Breast Implants: Deadly Devices
Breast Implants: Deadly Devices
The Long Read: This post is an excerpt from our upcoming book on medical devices and their harmful and deadly effects. At times it's heavy going on the facts, so we recommend reading in several goes.
Silicone breast implants present a sorry tale of regulatory negligence, bad evidence, criminality, and a failure to learn lessons. Forty years after concerns emerged - for what is mainly a cosmetic procedure - many questions remain about how to reduce harms and ensure patient safety.
A brief history of breast implants
In the 1890s, paraffin was injected into breasts to increase their size. But the paraffin leaked, and the technique was abandoned. In the 20s and 30s, surgeons tried transferring fat – also not a good idea. And in the 50s, cartilage, wood, and even glass balls were used – the side effects were disastrous. In 1962, Timmie Jean Lindsey, in Houston, Texas, was the world’s first to undergo breast augmentation surgery using silicone implants.
As a mixture of compounds, silicone’s properties vary, becoming more or less stiff and stickier depending on the stress applied. Over time, many design changes have occurred to make implants that maintain their shape over the long term while preventing tightening, squeezing and rupture. First-generation implants used a thick, smooth silicone encased in an envelope made with seams. In addition, they used polyurethane-coated foam, which degraded and released 2-toluene diamine, a known carcinogen in animals; the FDA asked the manufacturer to supply safety information. But, the manufacturer removed them from the market, which negates the need to provide safety information. The manufacturers knew that you could place version two on the market with a few tweaks to the original, and no questions would be asked. Remove the polyurethane-coated foam, and there’s nothing to see.
However, In the 1980s, concerns over silicone breast implant increasing the risk of cancer, connective-tissue diseases, and various autoimmune diseases emerged. Then, in 1988, an American consumer interest group reported silicone gel implants could cause cancer in rats. [1] By then, more than two million American women had received them. The US FDA concluded the results in rats were irrelevant to women, but the anxieties caused by the media frenzy led thirty thousand US women to have their implants removed.
The FDA tightens the regulatory requirements
In 1988, the FDA’s Breast Implant Advisory Panel classified silicone implants as class III devices - putting them in the highest risk class. Manufacturers now had to provide clinical trial evidence proving safety and effectiveness through the Premarket Approval route (PMA). Confusingly, implants were still allowed through the less robust 510(k) process. Briefly, the 510(k) pathway allows the use of equivalence - my device is similar to one already on the market, and because that’s safe, so is our device. It removes the need for clinical trial evidence and emphasises laboratory-based biological testing of the implants.
The FDA issued a final deadline of 1991 for manufacturers to submit the clinical trial evidence. [2] The submitted Evidence contained insufficient data to meet the approval requirements of PMA. Therefore, the FDA’s advisory panel met again, and ‘despite the lack of data’ unanimously recommended the implants stay on the market pending further results.
In December 1991, a California jury awarded $7.3 million to Marianne Hopkins. She underwent a double mastectomy; she developed mixed connective tissue disease from her silicone implants. The case documents show the manufacturer, Dow Corning, was aware their implants were leaking, but they did nothing to provide long-term safety data. These second-generation implants used thinner, seamless shells to try and reduce capsular contracture - changes that made them more prone to leakage. The court documents, although under seal, were leaked to the media. While they contained no new safety concerns, they dramatically affected the decision of the FDA’s commissioner, Dr David Kessler. On 6 January 1992, he called for a voluntary delay for silicone implants because of the possible link with autoimmune diseases. He announced a 45-day voluntary moratorium and restricted use to clinical trials. A tidal wave of U.S. lawsuits ensued.
Kessler said, ' thirty years after silicone breast implants appeared on the market, the list of unanswered questions about their safety remains long.’ There was a lack of evidence for rupture rates, limited information on the chemicals that leak into the body, and knew little about an implant's life expectancy. Although they didn’t come out and say it directly, the FDA admitted they knew very little - and in some cases nothing - about breast implants at the time of approval. [3]
While Kessler was putting in place a moratorium on the use of breast implants, the UK Department of Health arrived at the opposite conclusion. No link existed between silicone breast implants and connective tissue disease - [4] nothing to see here then. Regulators were at odds with each other and, consequently, were confused about what to do; they flip-flopped between bans and approvals.
France, for instance, banned the implants only to overturn the ban within three years. The UK’s Chief Medical Officer set up an Independent Review Group in response to concerns the Minister for Health raised. Baroness Jay was worried that many women with breast implants had severe medical problems. However, evidence from systematic reviews supported no link with a range of immune disorders. The British Medical Devices Agency concluded the risks were no more significant than for any other type of implant. However, two implants were withdrawn: lipid-filled breast implants and hydrogel-filled breast implants. [5]
In 1992, The Lancet reported a series of silicone gel breast implant patients who had antinuclear antibodies. [6] Antibodies are a normal part of the body's immune system and help fight infections. They do this by recognising foreign proteins. However, sometimes antibodies make mistakes and identify the body's proteins as foreign. We call these autoantibodies. Their presence indicates systemic autoimmune disorders that can be disabling as they can affect multiple tissues and organs throughout the body.
The US Institute of Medicine reviewed saline-filled and silicone gel-filled breast implants in 1999. They concluded there was insufficient evidence to establish implants caused autoimmune diseases. However, the Institute considered breast implants' main safety concerns were rupture, pain, capsular contracture, disfigurement, and severe infection. [7]
By 2000, a New England Medicine Journal meta-analysis of 20 observational studies reported no associations between implant and rheumatoid arthritis and various autoimmune diseases. [8] In March of the same year, the FDA Advisory Panel recommended PMA approval for two saline-filled breast implants, and by 2006 silicone gel-filled implants were back, effectively ending a 14-year ban on their approval. [9] The FDA’s actions saw a dramatic increase in breast augmentations, which became the number one cosmetic procedure in 2006. Silicone implants use grew from 35% of all implants in 2007 to more than 75% by 2014. [10]
For approval, the FDA now required a minimum of three years of data for silicone gel breast implants and two years for standard saline-filled breast implants. Once on the market, the studies were supposed to follow women for ten years after receiving the implants. As an example, Allergan and Mentor were asked to follow 40,000 women with implants for ten years after the implants. More than 40,000 women were enrolled, but by 2011, large numbers were lost to follow-up. [11] The FDA also recommended scanning every three years after the first implant and then every two years. These additional costs exceeded the implant surgery cost and weren’t covered by health insurance - the scans didn’t happen. [12]
The PIP Implant scandal
Although evidence for implant harm was accumulating, what occurred with the PIP implant highlighted the shocking loopholes in the manufacturing processes that put patients at substantial risk. In 1991, Jean-Claude Mas, a former butcher turned medical sales representative for Bristol-Myers Squibb, and Henri Arion, a plastic surgeon who introduced breast implants to France in the 60s, launched the Poly Implant Prothese (PIP), which went on to produce over two million sets of silicone breast implants.
PIP received 510(k) approval for their saline-filled breast implant in 1996. [13] The FDA allowed the saline implant to be approved without clinical trial evidence because these were available before 1976 and assumed safe unless proven otherwise. But as stated, in 2000, due to safety concerns, the FDA required all implant (saline and silicone) manufacturers to submit evidence for PMA approval before marketing their products. PIP's application was rejected. The clinical trial data did not include enough patients followed up for long enough to demonstrate safety. [14]
In May, the FDA began inspecting PIP’s manufacturing site in La Seyne Sur Mer, France. They found numerous manufacturing deficiencies and at least eleven deviations from good manufacturing practices. As a result, PIP stopped selling its saline and silicone implants in the US. Despite the FDA’s posting a warning letter stating PIP’s failure to investigate problems and report more than 120 French complaints to the FDA, European regulators did nothing. The FDA sent a copy of their letter to Mas but not the regulators, and Mas covered it up.
The loss of US revenues meant Mas had to cut costs drastically. He manufactured the implants using a non-approved industrial-grade silicone, cutting the price by nearly 90% (estimates suggest they saved $1.6 million in production in one year alone). [15] The protective outer skin of the implant was also replaced with lower-grade silicone. These changes occurred sometime in 2001. Predictably implants began rupturing at much higher rates: more than double the industry average.
In 2010 the French medical safety agency recalled the implants and advised 30 000 women to have their implants removed. Then, in March, inspectors found six discarded plastic containers of Silopren, designed for industrial use; they contained nearly nine tonnes of the silicone. Police were informed, and within two weeks of the inspection, the company was closed and went into liquidation.
In a radio interview, Mas admitted he had manufactured the implants with industrial-grade silicone gel to save money without regulatory approval. By then PIP had sold more than 300,000 silicone gel implants in 65 countries; the damage had been done.
Cracks in the European regulatory processes kept PIP products on the market. Once approved, there was no requirement for unannounced checks of the implant contents or chemical composition tests. Annual audits of the manufacturers by the Notified Body, TUV Rheinland, did not do any on-site tests. However, the Notified Body was cleared of wrongdoing by the French high courts, which reported that "TUV Rheinland could not have detected the fraud committed by PIP with the tools granted to certification organisations under current regulations." In later chapters, we’ll discuss notified bodies further, their shortcomings, and the regulatory processes' holes.
The European regulatory system for devices is exceedingly lax in its approach to safety. As further demonstrated by a 2016 study on Silicone breast implants - commissioned by the Dutch Health and Youth Care Inspectorate - that found deficits in the laboratory tests done by manufacturers. The study evaluated ten technical files of breast implant manufacturers and found that while all performed mechanical implant testing and found no problems with biocompatibility and cytotoxicity testing (some good news then), there were missing tests for irritation, sensitisation, and implantation tests - all requirements for European approval.
Sensitisation tests see if the implant material initiates a sensitising effect or an allergic reaction. But because they often - if not always - involve small animals (e.g., mice), it is impossible to evaluate their sensitivity effects in relation to humans. Furthermore, the PIP Implant post-marketing surveillance studies were inadequately reported, particularly the level of detail required for safety and performance. [16] Also, complete and correct technical files were often deficient or absent, despite being an essential part of the approval process for ensuring patient safety in the European Union.
The UK’s Department of Health responded to the PIP implant scandal at the time by reporting they were safe! [17] They said there was insufficient evidence to determine the safety problems. Rupture rates in France were reported to be five per cent, whereas the UK regulator, the Medicines and Healthcare Regulatory Authority, said they were only one percent.
The UK’s Chief Medical Officer, Dame Sally Davies, said, "Women with PIP implants should not be unduly worried. We have no evidence of a link to cancer or an increased risk of rupture. If women are concerned, they should speak to their surgeon". Removing the implant "carries risks in itself.” [18] This is despite the MHRA receiving 269 adverse incident reports as far back as 2001-02. [19] Andrew Lansley, the Health Secretary, was so concerned that he ordered another review when the media reported rupture rates as high as eight per cent. As part of his defence, Mas pointed out in his radio interview that Britain had not followed France’s lead.
The MHRA did, however, confirm the European implants contained non-medical grade silicone and did not rule out that some of the implants were toxic. It took a further six years to bring Mas to justice. He appealed against his sentence, which the High courts in France rejected, and was eventually sentenced to four years in jail and fined €75,000.
In 2010, PIP implants were withdrawn from the market. The actual numbers affected might never be known. Thousands received Rofil M-implants, which had an agreement to buy implants from PIP, and TiBREEZE breast implants made by a German company were affected by the PIP scandal. [20] The NHS think About 47,000 British women had PIP implants, and most still have them; if they were done privately, they won’t pay for their removal on the NHS. [21]
Anaplastic large cell lymphoma (ALCL) is rare, with an incidence somewhere between 1 in 50,000 and 1 in 300,000.
In 2011, the UK MHRA initiated a medical device alert after reports of 14 cases of ALCL. In the same year, the FDA also issued a safety communication that reported women with breast implants had a small but increased risk of developing a form of cancer called Breast implant Anaplastic Large Cell Lymphoma (BIA-ALCL) in the scar capsule adjacent to the implant. In 2016, the World Health Organization designated BIA-ALCL a T-cell lymphoma that can develop following textured surface breast implants. [22,23]
A Dutch study reported 11 women eleven women with breast-induced ALCL. All had received breast implants for cosmetic reasons. [24] In 2017, a systematic review reported 95 cases of ALCL. The mean time to diagnosis was ten years after implant placement. The first documented case was in 1997; although rare, it is increasing. [25] In 2017, a further 55 cases were reported to the FDA, taking the total to 414, with nine deaths. By 2019 The American Society of Plastic Surgeons reported 779 cases and 33 deaths. [26]
In July 2020, Allergan lost its safety licence to sell its textured implants in Europe. [27] It was the French regulator that issued the warning and withheld the CE safety mark. In contrast, the FDA kept some of them on the market. Not the first time we’ve seen regulatory discrepancies. The PIP implant scandal had likely made the French hyper-aware of the problems with implants and more likely to intervene. Not the British, though; the MHRA’s less stringent approach meant “there is currently no evidence of an increased risk to patients, and there is no need for people who have Allergan breast implants to get them removed or have any additional clinical follow-up.’ Yet, in October 2019, the FDA had already recommended breast implant manufacturers include a boxed warning on the packaging about the risks and complications that might need surgery and the development of a rare, sometimes fatal cancer. This begs the question of what would constitute a signal of harm in the UK.
By the end of 2021, the UK regulator had received 87 reports of confirmed BIA-ALCL (six of the procedures occurred outside of the UK). Current UK advice states, “clinicians have a legal obligation to discuss the potential risk of BIA-ALCL when seeking informed consent of new patients, and with any patient returning for review of their breast implants.” [28]
In 1993, The UK promised a National Breast Implant Registry. [29] However, NHS Digital launched the Breast and Cosmetic Implant Registry in 2016 - 29 years after it was first promised. It takes roughly ten years for the problems to emerge, so in 2026 we may see the harms and a more vigilant approach to safety in the UK. However, we’re not holding our breath.
Will the implant controversy go away?
A population-based study in 2018 in Israel showed an association between silicone-based implants and autoimmune and rheumatic disorders. The study matched 24,651 women with breast implants and 98,604 without. Adjusting for age, socioeconomic status, smoking status, and breast cancer history, they found women with implants had a 45 percent greater chance of being diagnosed with at least one autoimmune or rheumatic disorder.
Rupture leads to the release of silicone into the body. But a process referred to as ‘gel bleed’ is more likely the problem as it occurs when microparticles of silicone slowly leak into the body from intact implants. The implant shell is semipermeable, allowing silicone passage into the body. Consequently, silicone has been found in blood vessels, multiple tissues, and brain samples at autopsy. [30] Earlier research regarded silicone as biologically inert; however, silicone induces various immunological effects. Furthermore, a systematic review of 32 studies found possible associations between silicone gel implants, rheumatoid arthritis and Sjögren syndrome (an autoimmune disease that affects parts of the body that produce tears and saliva). [31] The implant controversy has been ongoing for 40 years - it seems likely to continue.
In August 2022, the FDA received 1,130 reports of BIA-ALCL and 953 related to Allergan implants. The FDA issued a further safety warning in September of the same year after receiving 12 squamous cell carcinoma reports that were distinct from BIA-ALCL. The agency also knew of nearly 30 cases of various lymphomas in the capsule around the implant. [32]
So, how deadly are breast implants?
A systematic search of the US Manufacturer and User Facility Device Experience (MAUDE) database in 2019 identified 50 possible implant-related deaths. Nearly half (42%) were breast implant-associated anaplastic large cell lymphoma. The authors considered that 23 of the 50 deaths were genuinely caused by breast implants. [33] In August 2020, the FDA reported 36 patient deaths relating to BIA-ALCL, three new deaths since the early-July 2019 update. [34] There are also sporadic reports of ‘Botched Breast Enhancement Surgery’ deaths. [35] Some evidence suggests that breast augmentation adversely affects the survival of women subsequently diagnosed with breast cancer [36] and increases the risk of suicide. [37]
Outcomes are worsened by the medical tourism industry, which is on the increase. For example, a systematic review of 17 observational studies of cosmetic tourism for breast augmentation found reports of sepsis, irreversible hypoxic brain injury, and death in the studies.
The global cosmetic implants market is expected to surpass $20 billion by 2030 - breast implants will likely be a $3 billion share of this market.
If you've made it this far we reckon you’ll be able to form your own conclusions. Unfortunately, the absence of high-quality evidence, regulatory dissonance and the lack of registries - until recently - means we will see new harms and safety messages. In the next chapter we’ll look at the problems with Essure and the further failings of medical device regulation.
References
1. Special To the New York Times. Silicone Implants Tied To Cancer in Test Rats. N.Y. Times Published Online First: 10 November 1988 .https://www.nytimes.com/1988/11/10/us/silicone-implants-tied-to-cancer-in-test-rats.html
2. FDA Breast Implant Consumer Handbook – 2004.” Center for http://www.professor-graf.de/tl_files/professor-graf/Infos/Aesthetik/fdabreastprosthesis.pdf
3. The Basis of the FDA’s Decision on Breast Implants. N Engl J Med 1992;326:1713–5.
4. Silicone Breast Implants: An Oncologic Perspective | Cancer Network. http://www.cancernetwork.com/breast-cancer/silicone-breast-implants-oncologic-perspective
5. The Committee Office, House of Commons. House of Commons - Health - Minutes of Evidence. The Stationery Office Ltd. 2001.https://publications.parliament.uk/pa/cm200001/cmselect/cmhealth/308/1032213.htm
6. Antinuclear autoantibodies in women with silicone breast implants. Lancet 1992;340:1304–7.
7. Institute of Medicine, Committee on the Safety of Silicone Breast Implants. Safety of Silicone Breast Implants. National Academies Press 2000.
8. Meta-analyses of the relation between silicone breast implants and the risk of connective-tissue diseases. N Engl J Med 2000;342:781–90.
9. Premarket Approval (PMA). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm?id=P020056 (accessed 13 Nov 2018).
10. Working Toward a Solution: The Unanswered Questions About Silicone Gel Breast Implants. Ann Intern Med 2016;164:201–2.
11. https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM071233.pdf
12. FDA approves silicone breast implants 14 years after their withdrawal. BMJ : British Medical Journal 2006;333:1139.
13. The saga of Poly Implant Prosthese breast implants. BMJ 2012;344:e306.
14. Insight: FDA warned PIP on breast implant safety in 2000. U.S. 2011.https://www.reuters.com/article/us-breastimplants-fda-idUSTRE7BQ03M20111228
15. Special Report: The French breast implant scandal. U.S. 2012. https://www.reuters.com/article/us-breast-implants-mas-idUSTRE8110WY20120202
16. Appeal court clears inspectors in French breast implants case | Healthy Living Magazine. https://www.healthylivingmagazine.us/Articles/11338/
17. Department of Health, Care S. Department of Health statement on breast implants and response to expert group report. GOV.UK. 2012. https://www.gov.uk/government/news/department-of-health-statement-on-breast-implants-and-response-to-expert-group-report (accessed 12 Nov 2018).
18. . France, UK issue clashing advice on breast implants. U.S. 2011. https://www.reuters.com/article/us-breast-implants-idUSTRE7BM14420111224
19. The PIP scandal: an analysis of the process of quality control that failed to safeguard women from the health risks. J R Soc Med. 2013 May;106(5):173-7. doi: 10.1177/0141076813480994.
20. The ‘PIP scandal’ – Complications in Breast Implants of Inferior Quality: State of Knowledge, Official Recommendations and Case Report. Geburtshilfe Frauenheilkd 2012;72:243.
21. https://www.nhs.uk/conditions/pip-implants/
22. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016 May 19;127(20):2375-90. doi: 10.1182/blood-2016-01-643569. Epub 2016 Mar 15.
23. Anaplastic large cell lymphoma occurring in women with breast implants: analysis of 173 cases. Plast Reconstr Surg. 2015 Mar;135(3):695-705. doi: 10.1097/PRS.0000000000001033.
24. Anaplastic large-cell lymphoma in women with breast implants. JAMA. 2008 Nov 5;300(17):2030-5. doi: 10.1001/jama.2008.585.
25. A Systematic Review. JAMA Surg. 2017 Dec 1;152(12):1161-1168. doi: 10.1001/jamasurg.2017.4026.
26. https://medicine.wustl.edu/news/surgeon-weighs-in-on-textured-breast-implants/
27. https://www.simonleeplasticsurgeon.co.uk/articles/textured-breast-implants/
28. https://www.gov.uk/guidance/breast-implants-and-anaplastic-large-cell-lymphoma-alcl#full-publication-update-history
29. Breast implant women to be placed on register: Health department says. The Independent. 1993.http://www.independent.co.uk/news/uk/breast-implant-women-to-be-placed-on-register-health-department-says-record-of-surgery-is-only-a-1492926.html
30. Gel Bleed and Rupture of Silicone Breast
31. Balk EM, Earley A, Avendano EA, et al. Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med 2016;164:164–75.
32. https://www.fda.gov/medical-devices/safety-communications/breast-implants-reports-squamous-cell-carcinoma-and-various-lymphomas-capsule-around-implants-fda
33. Death by Implants: Critical Analysis of the FDA-MAUDE Database on Breast Implant-related Mortality. Plast Reconstr Surg Glob Open. 2019 Dec 26;7(12):e2554. doi: 10.1097/GOX.0000000000002554.
34. https://www.fda.gov/news-events/press-announcements/fda-updates-analysis-medical-device-reports-breast-implant-illness-and-breast-implant-associated
35. https://people.com/health/19-year-old-dies-after-botched-surgery/
36. Breast cancer detection and survival among women with cosmetic breast implants: systematic review and meta-analysis of observational studies BMJ 2013; 346 :f2399 doi:10.1136/bmj.f2399
37. Manoloudakis N, Labiris G, Karakitsou N, Kim JB, Sheena Y, Niakas D. Characteristics of women who have had cosmetic breast implants that could be associated with increased suicide risk: a systematic review, proposing a suicide prevention model. Arch Plast Surg. 2015 Mar;42(2):131-42. doi: 10.5999/aps.2015.42.2.131. Epub 2015 Mar 16.
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