benefit for HDC/ABMT. 8, 11 In addition, studies have suggested an increased incidence of cognitive deficits in patients receiving HDC. 12 Whole-brain radiotherapy has been associated with

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Shireen Parsai, Jacob A. Miller, Aditya Juloori, Samuel T. Chao, Rupesh Kotecha, Alireza M. Mohammadi, Manmeet S. Ahluwalia, Erin S. Murphy, Gene H. Barnett, Michael A. Vogelbaum, Lilyana Angelov, David M. Peereboom and John H. Suh

M ore than 50% of all patients diagnosed with breast cancer brain metastases have human epidermal growth factor-2 receptor (HER2)-positive (HER2+) disease. 25 Over the past two decades, outcomes have improved for HER2+ patients with the advent of the HER2 receptor-targeted antibody trastuzumab, which has become a standard of care treatment option for this population. Trastuzumab has a high molecular weight and resultant poor penetration of the blood-brain barrier (BBB), leaving these patients at high risk for intracranial failure. 4 , 9 , 21 In fact, with

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Fatih Bayrakli, Bekir Akgun, Burcak Soylemez, Metin Kaplan and Mustafa Gurelik

(E) . In recording the family medical history of the patient, we learned that the patient's mother and her 3 sisters had died of early onset breast cancer, and the brother of the patient's mother had died from liver cancer ( Fig. 2A ). Mutational analysis of the BRCA1 and BRCA2 genes demonstrated a homozygous AAT to CAT (Asn372His) change in exon 5 of the BRCA2 gene in the 13-year-old boy, which was heterozygous in the father ( Fig. 2B ). This variant is known to be associated with breast cancer risk. 5 F ig . 2. A: Pedigree of the family with a

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Michael Mix, Rania Elmarzouky, Tracey O'Connor, Robert Plunkett and Dheerendra Prasad

B rain metastasis may occur in up to 30% of breast cancer cases. 22 Commonly used treatment options in this scenario include conventionally fractionated whole brain radiotherapy (WBRT), single- or multisession stereotactic radiosurgery (SRS, including Gamma Knife radiosurgery [GKRS]), tumor resection, or some combination of the above. The proper approach to breast cancer patients with brain metastases remains incompletely defined. With improvements in the management of both primary and metastatic disease over recent years, in particular with the use of targeted

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Patricia Zadnik, Rachel Sarabia-Estrada, Mari L. Groves, Camilo Molina, Christopher Jackson, Edward McCarthy, Ziya L. Gokaslan, Ali Bydon, Jean-Paul Wolinsky, Timothy F. Witham and Daniel M. Sciubba

metastatic breast cancer. Although multiple models exist, their utility is limited. First, many patients do not present with a single metastatic lesion. Furthermore, the mechanisms governing tumor seeding into bone are crucial components of the metastatic process, and direct implantation models eliminate the opportunity to study endogenous mechanisms of cancer spread. Of note, morbidity associated with the surgical approach to the anterior VB may also limit the animal's overall health and functional status. Finally, intracardiac injection with commercially available cell

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Jason Sheehan

In 2010, it is estimated that 207,090 women will be diagnosed with and 39,840 women will die of breast cancer. 1 The lifetime risk for breast cancer in a woman born today is 12.15%. As a result of earlier diagnosis, aggressive resection, and improvements in adjuvant treatment, most women with breast cancer tend to have extended survival relative to patients with other types of cancer. In fact, the 5-year survival for patients with breast cancer is 89%. Currently, more than 2.5 million women in the US have a history of breast cancer. Metastases to the CNS