In May 2000, the Medical Devices Agency (MDA) convened an Advisory Group (consisting of toxicologists, plastic surgeons and a lay representative) to consider new data on the safety of Trilucent breast implants. The Group considered the available scientific evidence, made an assessment of the risk to patients and, based on this assessment, provided advice to MDA.

Background

Trilucent breast implants consist of a silicone elastomer shell with a lipid filler based on soyabean oil. Over 9000 implants have been implanted into almost 5,000 women in the UK.

In March 1999 the Medical Devices Agency (MDA) raised concerns about the lack of long-term safety data on Trilucent breast implants particularly in relation to the breakdown of the lipid filler. An independent view on the relevant data was sought from four members of the Department of Health's Committee of on Toxicity (COT) in March 1999. The COT members raised two specific concerns at that time: the apparent irritation following rupture and the apparent increase in levels of degradation products over that upon which the manufacturer had undertaken their initial safety assessment. They advised that further data should be obtained to allow a risk assessment to be made. As a result of these concerns the company voluntarily withdrew Trilucent breast implants (in March 1999) as a precautionary measure. MDA also issued advice to the Health Service in the form of MDA Advice Notice (AN1999(01) http://www.medical-devices.gov.uk/an1999.htm)

The Advice Notice stated that in 1999 there was no safety information to suggest that removal of Trilucent breast implants was indicated but that women should be advised to seek an immediate clinical consultation if they noticed unusual breast swelling or inflammation associated with their Trilucent breast implants.

New information

After the March 1999 withdrawal from further sale of Trilucent breast implants, MDA required the manufacturer to carry out further toxicological testing on the filler used in Trilucent breast implants. The company has now carried out chemical analyses which have established the general nature and amount of breakdown products generated when the filler degrades.

The company had provided MDA with preliminary data on the levels of various degradation products measured in samples obtained from both explanted Trilucent breast implants and retained stock. The explant samples had not been collected under controlled conditions. The samples from retained implants were taken from devices which had been stored under the manufacturer's recommended storage conditions.

The samples from the majority of the explants and retained implants contained millimolar amounts of at least one type of aldehyde degradation product. Other samples did not contain amounts greater than the limit of detection of the measuring technique (10 micromolar). Samples contained millimolar (or greater) concentrations of intermediate degradation products (hydroperoxydienes). The company was unable to find a correlation between the concentrations of degradation products in explants and any known use factors.

The Advisory Group discussed this new information on 19 May 2000.

The Group considered that once the production of these degradation products has been initiated, peroxidation will continue. The concentrations of these degradation products will increase after sample collection in the absence of adequate analytical controls. The lack of control on sample handling (especially the time between explantation and analysis) complicated the assessment of the company's results.

Although a fraction of the degradation products measured were accepted as being post-sampling artefacts, the Advisory Group concluded that, at the concentrations measured, such artefacts would not be sufficient to disregard the findings of the tests.

Aldehyde degradation products

The metabolism of fats in the body produces low concentrations of degradation products. The degradation products are known to have a number of biological effects. These include effects on cell proliferation .Certain degradation products are known to be cytotoxic at micromolar concentrations; they are also known to be very reactive towards primary amino groups in proteins and DNA.

Genotoxic risk

The Advisory Group agreed that:

• at the reported levels, aldehydes would react (form adducts) with protein and DNA;
• this would result in a genotoxic hazard;
• leakage (or "bleed") through the implant shell could result in continuous exposure to this hazard and rupture would lead to a large single exposure;
• deficiencies in the data provided did not permit accurate estimation of the genotoxic risk, but this risk could be significant;
• the manufacturer's previously conducted mutagenicity studies were technically flawed both in the use of extracts and in the absence of aged characterised oil therefore they did not provide any reassurance concerning the genotoxic potential of the degradation products.

The Advisory Group noted that clear evidence of a possible increased cancer risk in women was unlikely to be available for many years.

Reproductive toxicity risk

The Advisory Group concluded that exposure to genotoxic degradation products resulting from diffusion of filler through the shell (bleed) or from rupture posed a potential reproductive toxicity risk whilst the implants were present. However due to the short half-lives of the degradation products, the Advisory Group's opinion was that this risk was unlikely to remain after explantation.

The Advisory Group agreed that it was prudent to advise that pregnancy should be avoided (by use of contraception) until the implants were removed, but that this precaution would not be necessary after explantation.

In the Advisory Group's opinion, the possibility of genotoxic degradation products migrating from implants to breast tissue and milk could not be discounted. It was therefore prudent to recommend that breast-feeding should be avoided prior to explantation of Trilucent breast implants.

The Group stressed that the advice on pregnancy and breast-feeding were precautionary. The advice was based on their inability to exclude these risks on the data available rather than any direct evidence for such effects.

Capsule

The Advisory Group was informed that the capsule formation around Trilucent breast implants differed from that observed with other breast implants. The capsule felt like lumps around the implant and the shell appeared incorporated into the capsule. Although these differences might be due to other causes (such as the surface texture of the implant), it was the Advisory Group's opinion that the possible involvement of degradation products in producing this unusual capsule morphology could not be ignored.

Clinical issues

It was the Advisory Group's opinion that women should be provided with as much information as possible, including the uncertainties and areas where no information was available. Women had the right to make an informed choice on whether or not to undergo explantation in response to the known facts.

The Advisory Group recognised that the majority of women would not be content with explantation alone but would want replacement breast implants.

The Advisory Group emphasised that there were other aspects that needed to be included in a comprehensive package of care provided to women with Trilucent breast implants. These included: clinical monitoring of the consequences in women (whether or not they chose to undergo explantation); possible psychological effects both from the possible loss of the breast and also worry about long-term consequences.

Recommendations

The Advisory Group concluded that:

• there was an explicit risk from the potential release of genotoxic products as a result of the on-going "bleed" and the possible rupture;
• although there were insufficient data to establish an increased risk of cancer or reproductive toxicity, these possible risks could not be excluded
• all women with these implants should be informed that removal of Trilucent breast implants was recommended because of these risks.

The Advisory Group stressed that even if Trilucent breast implants were explanted from women, additional studies would be needed to further characterise the risks and to provide further information to these women.

The Advisory Group concluded that there was no data on the safety of implanting other breast implants subsequent to the removal of Trilucent breast implants and women needed to be informed that there was no information either way on this matter.

Last updated : 6 June 2000

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