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
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
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 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."
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