Recombinant DNA Advisory Committee - 03/1-2/93 
of involvement is unclear. How effectively will tumor cells be removed by the CD34( + ) 
selection process? If tumor cells fail to be removed by the selection procedures, will 
they survive the in vitro culture conditions and inadvertently become transduced? These 
questions must be satisfactorily answered before patients can be allowed to participate in 
this protocol. 
Other Comments 
Dr. Brinckerhoff agreed with Dr. Krogstad's concerns about the possible transduction of 
tumor cells which would render them resistant to chemotherapy. There are no 
techniques available at the present time that can detect breast cancer cells that may 
contaminate the bone marrow. 
Ms. Meyers stated that she has several concerns about the informed consent document. 
All references that gene therapy or gene transfer is safer should be deleted. Gene 
therapy is still in its very early stages, and all possible outcomes are not yet known. The 
statement, 'Taxol is a new drug which has been shown to be effective in the treatment of 
breast cancer" should be deleted. Taxol has been approved for the treatment of ovarian 
cancer, but it is still considered experimental in the treatment of breast cancer. Patients 
should not be responsible for the experimental costs either personally or through their 
insurance. This procedure is very experimental, not only the gene therapy portion, but 
also the bone marrow transplantation procedure. The informed consent document 
should include a statement recommending that the patient should not be pregnant or 
planning to become pregnant. A statement should be included about a request for 
autopsy. The investigators should explain how they would respond to patients who might 
request this treatment on a compassionate use basis. 
Dr. Parkman said that he had requested that the informed consent document be revised 
in his written comments to the investigators and was disappointed that the revised 
document was not submitted. With regard to the issue of contaminating breast cancer 
cells in the bone marrow, this issue has been previously discussed during the review of 
Dr. Joyce O'Shaughnessy's protocol at the December 1992 RAC meeting. During the 
December 1992 meeting, Dr. Cynthia Dunbar stated that the majority of breast cancer 
cells are already MDR positive, and that data from other laboratories has demonstrated 
that there is a significant reduction in the number of breast cancer cells after CD34( + ) 
selection. The discussion should not focus on concerns of transducing non-MDR 
expressing tumor cells, but only on the possibility of over-expression of the gene. The 
CD34( + ) selection procedure reduces the total number of cells that are to be 
transduced, therefore, reducing the relative proportion of contaminating breast cancer 
cells. Dr. Brian Sorrentino, a co-investigator on Dr. O'Shaughnessy's protocol agreed 
with the comments made by Dr. Parkman. Dr. Sorrentino noted that one of the 
differences between the two protocols is that Dr. O'Shaughnessy's protocol included a 
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