Date: Mon, 8 Jan 2001 14:51:17 -0600 (CST)

Diana Zuckerman Via Myrl 

Dear Myrl,

In response to your concerns about polyurethane covered implants, here are the relevant sections from the Congressional report that I wrote in 1992. The entire report is linked to our website (the last document listed on our breast implant section) but I have printed it below for your convenience. Feel free to share with whoever you think might find it of interest. 

Diana Zuckerman 

POLYURETHANE, TDA, AND CANCER 

By March 1990, an FDA pharmacologist had written an internal memorandum expressing concerns that there could be a cancer risk associated with silicone breast implants that were covered with polyurethane foam. The foam is similar to that used for chair cushions or filters for air conditioners. These implants were sold by Surgitek, a subsidiary of Bristol-Myers Squibb; the most popular model was called "the Même". The March 1990 memorandum reviewed the previous evaluations of foam degradation from polyurethane covered implants. This included adverse reaction reports dating from 1984-1988 indicating that the foam came off the implant or broke down into fragments, or was "partially digested". By 1986, there were two reports of foam from implants that "disappears". Based on 1989 and 1990 studies conducted for Surgitek on the breakdown of foam into 2,4 toluenediamine (TDA), a known animal carcinogen, the FDA pharmacologist estimated that the lifetime cancer risk would range from 6 in 1 million to 130-180 in 1 million.On April 10, 1990, Dr. James Dillon, a research chemist from FDA's Office of Science and Technology, wrote a memorandum to Hoan My Do Luu, the FDA pharmacologist, which stated, "Based on a review of inhouse documents, extramural research, case reports, and research proposals concerning the polyurethane foam used to manufacture the Natural Y Mammary Prosthesis, I conclude that this material presents an unreasonable risk when used as a degradable (intentional or otherwise) coating on the device." Dr. Dillon supported Ms. Luu's proposal to conduct a pharmacokinetics study to determine the levels of TDA resulting from breakdown of the foam in conditions similar to those found in the human body. 

C. FDA DELAYS AND INACTION 

The major delay in the regulation of breast implants occurred between the 1982 publication of the proposed rule classifying implants as Class III devices, and the publication of the final rule in June 1988. However, after the final rule was published, the 30-month wait for PMA's could have ended in December 1990.In late 1988, the Acting Director of FDA's Office of Device Evaluation stated that FDA would move quickly to regulate breast implants, and would require PMA's by the end of 1990. Instead, the proposed regulations were issued in-May 1990, the comment period ended in August 1990, and the final regulations were not published until April 1991.

D. IMPLANT PATIENTS AS GUINEA PIGS 

There has been a considerable amount of research on breast implants, much of it published in plastic surgery medical journals. A subcommittee review of research published between 1970-1990 indicates a pattern of small studies, bias, and use of patients as guinea pigs in research. A good example has been the research regarding capsular contracture. A subcommittee review of 20 major articles dating from the early 1970's to the late 1980's indicated that many articles were written to describe efforts by plastic surgeons to reduce capsular contracture problems by using different implants or surgical techniques. Every few years, there was a new discovery, usually accompanied by concerns expressed about the problems of doing things the "old way". For example, silicone implants with dacron patches were very popular in the early 1970's; then the researchers reported that the dacron disintegrated or caused severe contracture problems. Implants with dacron patches were therefore criticized in the journal articles, and implants that did not have dacron patches were praised as preferable. Similarly, one favored surgical technique was replaced by another technique. In article after article, the old model or old technique was associated with between 50-75 percent serious contracture problems, and the new model or new technique reduced that to approximately 30 percent serious contracture problems. However, every few years, each "new way" was discredited when the proportion of long-term problems for that model or technique increased. The short-term success of the new technique would therefore make the new way seem superior. Since many of the articles were written by surgeons about their patients, it is not surprising that virtually all articles heralded some major improvement discovered by the surgeon.  

One of the "new" products that was promoted in journal articles was the polyurethane-covered silicone breast implant, which was designed to prevent capsular contracture. Early short-term studies indicated that patients had fewer contracture problems with these implants; however, by 1990 Canadian scientists were reporting that when polyurethane broke down in the body, "it cannot be completely removed without disfiguring surgery". In addition, as discussed earlier in this report, by 1990 there were reports of potential cancer risk caused by the polyurethane covering breaking down into TDA in the body. 

H. FDA CONCERNS ABOUT CANCER LED TO THE REMOVAL OF BREAST IMPLANTS COVERED WITH POLYURETHANE FROM THE MARKET IN 1991  

Silicone breast implants covered with polyurethane foam had been manufactured by several different companies since 1971. They became popular in the late 1980's, when they were made by Cooper Surgical. In 1986 and 1988, FDA inspectors reported that the implants were made under nonsterile conditions; for example, company employees blew into the implants to test for inflation. In December 1988, Cooper Surgical sold the breast implant business to Surgitek, a subsidiary of Bristol-Myers Squibb. By 1990, the Canadian Department of National Health was debating the cancer risks and other problems associated with silicone breast implants covered with polyurethane. At the subcommittee hearing in December 1990, an FDA scientist made the first public statement that FDA research indicated that the polyurethane that covers implants breaks down in the body to form a known animal carcinogen, TDA. 

By March 1991, an FDA scientist warned the Director of the Division of Compliance that Surgitek had terminated a study that may have indicated a cancer risk from the polyurethane foam. In April 1991, FDA scientists were estimating the cancer risk as between .5 and 100 per million patients. The 100 per million was based on total degradation of two breast implants; however, some plastic surgeons were recommending the use of two polyurethane implants stacked together on each breast. This would result in an estimate of 200 cancer patients per million.  

By May 1991, a scientist from Aegis Analytic Laboratory in Nashville contacted the FDA to inform them of a study of breast milk in an implant patient, which they had conducted at Surgitek's request. The scientist had informed the company that TDA had been found in the breast milk of a woman with polyurethane-covered implants, and he was concerned that the company was not making the information available to FDA or the public. Company officials argued that the laboratory finding was inaccurate, although the manufacturer had hired the lab to do the testing, and a third party retained by Surgitek had confirmed that the laboratory methods were appropriate and accurate. 

A month earlier, on April 10, 1991, FDA had published its final rule regarding the July 9 deadline for submitting proof of safety and effectiveness. There was extensive media coverage of the potential risks of TDA from breakdown of the polyurethane foam, and FDA officials were repeatedly questioned about their cancer risk estimates.  

As a result of these concerns, FDA informed Bristol-Myers Squibb that they would need additional data on the potential risks of TDA from the. polyurethane, in addition to the safety data on silicone required by the other manufacturers. As a result, Surgitek temporarily withdrew its implants from the market, and later announced that it would shut down all manufacture of breast implants permanently. Approximately 200,000-400,000 American women are estimated to have had polyurethane-covered implants; most were implanted between 1985-1990. 

FDA announced in April 1991 that they would require Bristol-Myers Squibb to conduct postmarket surveillance on the risks of their product, whether or not they intended to resume sales in the future. However, as of December 1992, more than 20 months later, the company had not provided any research data to FDA. 

The company's apparent lack of research on the carcinogenic risks of their product is in sharp contrast to their interest in the psychological health of women with breast implants. In response to the 1990 public comment period for the proposed rule on breast implants, Bristol-Myers Squibb quoted research indicating that small-breasted women who did not want breast implants expressed attitudes that supports women's rights; the company interpreted this as indicating that they were more "deviant" than small-breasted women who wanted breast implants. 

Later Section on FDA misleading the public: 

In April 1991, the FDA distributed a Talk Paper to explain that polyurethane-covered implants would no longer be available. The Talk Paper stated that polyurethane implants were voluntarily removed from the market, which ignored the fact that the FDA pressured Bristol-Meyers Squibb to "voluntarily" remove them due to concern about cancer risks. The FDA did not mention that the polyurethane had been found to be Scott Industrial Foam, a product made for automobile air filters and carpet-cleaning equipment and never intended to be implanted in the human body. 

The April 1991 Talk Paper also said that the polyurethane from the implants breaks down to TDA, which "has been linked to cancer in laboratory animals". That sounds less ominous than the more accurate explanation, which is that FDA has categorized TDA as an animal carcinogen and potential human carcinogen, as have the National Toxicology Program and the International Agency for Research on Cancer.--------------

Diana Zuckerman, Ph.D.

Executive Director

National Center for Policy Research for Women and Families 1444 Eye

Street, NW

Suite 900

Washington, DC 20005