On April 16, 1992, the FDA announced that breast implants filled with silicone gel would be available only through controlled clinical studies, despite the fact that they had been used for mammoplasty in millions of women around the world for more than 30 years. This decision led to a tremendous amount of debate among various groups because it was based not on sound scientific evidence, but rather, was heavily influenced by politics, the popular press, and vocal citizens groups, as well as the legal system. Silicone gel breast implants had been allowed to remain on the market after the 1976 enactment of the Medical Device Amendment to the Food, Drug and Cosmetic Act, with the understanding that the FDA would later require manufacturers to submit data demonstrating both safety and effectiveness.
The safety of silicone gel breast implants was first questioned in the 1980s when several independent authors reported a possible association between the implants and the subsequent development of connective tissue diseases.[2-7] Such reports led to general public concern fueled by popular media attention and multiple class-action lawsuits against the products manufacturers. It was in this environment that the FDA was forced to make its decision.
This article reviews the scientific evidence on the safety of silicone gel-filled breast implants that has come to light since the FDAs decision in 1992. The oncologic implications of silicone implants are highlighted. Issues regarding the imaging and treatment of an implanted breast are discussed, as is the potential carcinogenic effect of silicone.
Breast implants containing silicone gel were first offered to women desiring breast augmentation in 1963. These implants were later used for women seeking breast reconstruction following mastectomy. Over the past 3 decades, more than 1 million women have undergone breast implant surgery. These devices have facilitated the simplest, most economical form of breast reconstruction, with high patient satisfaction levels reported.
In 1976, the Medical Devices Amendment to the Food, Drug, and Cosmetic Act, enacted by the US Congress, gave the FDA the authority to regulate all medical devices, including breast implants. Since the implants were already in widespread use prior to the laws enactment, these devices were "grandfathered," meaning that, on the basis of past performance, they were accepted as safe and remained on the market, awaiting further study and review. At that time, the manufacturers were not required to provide further scientific evidence regarding the safety of the devices.
In June 1988, after public hearings by the FDAs Breast Implant Advisory Panel (as required by the 1976 law), the FDA classified silicone gel breast prostheses as class III devices. This designation requires each devices manufacturer to provide scientific proof of its safety and efficacy. The deadline for the submission of the manufacturers premarket approval (PMA) statement to the FDA was January 1991.
Seven manufacturers submitted PMAs. According to the FDA, three reports failed to include adequate safety and effectiveness data, while the remaining four were felt to provide insufficient data to ensure safety and effectiveness. The Breast Implant Advisory Panel held a hearing in November 1991, at which time, the FDA panel recommended that silicone gel-filled breast implants stay on the market, pending further study and evaluation by the FDA.
On January 6, 1992, Dr. David Kessler, commissioner of the FDA, requested a voluntary moratorium on the use of silicone implants. This action was based on new data relating to a possible link between the implants and autoimmune diseases, which had not been reviewed at the initial FDA advisory panel meeting. Manufacturers complied with the voluntary moratorium. On April 16, 1992, Dr. Kessler announced that the distribution and use of silicone-filled breast implants would be available only under clinically controlled trials. Patients who required implants for breast reconstruction would be assured access to these studies.
In contrast to the findings of the FDA, two reports issued in February 1993 and December 1994 by the Medical Devices Directorate of the United Kingdom Department of Health stated that "the increasing body of epidemiological evidence argues persuasively . . . that no link exists between silicone breast implants and connective tissue disease."[15,16]
Silicone (polydimethylsiloxane) is an inorganic polymer of silicone dioxide with elastometric properties. Silicone exists in liquid, gel, or solid form. Silicone was first used clinically in liquid form during World War II, when glass syringes were lubricated with silicone so that they would function reliably in combat. Hundreds of biomedical products in current use are made with silicone.
Four adverse health effects related to silicone gel breast implants have been evaluated: implant capsular contracture, rupture (failure), carcinogenesis, and autoimmune disease.[3,11,17] Each of these potential complications will be discussed separately below.
The most common reported complication of breast implant surgery is capsular contracture.[18,19] The formation of a capsule around a silicone implant is part of the expected inflammatory response to any foreign body.[4,15] Capsular contracture results in moderate to extreme hardening of the breast, tightness, mild to severe pain, and deformity or distortion of the breast. Although capsular contraction may be uncomfortable and cosmetically unappealing, it poses no danger to a womans health.
The diagnosis and measurement of the severity of contracture are inherently subjective, making it difficult to compare studies that have used different diagnostic criteria to evaluate this complication. The incidence and severity of contractures varied widely in two clinical series, ranging from 0.6% to 100%.[4,20] However, neither of these studies provided data on the duration of follow-up or diagnostic criteria.
In another series of 749 women (involving 1,454 breasts with implants), the overall incidence of capsular contracture was 17%. This complication was significantly less frequent after cosmetic implantation (12% after 5 years) than after implantation following mastectomy for cancer treatment or cancer prophylaxis (5-year rates, 34% and 30%, respectively). The risk of contracture increased over time in this series.
Capsular contracture after mammoplasty does not require the presence of silicone gel, however, because contractures have been shown to occur with saline-filled implants as well.[20,21] Movement of the implant in the tissue bed and a smooth rather than a textured implant surface have been implicated as causes of capsular contractures.
The word "rupture" has been applied to both the implant envelope and fibrous capsule that surrounds the implant. A mammogram can reveal a capsular rupture but not necessarily the failure of the implant envelope. A "silent rupture" refers to a failed implant within an intact fibrous capsule. In this case, the patient is asymptomatic and the mammogram is normal.
Implant age, trauma or injury to the breast, closed capsulotomy (a technique that uses manual pressure to break up fibrous scar tissue around the implant), and mammography have all been implicated as causes of capsular ruptures.[22,23] Rupture suggested by physical signs or confirmed by breast imaging requires the replacement of the implant.[22,23]
Several clinical studies have addressed the issue of implant rupture.[18,22-25] The incidence of silicone gel rupture is believed to be approximately 5%, based on several large clinical series.[11,18,24] The "gold standard" for confirmation of rupture is explantation and inspection of the implant. One reason why the durability of breast implants is not well known is that rupture is uncommon, and surgical exploration of asymptomatic women has been performed only rarely.
No clinical sequelae of implant rupture have been identified to date. Studies on tensile strength and fatigue resistance tested through cyclic loading, which might theoretically calculate implant durability, have not been performed to the FDAs satisfaction.
The potential carcinogenicity of any foreign implant has been a concern since the 1950s, when Oppenheimer et al demonstrated that implantation of any smooth-surfaced material in the peritoneum of rats could induce sarcomatous changes. The only cancers that have ever been attributed to silicone are connective tissue sarcomas in strains of rodents susceptible to cancera process known as "solid-state carcinogenesis" that is not unique to silicone. Silicone has not been shown to cause any other type of cancer in any animal species. Implanted silicone has not been associated with human sarcoma.
Several epidemiologic cohort studies have addressed the potential link between silicone breast implants and breast cancer.[26,28-30] None of the studies identified any increase in breast cancer among women with breast implants, as compared with women without implants.
Berkel et al performed a population-based, nonconcurrent cohort-linkage study of 11,676 patients in Alberta, Canada, with an average length of follow-up of 10.2 years. The actual incidence of breast cancer in the implant group was significantly lower than expected (P < .01). The authors concluded that this reduction in incidence was due to the fact that the women were drawn from a population already at low risk for breast cancer, and that the implants did not increase this risk.
A reanalysis of the Alberta cohort study used a more restrictive definition of breast implant recipients and a closer follow-up of 10,835 patients. This reanalysis concluded that there is no significant increase or decrease in breast cancer among women with implants.
Deapen et al retrospectively studied a cohort of 3,112 patients with breast implants in Los Angeles County. Petit et al conducted a similar study of 146 patients with breast cancer who received silicone breast implants for reconstruction. Finally, McLaughlin et al studied a cohort of 824 Danish women who received breast implants for cosmetic reasons only. None of these epidemiologic studies found a significant difference in the incidence of breast cancer between the implant and control groups.
The term "human adjuvant disease" was first used by Miyoshi et al in 1969 to describe a connective tissue-like illness in two patients whose breasts had been injected with paraffin(Drug information on paraffin) for augmentation. A possible relationship between silicone breast implants and connective tissue diseases was first proposed in 1982. Several other authors have published case reports of confirmed diagnoses of such disorders as systemic sclerosis, rheumatoid arthritis, and systemic lupus erythematosus in patients following placement of silicone-filled implants.[2,5,32,33] The term "human adjuvant disease" has been discredited as lacking precise and reproducible criteria and is no longer used.[17,34]
Silicone has been shown to evoke a fibrotic and granulomatous response in the tissue surrounding silicone implants in both animals and humans.[16,34-37] This response is characterized by fibrosis and cellular infiltration, primarily of fibroblasts and macrophages. Lymphocytes and leukocytes are observed less frequently. Whether silicone potentiates the progression of the fibrotic sequence to a scleroderma-like syndrome has not been established.
Antibodies to silicone-protein complexes have been identified in animal studies (mice, guinea pigs), but the findings were not specific to breast implants and the antibodies could not be correlated with rheumatic disease. Studies in which silicone was injected into experimental animals, even with the most potent adjuvants, failed to elicit any evidence that silicone serves as an antigen. Animal studies have not shown an association between silicone administration and the development of a scleroderma-syndrome in a mouse model. There is no evidence that any silicone product, acting alone, can facilitate the induction of autoimmune disease in animals.
Clinical Studies: In humans, enzyme-linked immunosorbent assay (ELISA) techniques have been used to measure antibodies against silicone in patients with breast implants. Statistically significant differences between the serum from controls and patients with implants were observed for mean values of total immunoglobulin G (IgG) binding.[34,38] However, it is unclear whether the assays used were specific for antibodies to silicone; moreover, no information was provided about the patients with implants, such as prior surgery or the presence of other prosthetic devices.[16,34]
In one series of 300 patients with silicone breast implants and musculoskeletal complaints, 50% had elevated levels of serum antinuclear antibody titers. Another study of 156 women also found a small subset of patients with elevated autoimmune antibodies. The association between these abnormal laboratory values and the development of autoimmune disorders in these patients is currently unknown.
Several epidemiologic studies that used cohort, case-control, and cross-sectional designs have failed to show an increased risk of developing well-defined rheumatic diseases following the placement of silicone breast implants.[18,40-45] In a survey of 378 patients who underwent cosmetic breast augmentation between 1970 and 1981, Weisman et al could not discern any relationship between implants and rheumatic disease. Similarly, Giltay et al surveyed 287 women who had silicone breast prostheses implanted between 1978 and 1990 and found no increased prevalence of rheumatic diseases.
Gabriel et al performed a cohort/medical record database review study of 749 patients and 1,498 community controls. Over a mean follow-up period of 8 years, they failed to uncover any association between breast implants and connective tissue diseases.
Sánchez-Guerrero et al conducted a large cohort study involving 1,183 patients with implants and 86,318 participants without implants. No increase in the risk of defined connective-tissue disorders was found in the silicone implant recipients.
Finally, Hennekens et al retrospectively studied 395,543 female health professionals, 10,830 of whom reported having breast implants. This study suggested a small, nonstatistically significant increased risk of connective-tissue diseases among women with breast implants.
Differences in methods among these epidemiologic studies preclude a formal meta-analysis evaluation. However, taken together, these studies suggest no substantial increase in the overall risk of well-defined autoimmune diseases resulting from silicone breast implantation.
The potential association between breast implants and specific rheumatologic disorders has also been studied extensively by the case-control method. Hochberg et al performed a case-control study of 869 patients with scleroderma and 2,061 age- and race-matched controls. Dugowson et al conducted a case-control study of 349 patients with rheumatoid arthritis and 1,456 age-matched controls. Neither of these studies showed an association between silicone implants and the development of scleroderma or rheumatoid arthritis.
The coexistence of implants and an autoimmune disorder may be coincidental, since autoimmune diseases tend to occur in young, thin women, and these are the same individuals who request breast augmentation.
Current Recommendations: The FDA currently advises that women who are not experiencing problems with their breast implants need not have the implants removed. The normal risk associated with all surgical procedures is likely to be greater than any real or speculative risk of retaining breast implants.
Given the lack of data implicating silicone breast implants as a cause of autoimmune disorders, the American College of Rheumatology has issued the following statement: "There is no convincing evidence that these implants cause any generalized disease."