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U.S. Food and Drug Administration |
This article originally appeared in the November 1995 FDA Consumer and contains revisions made in March 1997. The article is no longer being updated. For current information on this topic, see "Breast Implant Information" on this Website. |
Recently published studies have shown that women with silicone gel-filled breast implants do not have a greatly increased risk of some well-defined autoimmune diseases, which were among the serious health concerns surrounding the devices. These include potentially fatal connective tissue diseases such as scleroderma and lupus erythematosus.
The new studies do not, however, rule out the possibility that a subset of women with implants may have a small increased risk of these conditions, or that some women might develop other immune-related symptoms that don't conform to "classic" disease descriptions.
Nor did the studies address other important safety questions, including implant rupture rates and the incidence of capsular contracture (shrinking of scar tissue around the implant, which can cause painful hardening of the breast or distort its appearance). Answers to these and other questions await the results of new or ongoing studies.
Widespread reports of adverse reactions to silicone gel-filled implants and a lack of evidence supporting their safety led the Food and Drug Administration to order the devices off the market in April 1992. They remained available only to women in clinical studies, mostly women seeking breast reconstruction after breast cancer surgery. Saline-filled implants were allowed to remain on the market for all uses.
Reasons for New Studies
Breast implants had been marketed since the early 1960s--several years before the first medical device law was enacted in 1976, charging FDA with regulation of medical devices. Every year, thousands of American women had implant surgery for augmentation (to enlarge or reshape their breasts) or for reconstruction following mastectomy (removal of the breast) to treat breast cancer. Most of the implants consisted of a rubber silicone envelope filled with silicone gel; about 10 percent were filled with saline (salt water).
Silicone gel-filled breast implants (a 52K JPEG file)
Saline-filled breast implants (a 42K JPEG file)
Under the 1976 law, implants and many other devices already in use were allowed to remain on the market, with the understanding that the agency would at some time ask manufacturers to submit scientific data showing these "grandfathered" products were safe and effective.
FDA requested this information for silicone gel-filled implants in April 1991 in response to a growing number of adverse reaction reports that raised safety concerns about the devices. The data submitted did not prove the devices safe, as required by law, so the agency restricted their use to clinical trials designed to resolve the safety questions.
Between Jan. 1, 1985, and Sept. 17, 1996, FDA received 103,343 adverse reaction reports associated with silicone breast implants and 23,454 reports involving the saline implants. Because these figures come from all databases, there may be a few duplicate reports. The reports included risks clearly associated with the devices, as well as adverse effects attributed to the implants, but not proved to be linked to them. (See "Known Risks of Breast Implants" and "Possible Risks of Breast Implants.")
Silicone Implant Studies
Some recent studies comparing the rates of immune-related diseases in women with implants versus those without implants have provided reassurance that women with implants are not at a greatly increased risk of these disorders.
The largest of these retrospective, or "look-back," studies is the Harvard Nurses' Health Study. The study used data from 87,501 nurses followed for other research purposes from 1976 through May 31, 1990, before there was widespread media coverage of the possible association between breast implants and connective tissue disease. None of the women had connective tissue disease at the start of the study.
In an article published in the June 22, 1995, New England Journal of Medicine, the researchers reported that 516 of the nurses had developed definite connective tissue diseases. Women with breast implants numbered 1,183. The types of implants included 876 silicone gel-filled, 170 saline-filled, 67 double lumen (silicone gel-filled implants with a saline-filled outer envelope), 14 polyurethane-coated, and 56 of unknown type. Only three of the 516 women with definite connective tissue diseases had implants (one silicone-gel filled, one saline, and one double lumen).
The authors reported they "did not find an association between silicone breast implants and connective tissue disease, defined according to a variety of standardized criteria, or signs and symptoms of these diseases."
Similarly, a 1994 study conducted at the Mayo Clinic found no increased risk of connective tissue diseases among implant recipients. The investigators based their conclusion on comparison of the medical histories of 749 women with breast implants in Olmsted County, Minn., with a similar group of women who did not have implants.
"Because of the limitations in the size and type of the studies, however, the true risk of these diseases is not known," says S. Lori Brown, Ph.D., a research scientist officer in the epidemiology branch of FDA's Center for Devices and Radiological Health. "Although the criteria others may be using to assess those studies show that some concerns are eliminated," Brown says, "unfortunately, they don't rule out a small, but significant, increased risk."
An immunology and epidemiology expert, Brown explains that an inherent problem in the studies is that some connective tissue diseases are extremely rare. "If you have a disease that has an incidence of 1 in 100,000 in the general population, for example, and you do a study of 750 women with implants, like the Mayo Clinic Study, then you wouldn't really expect to see even a single case of that disease," she says, "unless there's an exceedingly high--more than a hundredfold--increase in risk."
Small studies like these can rule out huge risks, but not smaller, yet significant risk increases that would only show up in studies that include several thousand women with implants, Brown says. Nor do the studies fully examine or answer whether the implants might in some women lead to symptoms not typical of classical disease manifestations.
Other Concerns
Brown also stresses that connective tissue diseases are not the only issue of concern, especially since they may affect a much smaller proportion of women with implants. The larger issue, she says, is the local complications that are clearly related to breast implants, such as rupture and migration of the silicone gel, capsular contracture, and infection.
"Of the two groups of women who consider getting implants--for breast reconstruction or for augmentation," Brown says, "the larger group wants them for cosmetic purposes. These are healthy women who may go out and get implants without a clear picture of what the possible risks are. They may end up going back in for surgery time and again and never be happy with the cosmetic effect."
In testimony before a congressional subcommittee in August 1995, FDA Commissioner David A. Kessler, M.D., stated that "Published studies to date suggest a rupture rate between 5 and 51 percent--an enormous range--and, unfortunately, we do not know with any confidence where within that range the real rupture rate lies." He also cited two studies that indicate the risk of rupture increases as the implants age.
Another concern--increased risk of breast cancer--has not been borne out by studies. "Several studies have indicated there is no increased risk of breast cancer in women with implants," Brown says. However, she adds, these women are not yet in the age group that is more prone to breast cancer, and it remains to be seen whether they will eventually have a higher incidence of breast cancer than women without implants. Long-term studies to look at this are under way.
Manufacturers' Studies
The events that led to removal of silicone implants from the market made it clear that prospective, or forward-looking, studies were also needed to answer important safety questions. Implant manufacturers agreed to conduct human trials in three phases: urgent need, adjunct, and core studies.
"The purpose of the first phase [urgent need] actually was simply to quickly provide implants to women who were already in the process of getting them for breast reconstruction or for another medical reason, and to bridge the time until the adjunct studies were begun," says Sahar M. Dawisha, M.D., a rheumatologist and medical officer who joined FDA's division of general and restorative devices in April 1993.
The women did, however, have to sign an informed consent form that summarized the risks and benefits of the implants. This form had not previously been required.
"The second phase, or adjunct, studies were intended to follow reconstruction patients for five years to assess short-term safety data, including rates of capsular contracture, rupture, and complications such as infection and hematoma [collection of blood that may cause swelling, pain and bruising]," Dawisha says. "These studies are open to all women wanting breast reconstruction with implants because of mastectomy, traumatic injury to the breast, or a disease or congenital disorder causing a severe breast abnormality. They do not include augmentation patients."
Mentor Corporation of Santa Barbara, Calif., began adjunct studies in 1992. According to Cathy Fox, clinical programs supervisor at Mentor, 14,803 patients are now enrolled.
The third phase, or core studies, Dawisha says, were intended to determine the full safety and effectiveness profile of the device, including rupture rates, quality-of-life benefits, extent of interference with mammography, and many more safety concerns--including rheumatologic assessments--that would need a large number of women. They were also to include augmentation patients. The sponsors, however, have not initiated these studies.
Saline Implants
Although many of the local complications of gel-filled implants are also associated with saline implants, the latter were permitted to remain on the market unrestricted for both reconstruction and augmentation. FDA considers saline-filled implants less risky, because although they have the same silicone rubber envelope as gel-filled implants, leakage or rupture would release only salt water, not silicone gel, into the body.
Nevertheless, FDA is requiring manufacturers to collect data on the saline implants as well, because the incidence of known risks (for example, deflation and capsular contracture) is not well defined. When the Medical Device Amendments were passed, it was determined that these devices would also eventually require premarket approval. In January 1993, FDA notified saline implant manufacturers that they would have to submit safety and effectiveness data for their products. In December 1994, the agency told them what type of safety and effectiveness data were needed, and delineated objectives and time frames for the trials. Saline implants will stay on the market while the studies are conducted, but the companies must report the laboratory, animal and clinical data in stages, and must provide written information on the known and possible risks of their products.
"Women considering saline implants should ask their doctor for a copy of the manufacturer's information sheet, a copy of the product insert sheet for the specific implant to be used, and a copy of the hospital informed consent form," says Barbara Stellar, FDA's breast implant information and outreach coordinator.
Stellar recommends women be given these documents at least a month before surgery is planned, if possible, so they can thoroughly discuss benefits and possible risks with surgeons, radiologists, and other women. These women should also ask their physicians about participating in the saline breast implant trials.
Brown hopes that further studies will more clearly define risks associated with all types of implants.
"We need to be able to tell women considering breast implants--whether for augmentation or reconstruction--the specific risks on which they can base their decision," she says. "It should be made clear that implants do not last forever, that they may break, and in what time period it is thought they might break. Most women have no idea implants break and there's very little information about rupture rates.
"The same is true for other complications, some of which may require further surgery or may cause the woman to be displeased with the cosmetic effect, which, of course, is the reason she got them," Brown says. "For a product that a person is putting in her body presumably for 20 years or more, we should have this information."
Marian Segal is a member of FDA's public affairs staff.
Signing a consent form is now part of the procedure for all women undergoing breast implant surgery. They must also be given information about the devices' known and possible risks.
Recent studies have shown, however, that there is not a large increased risk of traditional autoimmune, or connective tissue disease, from silicone gel implants.
Recently, however, a study to measure TDA in women with polyurethane implants found that a woman's risk of cancer from exposure to TDA released by the implant is negligible--about one in a million over a lifetime. FDA considers it unlikely that even one woman would develop cancer from these implants. The study supports the agency's original recommendation that women who are not having problems should not have the implants removed solely because of concern about cancer from TDA exposure.
--M.S.
Several laboratories are offering tests that claim to detect levels of antibodies to silicone that presumably indicate a leaking or ruptured implant.
FDA has not cleared or approved these tests for such purposes, and the agency has sent letters to several companies, warning of future regulatory action if they continue to promote the devices without a premarket approval application.
"There are important unresolved issues with these tests," says Peter Maxim, Ph.D., chief of the Center for Devices and Radiological Health's immunology branch of the division of clinical laboratory devices. "For one thing, the very existence of silicone antibodies has not been proven to the satisfaction of all scientists," he says. "Secondly, if antibodies are detected, is there in fact a correlation with the presence or the status of implants, or do they reflect prior environmental exposure? Silicone is in a myriad of products, including foods, medicines, and antiperspirants absorbed by the skin, to name a few."
The next problem, Maxim says, is that there are claims that extremely high antibody levels may indicate a leaking or ruptured implant. This, then, raises the question of what medical intervention, if any, should be taken.
Sahar M. Dawisha, M.D., a rheumatologist in FDA's division of general and restorative devices, adds that no one really knows what the clinical significance of an antibody to silicone means or at what level it is harmful.
"Furthermore," she says, "in autoimmune or connective tissue disease--where antibody tests are generally used--the presence of antibodies doesn't define the disease. A disease is defined by clinical signs and symptoms, and antibodies are used as supporting evidence."
Finally, John Nagle, consumer safety officer in the Center for Devices and Radiological Health's diagnostic devices branch, says, "The tests themselves may be harmless, but they sure are expensive, somewhere between $500 and $1,000," adding that "a lot of them are being done for litigation purposes rather than to help the patient medically."
--M.S.
To obtain a comprehensive packet of information on breast implant issues, request FDA's publication, "Breast Implants, An Information Update," by calling the agency's breast implant information line at 1-800-532-4440. For on-line information, see the Breast Implant Information on this Website.
Publication No. (FDA) 97-4262
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