Safety issues

Rupture and gel bleed
Rupture

• Rupture is the development of a split or hole in the shell of a breast implant. Ruptures can arise because of weakness in the implant shell material or as a result of damage to the implant. Rupture should not be confused with gel bleed, in which low molecular weight components migrate through the intact implant shell.
• There is no doubt that some breast implants will rupture. It is not possible to obtain an accurate estimate of either the rate of rupture nor its incidence at any particular point in time for breast implants in general, different manufacturers or any particular model.
• The literature on rupture is confounded by differences in the definition of rupture, differences in the accuracy of detection methods and limited identification of the implants.
• Rupture can only be definitively detected following surgical removal of breast implants, so estimates of rupture rate in the implanted population as a whole must rely on the less accurate non-invasive imaging methods.
• The published information regarding rupture rates relies mainly on the performance of the earlier generations of breast implant designs. There are differences in shell structure resulting from the barrier layer, which could affect its mechanical properties in addition to decreasing gel bleed. Caution must be exercised in any extrapolation of their performance to current designs.
• Patients and surgeons require more information on the performance of current implant designs in vivo to enable them to make informed decisions.

Fate of gel bleed
1. Introduction
Silicone polymers contain a range of different sizes of silicone molecules ranging from small amounts of the compounds used to make the polymer (low molecular weight silicones) to a variety of sizes of polymer chain (with molecular weights from 7000 upwards, average 30000). The precise composition of a silicone varies with its intended physical properties. The typical levels for the individual low molecular weight silicones in breast implant gel are 800-1500 ppm (i.e. 80-150 mg/100 g). These low molecular weight silicones have a number of other uses including hair care products, skin care products, antiperspirants and deodorants.

The absorption and distribution of these low molecular weight silicones, like all small molecules, is determined by their solubilities in water and fat. The water solubility is important for transport to and from cell membranes and the fat solubility determines the transport into cell membranes. As its weight increases the size and shape of the molecule become far more important influences in the ability to absorb and distribute compounds. For the largest molecules absorption and distribution rely on the specialised mechanisms evolved to handle small amounts of naturally occurring macromolecules.

2. Absorption and distribution
Transport of a molecule requires it to go into solution to reach the cell membrane, pass through the lipid cell membrane and go into solution to leave the cell membrane. All of these processes are controlled by the physicochemical properties of the molecule and governed by fundamental laws such as Fick's law. The cohesion of a membrane barrier is determined by the tightness of intercellular junctions. T

hree factors influence the distribution (movement) of molecules in the body solubility, lipophilicity and molecular size/shape. For small molecules (up to 500-600 Da) the last can be ignored, whereas for medium molecules (600-1500 Da) the interplay of all three properties is critical. The molecular size/shape is the most important factor for large synthetic molecules. These molecules are mainly transported by specialised mechanisms e.g. following engulfment by cells.

3. Metabolism and excretion
In order to excrete small molecules it is desirable to increase their hydrophilicity and/or size. This is the main function of foreign compound metabolism. Phase 1 reactions increase the hydrophilicity e.g. by hydroxylation whilst phase 2 conjugation reactions increase molecular weight. These reactions are performed by enzymes within the cell. The distribution of silicone and its precursors is governed by the same processes. The silicone polymer (PDMS) is a large crosslinked molecule hydrophobic molecule that is essentially insoluble. The distribution of silicone polymer is essentially restricted to phagocytosis.

The short chain linear and cyclic precursors have been demonstrated to absorb, distribute, metabolise and excrete in relation to their solubility, molecular weight and lipophilicity. As their molecular weight increases their solubility and oral absorption decrease, essentially reaching zero at more than 8 siloxy units. For those short chain molecules where half lives were measured these were in the order of hours to days. The metabolism of the short chain precursors has been studied demethylation reactions have been shown to occur. However in no case has the loss of more than two methyl substituents been shown, there is no metabolism to silicates. There is no evidence of demethylation of silicone polymer, this probably reflects its inability to cross cell membranes and fit into enzyme active sites.

Cancer
The risk of tumours arising in the vicinity of silicone gel implants was considered by the Department of Health's Committee on Carcinogenicity (COC) during 1989 and 1990, following concern over studies in rats which showed an association between silicone gel breast implants and local sarcomas. These tumours develop as a result of mechanisms which are not relevant to humans and the COC concluded, on the basis of all the available information, that the possibility that silicone gel implants would induce local tumours in humans was remote.

In its 1998 report, the IRG said that “analyses of large groups of women both with and without breast implants have shown that there is a slightly reduced incidence of breast cancer in women with breast implants. Studies looking at the incidence of other cancers have failed to demonstrate a statistically significant increase among women with breast implants.” 1 The Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC) provides expert advice to the Chief Medical Officer and UK Government Departments.

Mammography
General
There is no evidence that women with breast implants are at increased risk of breast cancer. It is important that all women including those with breast implants participate in a routine programme of breast cancer detection, including both breast self examination and (for women over 50) mammography. Mammography is a special X-ray examination of breast tissue used in the early detection of breast cancer. The NHS Breast Screening Programme provides free screening every three years for women, in the UK, aged 50 and above. More information on breast screening in the UK can be found on the NHS Breast Screening Programme website (external link).

Breast implants
The presence of silicone gel filled breast implants may interfere with standard mammography as silicone is radiopaque, and the physical presence of the implant may obscure part of the breast tissue and distort breast structure. The amount of interference varies depending on a variety of factors including the position of the implant. However, studies indicate that breast cancer in women with breast implants is not diagnosed at a later stage compared with women without implants. Deposits of calcium-containing salts (calcification) are known to occur in the tissue around implants. These deposits are believed to increase with time and may remain once the implant has been removed. Although these calcifications are not considered harmful in themselves, they can be seen on mammograms and may interfere with mammographic findings and interpretation of results. Since calcification may also be seen in women with breast cancer, further tests (including a biopsy) may be needed to differentiate between calcification due to breast implant or related to cancer.

To increase sensitivity, a different mammographic technique needs to be used in women with breast implants. It is therefore vital that the centre carrying out the mammography is aware of the presence of breast implants (and the type of implant if known) before the mammography takes place. Mobile breast screening units may not have the necessary facilities for screening women with breast implants and it may therefore be necessary to refer these women to a fixed breast screening unit. Concern regarding the possibility that the pressures used during mammography might damage the implant should not discourage women from undergoing this procedure. There is only anecdotal information in the literature regarding the breast implant rupture during mammography. The radiographer should, however, take this risk into account when performing the mammography.

Both the Royal College of Radiologists and the NHS Breast Screening Programme have issued guidance to radiographers on mammography in women with breast implants. The UK NHS Breast Screening Programme is not designed for detection of implant rupture but rather the early detection of breast cancer. The breast screening program has published a leaflet for women with breast implants. This leaflet 'Breast Implants and Breast Screening' is available from local breast screening units.

References
US Institute of Medicine, Safety of Silicone Breast Implants, National Academy Press Washington DC 1999.
Dominic S Raso et al, Elemental Analysis and Clinical Implications of Calcification Deposits Associated with Silicone Breast Implants, Annals of Plastic Surgery Vol 42 p117-123.
Guidance on Screening and Symptomatic Breast Screening, Board of Faculty of Clinical Radiology.
S J Hoshaw et al, Breast implants and cancer: Causation, delayed detection and survival, Plastic and Reconstructive Surgery 2001 107, 1393-1408.

Association with anaplastic large cell lymphoma
In January 2011 the USA's Food and Drug Administration (FDA) published a Safety Communication entitled ‘FDA Medical Device Safety Communication: Reports of Anaplastic Large Cell Lymphoma (ALCL) in Women with Breast Implants’ (external link).

In a thorough review of scientific literature published from January 1997 to May 2010, the FDA identified 34 unique cases of ALCL in women with breast implants throughout the world. The FDA’s adverse event reporting systems also contains 17 reports of ALCL in women with breast implants. This is a very small fraction of the 5-10 million women who have received breast implants worldwide. Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin’s lymphoma (NHL), a cancer involving the cells of the immune system. It is a very rare tumour in the breast, accounting for less than 1% of all breast malignancies. To date there have been no corresponding reports of this disease association to the MHRA. The MHRA encourages all surgeons to report all adverse incidents, including cases of ALCL, to the adverse incident centre (aic@mhra.gsi.gov.uk). The MHRA will review any evidence that comes to light and take appropriate action as needed. There is no indication for any routine action in the form of explantation or regular radiological examination including MRI. Women should be advised to self examine and consult their medical practitioner if they notice any changes in the breast or have any concerns.

Effect on children of women with breast implants (including breast feeding)
There have been a number of anecdotal reports that children born to mothers with a silicone gel breast implant (SBI) have developed swallowing difficulties, irritability, non-specific skin rashes, fatigue and a constellation of symptoms similar to those occurring in women with a SBI. Patient self help groups have collected information from women phoning in with their own concerns and who have been questioned about health problems in their children. There has also been a considerable media interest in the potential harmful effects of SBIs on children’s health. Further details (22Kb).