This study will examine a non-invasive method to assess vasculature, that is, the
development of a blood supply necessary to the growth of tumors. The hope is to identify
the way that genes are expressed within the tumor itself, from areas shown as low flow
versus those shown as high flow on dynamic contrast-enhanced magnetic resonance imaging
Most patients with solid epithelial cancers, those that develop on free surfaces or linings
inside the body, die because of the distant spread of tumors-metastasis. After that spread,
a cure is more difficult than if the tumors were detected early or locally. Tumors develop
a new supply of blood. Traditional anticancer therapies have had the goal of causing a
decline in the tumor. Yet by focusing on the tumor's blood supply, microscopic differences
between tumors and clonal differences within tumors may be avoided. Doing so may overcome
tumor resistance to treatment and may result in treatments that can be more universally
applied across tumor types.
Female patients 18 years of age enrolled in the protocol Analysis of Brain Metastasis in
Patients with Breast Cancer, with and without Over-Expression of HER-2, who will undergo an
MRI scan immediately before surgery will be invited to participate in this study. Patients
seen in the oncology outpatient clinic of the NIH Clinical Center or by referral from
outside physicians may be eligible for this study.
Participants will undergo DCE-MRI immediately before the craniotomy-the surgery scheduled-in
conjunction with other clinically indicated MRI. The preoperative MRI will take about 30
minutes, and the DCE-MRI will take no more than 15 minutes. During the MRI, patients will
lie still on a table that can slide in and out of a metal cylinder surrounded by a strong
magnetic field. They may be asked to lie still for up to 5 minutes at a time. As the
scanner takes pictures, there will be loud knocking noises, and the patients will wear
earplugs to muffle the sound. Patients will be able to communicate with the MRI staff at
all times during the scan and may ask to be moved out of the machine at any time. During
part of the MRI, patients will receive a contrast agent, one that is gadolinium-based, into
a vein. This agent changes the relative brightness or contrast on the MRI image under some
conditions. Before that agent is used, patients will be asked about any previous allergic
reactions to gadolinium-based contrast agents.
Introduction: Metastasis of epithelial tumors, such as breast cancer, to the brain is a
common problem, with significant consequences with respect to neurological dysfunction and
shortening of survival. One necessary step for tumor growth anywhere is the development of
a blood supply.
Objectives: We seek to compare a new, non-invasive method of assessing neo-vascularization,
dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a
gold-standard-microvessel counts-and to see if we can identify gene expression patterns
within the tumor itself, from areas shown as low flow versus those that are high-flow on
DCE-MRI if there are features within the tumor itself that influence the degree of
neovascularization. This prospective study will only be utilized in conjunction the
protocol entitled "Analysis of Brain Metastasis in Patients with Breast Cancer, with and
without over-expression of HER-2" that is evaluating breast tumors metastatic to the brain.
Study Population: A series of women with breast cancer metastatic to the brain who do
(n=39) or do not (n=39) over-express the growth factor receptor, HER-2, entered into a
prospective trial in which pre-operative MRI imaging is performed as a matter of standard
medical practice. At the time of this pre-operative MR, we propose to add one additional,
10-minute MR series, a dynamic, contrast-enhance image to assess the extent of blood flow
through various aspects of the tumor.
Anticipated Risks and Benefits: There are no obvious risks or benefits to patients who
participate in this protocol. It is felt that this study involves no more than minimal risk.
Estimation of Outcome/Potential Meaning: We believe that this protocol will help us
identify tumors with higher or lower degrees of neovascularization as well as identify
tumor-intrinsic factors via microarrays performed on microdissected tissues. This is
becoming an important issues as cytostatic treatments, such as anti-angiogenic agents, enter
the clinical area, and are used singly or in combination with cytotoxic therapies.
1. A woman with a known or with radiographic evidence of a breast neoplasm metastatic to
the brain, who has agreed to participate in the protocol "Analysis of Brain
Metastasis in Patients with Breast Cancer, with and without over-expression of
HER-2," and who will undergo a pre-operative MR scan immediately before surgery.
2. Medically-indicated (diagnostic and/or therapeutic) brain tumor resection.
3. Informed consent from female patient, age 18 or older. In general, patients less
than 18 years of age rarely have breast cancer metastatic to the brain.
1. Inability to provide informed consent prior to surgery.
2. Medical conditions that cannot be corrected prior to surgery that would be standard
contraindications for craniotomy (brain tumor patients).
3. Conditions that preclude MR imaging of the brain (Patients with pacemakers, cerebral
aneurysm clips, shrapnel injury or implantable electronic devices) or known allergy