The history and safety of breast implants

INTRODUCTION

Through all ages the human beings are desire and strive to improve their body image or to undo the deformities due to congenital, traumatic or other reasons. Naturally the female breasts as a symbol of sexual attractiveness and fertility are maybe the most prominent target of this desire. Nowadays the woman can choose from a spectrum of methods from autologous fat tissue transfer to silicone breast prostheses. Especially in the field of aesthetic breast enlargement there is a wide spectrum of silicone breast implants. They range in shape and size, in profile from low to extra high, in surface from smooth and micro-textured to highly textured and in fillers from saline to various cohesivity silicone gel and they are even equipped with an identification chip. Also the preoperative measurements, markings, sizers etc. were developed almost to perfection. The breast enlargement and reconstruction has however a long and not a straightforward history and still there is no truly optimal method with no risks or adverse effects.

Each implant used in human medicine can fail regardless of its manufacturer or used material. The probability of failure increases with time since implantation. Specifically, breast implants are medical devices used for augmentation of the breast size, for reconstruction of the breast after mastectomy or for correction of congenital breast asymmetry. The breast implants in general are probably the most frequently used medical implants. It is estimated that there are about 5−10 million women with breast implants in the world. It is not possible to find out the exact number due to a fatal lack of regulations and systematic obligation to register the use of breast implants in all countries in the world (1). According to the American Society of Plastic Surgeons National Clearinghouse of Plastic Surgery Procedural Statistics, in 2010 there were 296,203 aesthetic breast augmentations and 93,083 breast reconstruction procedures performed in the United States. The use of gel filled implants and saline filled implants are approximately equal.

THE HISTORY OF BREAST AUGMENTATION

The history of breast enlargement dates back as far as the 1890’s. Probably the first clinical attempt to enlarge the breast was done by Czerny in 1885, using autologous fat tissue. He transplanted a lipoma from the lumbar region to restore the breast parenchyma defect after removal of an adenoma in an actress. He reported that the breast remained physiologically and nicely shaped and lipoma was well taken and did not grow (2). The use of autologous fat continued and Bartlett in 1917 reported usage of subcutaneous fat from the abdomen, thighs and buttocks to reconstruct the breast. He noticed the need to use approximately 50% more fat tissue because of absorption. The reconstructed breast restored the volume of the other breast within 6 months but was less ptotic and firmer (3). The absorption of fat was quite extensive with only about one fourth to one half of the fat graft survival, therefore new techniques evolved. Berson modified the technique of May´s fat-fascial graft into dermal-fat-fascial graft with reported survival from 60 to 90% (4,5). Although the results were encouraging, soon there were reported cases of irregular liquefaction and absorption causing asymmetry and also donor site deformities (5). Murray in his patients found that transplanted graft underwent necrosis with calcifications and fibrosis in almost all cases resulting in unnatural breast shape and graft feeling like “discrete stony hard lump”(6). The technique was gradually abandoned and replaced by current fat micro-grafting technique by Coleman.

Almost simultaneously with the usage of autologous fat graft the technique of breast enlargement with synthetic materials evolved. In 1899 the Austrian physician Dr. Robert Gersuny attempted the breast augmentation with paraffin injections (7,8). However, this led to tissue retraction, granulomas, ulceration and hardening of the breast (9,10). It was also reported, that paraffin injected into the breasts can cause systemic complications such pulmonary, cerebral or retinal embolism, paraffinoma or chronic polyarthritis (11−13) and the technique fell out of favour within few years.

After the Second World War new breast filler emerged – the liquid silicone. In the early 1950’s, Japanese invented the technique of silicon injection for breast enlargement. The mixture of silicon and silicon diluent was mixed and a catalyst was added afterwards. The liquid silicon was injected into the breast and the patient was kept in recumbent position with breasts fixed in desired position and shape for about 24 hours. In this time the liquid silicon turned to gel. Material was said to be well tolerated with no inflammation or other complications (14,15). Within a decade, however, the results had to be revised as the same complications as in paraffin injections occurred and they were even more prominent due to unspecialized persons performing the procedure. Silicon particles spread in the form of satellites throughout the entire breast tissue. Inflammation and silicone fistulas occurred with breast parenchyma destruction (16). Liquid silicone for breast augmentation is now uniformly condemned.

The use of composite block material as an exogenous prosthesis for breast enlargement was probably first reported by Schwarzmann in 1930. Glass balls were implanted into the breasts. These glass balls were in use until 1942 (17).

In 1952 the Ivalon – a polyvinyl sponge - was reported to be an inert non-toxic and non-carcinogenic suitable material for breast augmentation. The research was done in dogs (18) and in 1953 the highlighted article about this prosthesis was published in Pageant Magazine by a famous Hollywood surgeon Dr. Robert Franklyn. He named his polyvinyl sponge breast prosthesis for use in human medicine as Surgifoam (19). The initial results were satisfactory however over time developed complications such as infection, contraction of the sponge with decreased volume and unfavourable tissue reaction with discharge. Therefore a compound prosthesis was invented with plastic film outer shell filled with Ivalon sponge and better results and natural breast shape and feeling were reported (20).

Polystan sponge was made of polyethylene tape. No extrusion or malignant changes were confirmed in rodents (21). The clinical application was reported by Gonzales-Ulloa in 1960 with no complications in 10 patients after 4 year follow up (22).

Polyurethane (polyester) is derived from polypropylene ether. This plastic was used in 15 patients in 1962. Shrinkage of about 40% of the original volume was observed and an inflammatory reaction occurred in 10% of patients (23).

In 1953 there was the first suggestion of a possibility to use silicone rubber as a permanent prosthesis because of its medical properties – inertness, non-toxicity and non-carcinogenicity (24). The first silicone gel breast prostheses were introduced in 1960’s by Dr. Cronin, a plastic surgeon from Houston and his resident Gerow with Dow Corning Corporation (25). The first Silastic implant – a silicone rubber shell filled with silicone gel was implanted in 1962 by Gerow (19). In the same time, dimethylpolysiloxane prostheses with the similar properties were developed in Japan by Akiyama. His material could have various elasticity and hardness and could be manufactured as a solid piece, sponge or gel (26). Several refinements such as reduction of shell thickness, fixation patches, less viscous gel etc. were put into practice to perfect the implants. Results from this new type of prostheses were very satisfactory but complications developed in patients with reported frequency from 40 to 70%. The most frequent complication was capsular contracture followed by infection, haematoma and implant protrusion. In 1965 in France the saline filled silicone implants – Simaplast – were presented by Dr. Arion. The deflation rate however was up to 50%. In 1980’s the polyurethane foam coated implants Meme by Surgitec reduced the rate of capsular contracture, but due to toxic carcinogens produced by foam degradation their popularity decreased in 1991 (27); they are still in use, however.

In late 1980s some signs of potential danger from silicone particles such as autoimmune diseases, carcinogenesis and others attracted the The United States Food and Drug Administration (FDA) attention. It finally resulted in FDA moratorium on silicone implants in 1992 (27). It took a long time to recover the silicone gel filled implants reputation and from 2006 a new era with an excessive evolution of silicone implants began.

However, since the ban on silicone gel implants, research has been conducted to find suitable replacement. The first choice were of course the silicone shell implants filled with normal saline. The saline is completely harmless and if the shell ruptures, solution is rapidly reabsorbed. The use of these implants increased from 10 to 95% within one year in the USA market. The implants filled with oils (peanut, triglycerides, soybean) were also presented as alternatives. In the United States these prostheses did not progress beyond experimental stage. Biocompatibility of these fillers is questionable as hydrophobic oils are difficult to disperse, bacteria can grow in vegetable oils and degradation of oils is possible within the shell. Study confirmed that high percentage (34%) of these implants bleed and the capsular contracture Baker 3−4 was present in as high as 45% (28,29). Another substitute –the hydrogel implant has better lubricating properties and does not harbour bacteria. However, a case series concluded, that these implants are not truly safe as 59% of implants had to be removed within 4 years. The main reasons were increase in volume and capsular contracture (30).

THE SAFETY OF SILICONE BREAST IMPLANTS

From the beginning of silicone breast implants use there were some doubts and questions about their safety. In 1977 the first lawsuit was won by Houston attorney for his Cleveland client – a woman who claimed, that her ruptured breast implant and subsequent surgeries had caused her pain and suffering. In the early 1980´s the Public Citizen Research Group warned, that silicone implants can cause breast cancer. The concern about silicone implants safety exploded in 1990 after the talk show “Face to face with Conie Chung”. This talk show described in details the horrific troubles of breast implants. An enormous public pressure followed on government official to act that resulted with FDA decision to stop the use of silicone gel filled implants on 6^th January 1992 in the USA despite the lack of evidence that the device can cause disease or that it is dangerous in any other way. The only argument was that manufacturers had not adequately demonstrated their safety (31).

In the meantime while sufficient scientific data were gathered to prove silicone gel filled implants safety a wide space was opened for a variety of litigation and lawsuits against implant manufacturers. Almost every disease or symptom complex has been blamed on the breast implants (32). In 1994 the Dow Corning Company was facing bankruptcy with almost 20 thousands lawsuits and about 410 thousands potential claims.

The inertness and safety of silicone breast implants however soon became sufficiently proved by high quality scientific studies. In 1994, the Mayo Clinic published an epidemiologic study, which found no increased risk of connective tissue disease such as Sjögren´s syndrome, lupus erythematodes, scleroderma, rheumatoid arthritis etc. in women with silicone implants. It was supported by The American College of Rheumatology in 1995 and some other researches (33−35). In 1997, the American Academy of Neurology reported that existing research showed no link between silicone implants and neurologic disorders (36). The Journal of National Cancer Institute published a review of studies concluding that there is no evidence for silicone implants to cause any cancer (37). The most questionable was cancer of the breast, uterus, brain and lung and non-Hodgkin´s lymphoma. On the contrary, some studies suggested even lower rates of breast cancer in implanted women (38). This is most probably due to the fact that women with breast implants are often under regular medical monitoring and also the breast cancer is diagnosed in early stage more frequently in those women. In 2008 there were the first signals about anaplastic large cell lymphoma (ALCL) and its association with silicone breast implants (39). ALCL is a very rare lymphoma and it seemed to be more frequent in women with silicone breast implants. According to a comprehensive FDA survey there were about 40 ALCLs diagnosed in women with the implants. The FDA conclusion is that in accordance with the recent knowledge there is a very low but significant risk of ALCL in women with breast implants; nevertheless the use of implants is safe (1,40). There was also a suspicion that breast-feeding from augmented breast can influence the child’s health. Muscle weakness and fatigue, oesophagus dysmotility causing swallowing problems and undefined skin manifestations were reported. This was also rejected by a study performed in Sweden and Denmark (41,42).

THE MATERIAL AND MANUFACTURE OF SILICONE BREAST IMPLANTS

The recent breast implants are manufactured from silicone. Silicone is used for medical purposes from early 1940^’s because of its biocompatibility and durability. It is used for joint prostheses, drains, catheters, shunts, stents, syringes, needles, heart valves, instruments and of course implants for aesthetic surgery. The safety of silicone for medical use was acknowledged by Medical Institute (Washington USA) in 1999 (43). Silicone is also extensively used in food and cosmetic industry.

The breast prostheses are produced from medical silicone – polymer polydimethylsiloxane. Silicone has six forms – fluid, emulsion, compound, lubricant, resin and elastomer. The elastomer is ideal for implant’s shell. The silicone gel is made from silicone fluid - the polydimethylsiloxane chains lightly cross-linked through vinylhydrogen bonds or T-shaped silicon structure. The density (cohesivity) correlates with the number of links between silicone polymers (44).

The implant consists of a silicone shell and a filler. The shell must be very stable and strong. It is tested to a minimum of 450% elongation at breaking, minimum 11.12 Newton force at breaking, minimum 3.5 Newton tear force at breaking and a maximum of 10% tensile set. There is not a special request for gel bleeding, however some manufacturers stated that the accepted total value after 10 years should not exceed 2.5% of the original implanted volume. Patch joint integrity test require that no failure of joint (delamination) occurs when the shell is extended to 300% elongation and held at this value for a period of 10 seconds. Fatigue resistance test, according to the standard, requires that no cuts, tears or cracks are visible at 10x magnification. Destructive testing is based on the vertical drop of a specified mass on the implant and no rupture should occur. Although there is no standard requirement, some manufacturers provide also static resistance rupture test using compression device machine. The maximum force applied by equipment is 10 thousands Newton and implant should resist up to the maximum force (45,46).

The standards for silicone gel used for breast implant’s filler are very strict. The filling gel meets the requirements of the test if there is no separation and the projecting length of the gel is less than 30 mm. The size of particles is strictly defined and only a minimum of under-sized particles that can penetrate the shell is tolerated. High quality gels contain 1−2% molecules of low molecular weight (3−20 silocane units, molecular weight 20-1500). The standard gel for breast implants is Nusil MED3 6300 (Nusil Technology LLC, Carpinteria, CA, USA) with small particles content less 1% (45−47).

Biological testing of the implants require less or equal to 600 colony-forming units per device after sterilisation testing aerobic, anaerobic bacteria, spores and fungi and limulus amebocyte lysate. The endotoxin units should be less or equal to 0.5 per ml (45,46).

During the evolution of silicone breast implants a systemic refinement projected into manufacture process in accordance with the results from patient’s follow up and experience gained. The first generation of implants were those proposed by Dr. Cronin and they were manufactured by Dow Corning Corporation since 1962. The implants had smooth, quite a thick shell, viscous gel and Dacron patch and they were typical for high bleeding, they were firm to touch and there was frequent capsular contracture. The second generation of implants came to the market in 1972. They had thinner smooth shell and less viscous gel therefore they were more natural to feel, but a high rate of capsular contracture and rupture was the price paid for it. The third generation of implants was introduced in early 1980’s. The prostheses had an additional fluorosiloxane barrier layer to prevent gel bleeding and rupture and more cohesive gel. The effect was as expected improved longevity and reduction of gel bleeding and ruptures, however the incidence of capsular contracture was not reduced. Inspired by polyuretane foam coated implants with lower rate of capsular contracture, a forth generation of implants emerged in middle 1980’s with textured shell. The capsular contracture was significantly reduced. The early 1990’s welcomed fifth generation of breast silicone prosthesis. Characteristic sign of the latest generation is increasing gel cohesivity in the terms of “form stable implants”. The shape is maintained longer, the longevity of implant is enhanced and the gel does not disperse even in case of a complete shell rupture (44).

THE REGULATORY PROCESS IN BREAST IMPLANTS

In the USA the regulatory process for medical devices started in 1976. In the same year the FDA considered breast implants to be a moderate risk − Class II − medical device. This type of medical devices needs to comply with general control and performance standards. Breast implants were reviewed through premarket notification process. However in late 1980´s the concerns about safety of silicone gel filled breast implants emerged and in 1988 FDA reclassified breast implants into Class III high risk medical devices that need premarket safety approval and call for manufacturers to prove the implants were safe and effective. In 1992 the FDA concluded that there is still no adequate scientific safety evidence to address concerns about certain complications and silicone gel filled breast implants were removed from the US market. To satisfy public health needs, the gel filled implants were available for reconstructive purposes and also saline filled implants stayed on the market for women seeking breast enlargement.

As a condition for approval FDA demanded each manufacturer to provide six post approval studies to define implants characteristics and behaviour. The studies are:

1. Core Post-Approval Studies to assess long-term clinical performance of breast implants
2. Large Post-Approval Studies to assess long-term outcomes and identify rare adverse events by embracing at least 40,000 silicone gel-filled breast implant patients and following them for 10-years.
3. Device Failure Studies to further characterize the causes of failure of explanted devices over a 10-year period.
4. Focus Group Studies to improve the format and content of the patient labelling.
5. Annual Physician Informed Decision Survey to monitor the process of how patient labelling is distributed to women considering silicone gel-filled breast implants.
6. Adjunct Studies to provide performance and safety information about silicone gel-filled breast implants provided to women in the period prior to approval, when implants could only be used for reconstruction (1,48).

In 1999, the Institute of Medicine (IOM) released a comprehensive report of the published literature and ongoing studies on breast implants, entitled “Safety of Silicone Breast Implants”. This report clearly distinguished the differences between local complications and systemic health concerns of the breast implants. The local complications, which included pain, rupture, capsular contracture, disfigurement, and infection, lead to medical interventions. But most importantly, the report concluded that there was no evidence that silicone breast implants caused systemic health negative effects such as cancer or autoimmune disease (43).

In 2000 the FDA gave its approval to INAMED´s (later bought by Allergan) and Mentor’s saline-filled implants and in 2006 to silicone gel-filled breast implants. The FDA based its approvals on IOM study and the manufacturers’ clinical studies. Despite quite frequent local complications the FDA concluded that the benefits and risks of breast implants were sufficiently understood for women to make informed decisions about their use (1,48).

The European Union (EU) started to harmonize their rules regulating medical devices in 1990. The regulations for non-active medical implants (including breast implants) were coordinated in 1993. The enforcement of stated directives is the responsibility of each of the EU countries. In accordance with the current system, a medical device can be sold in each EU country once the product holds CE (Conformité Européenne) mark obtained in any EU member state.

In the European Union the regulatory framework for all medical devices is built on three main directives:

1. Council Directive 90/385/EEC on the approximation of laws of the Member States relating to active implantable medical devices
2. Council Directive 93/42/EEC concerning medical devices and
3. Directive 98/79/EC of the European Parliament and of the Council on in vitro diagnostic medical devices

Manufacturers shall ensure that the devices they place on the EU market are in accordance with the legal requirements and do not compromise the health or safety of patients and users.

Breast implants are in the highest risk class (i.e. Class III) since 2003 and as such are subject to the most stringent pre-market review. Silicone breast implants shall meet two standards - EN ISO 14630:2008 − Non active surgical implants – general requirements and a special standard EN ISO 14607:2009 – Non active surgical implants – mammary implants – particular requirement. The notified body is required to examine either the design dossier regarding the device or a type of a device, it must audit the Quality System, it must periodically carry out appropriate inspections to make sure that the manufacturer applies the approved quality system and at last it is obliged to perform unannounced visits to the manufacturer to check the accuracy of the manufacture process (45,48).

CONCLUSION

The breast implants generally seem to be rather stable within the first 6-8 years, thereafter the risk of rupture increases. For currently used fifth generation of implants the rupture risk of 10−15% within 10 years after implantation seems to be a reasonable estimation. Other main risk factors for implant rupture, apart from time after implantation, were identified. They include physical and chemical properties of the implants, the implantation procedure itself and patient specific factors such as accidents, occupational and sport habits.

The frequency of local complications among breast implant recipients generally is reported to be 17−36%. The capsular contracture is the most common cause for revision surgery followed by haematoma, infection and pain. The breast implant’s long-term consequences such as systemic diseases, breast cancer, lymphoma, immunological effects, suicide and psychological issues were all excluded by scientific high quality epidemiological studies. The only issue that stays in question is Anaplastic Large Cell Lymphoma that was reported in about 40 women with breast implants. However, from current studies, the frequency of ALCL among women with breast implants seems to be minimal but significantly higher that among woman without implants.

We can now conclude that so far there was no other medical device that was a subject of such detailed and strict investigation and testing than silicone breast implants. It is currently well demonstrated that implants are safe and can be used for breast reconstruction and aesthetic augmentation procedures. Prosthesis can rupture and cause local symptoms but there is no evidence that it can be a systemic health hazard for patients.

Address for correspondence:

Martin Molitor, M.D., PhD

Department of Plastic Surgery

Na Bulovce Hospital

Budínova 2

Prague 8, 180 81

Czech Republic

E-mail: martin.molitor@bulovka.cz