In order to minimize these risks the following precautions will be taken: 
Procedures (phlebotomy, lumbar puncture, infusions, etc.) will be performed in the hospital. 
Risks of scans will be minimized by careful questioning whether patients have metal clips, foreign bodies, 
etc. Risks of gene therapy will be minimized by the use of replication-incompetent viral vectors which 
express anti -proliferative genes. Tests are performed to verify that all lots of retroviral vector do not 
contain any contaminating replication-competent virus. The vectors are designed to be expressed only in 
breast cells, and will produce only anti -oncogenes (which have previously been shown to act as anti- 
proliferative signals in non-malignant cells). Our preclinical data suggests that the spread of the virus is 
quite limited under these conditions. To minimize the chance of transmission of infectious agents, tests to 
identify mycoplasma, bacteria, and replication-competent retroviruses will be performed on lots of 
retroviral vector in accordance with standards set by RAC and by the FDA. 
Risk: benefit ratio 
The expected course for patients with metastatic breast cancer with malignant effusions is 
progressive with no hope for cure. The benefits from the proposed therapy are the potential reversal of the 
malignant effusions with prolongation and improvement in the quality of life. Possible significant toxicity 
from the proposed therapy includes the risks of paracentesis, thoracentesis, or lumbar puncture: 
hemorrhage, viscus perforation, and infection. Removal or infusion of fluid can result in allergic reaction, 
fluid imbalance, heart failure, or electrolite abnormalities. The probability and magnitude of potential 
adverse effects from this proposed therapy are rare and relatively minor compared with the patient's fatal 
malignancy. The probability of success of this clinical protocol can not be predicted but it would represent 
an important therapy if the results in humans mirror the results obtained in preclinical animal studies. 
6. Confidentiality and Public Disclosure 
Confidentiality will be maintained at all times and patient identity will not be disclosed. 
Publications will refer to patients by number and not by initials or other shorthand which allow linkage to 
individual patients. Recores will be encoded so that confidentiality is maintained.The identity of patients 
who participate in the study will not be publicly disclosed. 
Individual discussions with the patient and family members will be scheduled to answer all 
concerns and questions about the protocol. Co-P.I. Dr. Carlos Arteaga is a board-certified oncologist and 
basic scientist who has tprior experience in discussing clinical protocols with cancer patients and their 
families. Basically patients will be informed in lay terms of the results with human tumor lines in the 
laboratory emphasizing the tumor selective nature of the genetic treatment and the potential advantages it 
may have over "conventional" anticancer drugs. The latter are costly, not very likely to work in patients at 
this stage, and for sure toxic to host tissues. On the other hand, our therapy does not prevent them from 
receiving these alternative therapies immediately after studies are completed. 
Issues of cost are clearly outlined in the consent form. There will be no cost to the patient for the 
protocol studies conducted in the clinical research unit, or for the followup studies which are part of the 
protocol. 
The goal of these studies is to gain information which should lead to more efficient gene transfer 
without malignant effusions.. All information gained will be available to the research community and to the 
public. 
Recombinant DNA Research, Volume 20 
[175] 
