With the US FDA reporting new types of cancers in scar tissue around breast implants, it has bluntly warned both medical practitioners and potential patients: this is an emerging issue and our understanding is evolving.
Director of Cosmetic and Plastic Surgery at Macquarie University’s Faculty of Medicine and Health Sciences
Breast augmentation is one of the most popular cosmetic procedures around the globe: more than 1.862 million procedures were recorded worldwide in 2018 (down 9.5% to 1.624 million in 2020 during Covid restrictions), according to the annual survey of the International Society of Aesthetic Plastic Surgeons (ISAPS).
In the US, breast augmentation continues to be the most common cosmetic procedure. ISAPS reported over 313,000 procedures performed in 2018 – a huge 48% increase since the year 2000.
In Australia, the latest figures record 20,000 breast augmentation surgeries annually (75% cosmetic and 25% reconstructive).
The issue of implant-related complications has been widely debated ever since the US Federal Drug Administration (FDA) approved the use of breast implants in 1962.
The Australian Therapeutic Goods Administration (TGA) confirmed it would convene a meeting of its breast implant expert working group during October to discuss the FDA’s September Safety Communication reporting ‘cancers, including squamous cell carcinoma (SCC) and various lymphomas, in the scar tissue that forms around breast implants’.
But with the FDA emphasising these latest lymphomas ‘are not the same’ as those described in its previous Safety Communications as Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), patients considering implants now need to assess the potential health risks associated with 3 distinct areas of concern:
- SCC and other lymphomas;
- specific BIA-ALCL;
- long-debated, wide-ranging and multi-factored Breast Implant Illness (BII).
SCC and other lymphomas
While alerting both potential implant patients and health professionals about cancers, including squamous cell carcinoma (SCC) and various lymphomas in the tissue around implants, the FDA also emphasised it:
- is aware of less than 20 cases of SCC and less than 30 cases of various lymphomas in the capsule around the breast implant; and
- has received 10 medical device reports (MDRs) about SCC related to breast implants and 12 MDRs about various lymphomas related to breast implants.
Professor Anand Deva, Director of Cosmetic and Plastic Surgery at Macquarie University’s Faculty of Medicine and Health Sciences, confirmed that among this group in Australia he is aware of one case of SCC ‘who is still alive and currently cancer-clear’ and two further cases of B-cell lymphomas.
But he warned that, while the FDA’s latest Safety Communication is an important warning to be on the lookout for further similar cases, with the overall current international totals so small, it is impossible yet to determine whether these cancers are indeed implant-related – or what else may be linked to their causation?
Professor Deva said the most important message, for both patients and practitioners, was the ‘need to watch carefully for any new potential instances’.
He emphasised: ‘The primary lesson is that anyone with implants needs to ensure they undertake regular check-ups with their doctor/ surgeon as a priority.
‘I advocate the importance of an annual check specifically with the doctor who inserted the implant.
‘While women, especially over 40, are already advised to have a mammogram every two years, for women with implants I’d advocate both mammograms and an ultrasound – and it’s incorrect that you can’t or shouldn’t have a mammogram if you have implants.’
Professor Deva explained that ‘patients need to understand there is a lifelong risk with an implant.
‘So, as well as undertaking the important precaution of annual check-ups, they will then also ensure they are kept aware of anything new that emerges following any further warnings about SCC and/or other potential lymphomas.
‘In addition, by talking to and checking annually with their doctor, the patients themselves become positively empowered.’
What we know about BIA-ALCL
The US FDA noted in its September Safety Communication that the latest lymphomas reported are not the same’ as those described in previous FDA Communications as BIA-ALCL.
The FDA has been separately collecting and evaluating information about BIA-ALCL since 2011.
In 2016 the World Health Organisation (WHO) designated BIA-ALCL a ‘T-cell lymphoma that can develop following breast implants’ – but noted the exact number of cases remained ‘difficult to determine due to significant limitations in world-wide reporting and lack of global breast implant sales data’.
Subsequently, the FDA undertook an in-depth review of post-approval study data and in 2019 highlighted its ‘many important breast implant concerns’ in a public advisory committee meeting, accompanied by publication of a detailed Q&A regarding BIA-ALCL on its website.
It noted:
- BIA-ALCL is not breast cancer – it is a type of non-Hodgkin’s lymphoma (cancer of the immune system);
- in most cases it is found in the scar tissue and fluid near the implant (not in the breast tissue itself), but in some cases it can spread throughout the body;
- this cancer is serious and can lead to death, especially if not treated promptly – in most cases it is treated successfully with surgery to remove the implant and surrounding scar tissue;
- the main symptoms are persistent swelling, presence of a mass or pain in the implant area – these may occur well after the surgical incision has healed, often years after implant placement;
- the risk of BIA-ALCL is higher for textured surface implants versus smooth surface implants;
- the type of implant fill (silicone versus saline) does not appear to be a risk factor for BIA-ALCL.
Also in 2019 the WHO recognised BIA-ALCL as a ‘unique form of ALCL that can develop following implantation of a breast implant’.
As a result:
- Health Canada announced it would update its safety review of breast implants.
- The French National Agency for Medicines and Health products Safety (ANSM) announced its decision to withdraw ‘macro-textured’ breast implants and breast implants with polyurethane- coated surfaces marketed in France.
- Australia’s TGA announced 8 types of ‘macro’ and ‘micro’ textured implants would be recalled and banned for 6 months while their manufacturers addressed ‘a number of safety and performance concerns’ and the TGA completed an assessment of textured breast implants in Australia or exported from Australia.
Subsequently in 2020 the TGA cancelled several types of breast implant devices from the Australian Register of Therapeutic Goods (ARTG).
In addition, the TGA hosted 2 discussion panels in 2020: one to discuss BIA-ALCL and breast reconstructive surgery and another to discuss BIA-ALCL and breast augmentations. These were recorded and have been made available as webinars to view online (a current link is available on the TGA website).
The webinars provide information for consumers on issues including clinical guidelines, essential follow-up, consent processes, regulatory changes, financial issues, and complications and their management.
BIA-ALCL numbers falling since 2019
Professor Anand Deva explained that 2019 was a big year in confronting potential BIA-ALCL issues:
‘Allergan recalled un-implanted, macro-textured breast implants and tissue expanders and, from that point, the number of cases reported during Covid dropped off.
‘The good news is there have been no signs of a rebound in BIA-ALCL numbers since then.
‘So I’m cautiously optimistic that the rate of new cases has indeed slowed down and may continue to fall, since we’d already moved away from textured implants.’
Professor Deva summed up:
‘At the moment, as a result of ongoing scientific study and industry research both locally and internationally, plus TGA oversight and regulators around the world all working together, the outlook regarding BIA-ALCL is now a ‘good news’ story.’
He predicted that with both patients and their doctors aware of the need to regularly and diligently check for any early signs of trouble, the rate of new BIA-ALCL cases ‘should continue to fall.’
Professor Deva noted that, while the peak time for potential BIA- ALCL ‘trouble’ is after 7-8 years, the message to consistently monitor for any unusual inflammation or similar disturbance is out there now, following extensive positive educational work with cosmetic clinicians, general practitioners and the whole industry.
In summary, following the move away from textured implants and with only the 4 previously recorded deaths from 115-120 total cases in Australia – and a worldwide total of around 1,500 cases (arising from almost 2 million implant surgeries each year over the past decade) – Professor Deva optimistically observed: ‘I’m not particularly worried about increasing cases of BIA-ALCL anymore.’
300 women in Australian BII/SSBI Study
For over 50 years, ‘Breast Implant Illness’ (BII) has been a term used by women who have breast implants and self-identify to describe a wide variety of symptoms including fatigue, chest pain, hair loss, headaches, chills, photosensitivity, chronic pain, rash, body odour, anxiety, brain fog, sleep disturbance, depression, and neurologic and hormonal issues which they feel are directly connected to their saline or silicone, textured or smooth implants.
The rise of patient advocacy and communication through social media has triggered an increase in patients reporting BII symptoms; by the start of 2021, one BII Facebook group had more than 130,000 members.
However, while the relationship between breast implants and systemic disease has been reported and debated since the 1960s, numerous studies of BII have neither definitively supported nor refuted its existence – and there has been no formal medical diagnosis.
As part of a major ongoing study to address this issue, Professor Deva and a group of academic and surgical experts in this field, have spent the past 3 years overseeing a collaborative study to specifically shed light on potential facts and myths surrounding BII.
Professor Deva explained:
‘We now call this area ‘Systemic Symptoms associated with Breast Implants’ (SSBI) and our local study involves over 300 Australian women. In addition, we are sharing our research and results with a similar study group in the US.’
He revealed that, for women who ‘have had their implants removed, we have noted marked drops in both the frequency and magnitude of their complaints after 6 months.
‘So now the primary aims for our study are to ask: Firstly ‘why’? And then secondly ‘is that drop-off sustained over time’?
‘So time will be the big test here.’
Significant ‘anxiety and depression’
In examining and assessing potential triggers for the many and varied ailments postulated to have been associated with BII/SSBI, Professor Deva confirmed: ‘Implants no doubt cause some chronic inflammation at the site.
‘But there are also many other causes of inflammation in the body (immune system reactions to injury or infection). So the key issue is to determine what may or may not be specifically related to the implants.’ Among other elements, the study has closely examined (among other factors):
- each patient’s implant, capsule and peri-implant tissues to delineate the presence of pro-inflammatory substances and their subsequent effect on local tissues;
- detection and characterisation of the microbiome on these implants and capsules;
- genetic sequencing to look for patterns of gene mutations and HLA-type (the immune system uses HLA ‘protein markers’ to recognise which cells belong in a body and which do not) that predispose to development of auto-immune and other systemic disease; and
- blood screening for auto-immune disease markers.
Professor Deva summed up: ‘After seeing and listening to lots of patients with SSBI issues, I don’t think we can discount their concerns.
‘I have observed first-hand the very significant levels of associated anxiety and depression being exhibited among these women. So simple denial of SSBI can be
a mistake.
‘The key issue for us has become: are the implants the ‘driver’ of their medical complaints or a ‘secondary effect’?’
Australian breast device register
The Federal Government established the Australian Breast Device Registry (ABDR) in 2015 to:
- identify and report on possible trends and complications associated with breast device surgery;
- track the long-term safety and performance of implantable breast devices;
- identify best surgical practice and optimal patient health outcomes.
The ABDR – independently managed by Monash University and endorsed by Australian surgical societies representing plastic and reconstructive surgeons, cosmetic surgeons and general breast surgeons – is the central repository of data for all breast device issues, including BIA-ALCL.
The ABDR collects comprehensive information about breast implants, breast tissue expanders and dermal mesh. It currently holds breast device details for over 79,500 patients provided by more than 600 contributing surgeons from public and private hospitals and day surgeries in all states and territories.
The 2020 Annual Report noted:
- The overwhelming majority of breast device surgery reported to the ABDR occurs in private hospitals, which perform 99% of all cosmetic device procedures and 76% of reconstructive device procedures in Australia.
- 73% of registered patients had cosmetic device procedures, with the remainder reconstructive device procedures (with 6.5% not stated).
- There has been a significant decline of approximately 50% in the use of textured implants for reconstructive surgery over the last 5 years.
- The most common complications associated with ‘reconstructive procedures’ were capsular contracture (34%), device malposition (24%) and device rupture (18%); all-cause revision incidence at 5 years was 19% for risk-reducing procedures, 16% for post-cancer procedures and 13% for developmental procedures; polyurethane devices had a higher revision incidence compared to textured and smooth implants.
- The most common complications associated with ‘cosmetic procedures’ were capsular contracture (36%), device rupture (23%) and device malposition (19%); all-cause revision incidence at 5 years was 5%, and revision incidence due to complications was 3%.
- Data from the Macquarie University team included 112 confirmed breast implant associated anaplastic large cell lymphoma (BIA-ALCL) cases between 2007 and 2019.
- ABDR-reported cases showed variation in the duration of the implanted device, with the most common duration being 8-9 years from insertion to the BIA-ALCL diagnosis. AMP
FDA warning: ‘cell cancer around implants’
In September the US Federal Drug Administration issued a new Safety Communication ‘informing the public about reports of cancers, including squamous cell carcinoma (SCC) and various lymphomas, in the scar tissue (capsule) that forms around breast implants’.
The FDA noted these latest lymphomas reported ‘are not
the same’ as those described in previous FDA Communications as Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).
The FDA added that, at 1 September 2022, it:
- is aware of less than 20 cases of SCC and less than 30 cases of various lymphomas in the capsule around the breast implant; and
- has received 10 medical device reports (MDRs) about SCC related to breast implants and 12 MDRs about various lymphomas related to breast implants.
Most importantly, the FDA warned medical practitioners and potential patients: ‘This is an emerging issue and our understanding is evolving. While the FDA believes occurrences of SCC or various lymphomas in the capsule around the breast implant may be rare, health care providers and people who have or are considering breast implants should be aware that cases have been reported to the FDA and in the literature.’
The FDA added that while ‘currently the incidence rate and risk factors… are unknown’, there have been literature reports for both textured and smooth breast implants, and for both saline and silicone breast implants; additionally in some cases people were diagnosed after years of having breast implants – with reported signs and symptoms including swelling, pain, lumps or skin damage.
Importantly the FDA Safety Communication contains this patient warning: ‘Breast implants are not lifetime devices.
‘The longer you have implants, the more likely it will be for you to have them removed or replaced.’
TGA response: SCC risk ‘extremely rare’
Following the latest US FDA Safety Communication, Australia’s Therapeutic Goods Administration (TGA) responded that ‘the risk of squamous cell carcinoma (SCC) and lymphomas occurring in the tissue around breast implants appears to be extremely rare’.
The TGA noted: ‘At this time, there is not enough information to say whether breast implants cause these cancers or if some implants pose higher risk than others’.
While symptoms of these conditions ‘can include swelling, pain, lumps or skin changes, it is important to note that these symptoms can also reflect other breast health issues’.
The TGA emphasised ‘medical experts do not recommend breast implant removal in patients without symptoms or other abnormality’.
The TGA said it is monitoring the occurrence of the disease in Australia and is in communication with other international regulators and experts in Australia.
The TGA also encouraged any patients with concerns to visit its ‘Report a problem or side effect’ webpage and complete the online form to describe any problems they may be experiencing.
Meanwhile the TGA continues to regulate breast implants in Australia as ‘high risk medical devices’ – meaning it evaluates these products for safety, quality and performance before they can be used in surgery.
The TGA also works closely with the Australian Breast Device Registry (ABDR) ‘to monitor the ongoing safety and performance of breast implants’. (See accompanying box re ADBR)
BIA-ALCL: TGA ‘info for consumers’
Australia’s Therapeutic Goods Administration (TGA) has published a ‘BIA-ALCL: Information for Consumers’ summary, including these Questions and Answers.
Q: What is breast implant associated cancer (BIA-ALCL)?
A: Also known as breast implant associated anaplastic large cell lymphoma (BAI-ALCL), it is a rare cancer of the immune system.
It is not breast cancer, which forms from cells in the breast, but instead a cancer that grows in the fluid and scar tissue that forms around a breast implant; less commonly, it can take the form of a lump in the breast or a lump in the armpit.
BIA-ALCL has occurred as soon as one year after the operation and as late as 37 years after the operation. The average time to diagnosis is within 8 years.
Q: Who can get BIA-ALCL?
A: All reported cases in Australia involve patients who have had a textured implant.
Based on current evidence, experts do not think BIA-ALCL is related to either the contents (saline/silicone) or shape (round/teardrop) of the implant.
BIA-ALCL is rare: a review by the TGA found between 1-in-2,500 and 1-in-25,000 people with implants are diagnosed with the condition in Australia. The risk increases with ‘increasing texturing of the implant’; smooth surfaced implants have not been associated with BIA-ALCL.
BIA-ALCL can occur after either reconstruction or augmentation surgery, with 95% of cases occurring between 3-14 years after insertion of an implant.
Q: How BIA-ALCL diagnosed?
A: If you develop swelling of an implanted breast, your doctor will send you for an ultrasound scan to see if this is due to a fluid collection. If fluid is present, it will be removed and sent to a laboratory for analysis.
Most fluid collections are not due to BIA-ALCL; however if confirmed, your doctor may also order an MRI or CT scan to assess the extent of local growth or distant spread of the cancer (a PET scan may also be used to assess spread).
A mammogram will check for breast cancer, but is not useful for detecting BIA-ALCL.
Q: What is the treatment and prognosis for BIA-ALCL?
A: In about 80% of cases the disease is detected in the early stage, with cancer cells found only in the fluid surrounding the implant; most of these cases are cured by removal of the implant and surrounding capsule. Over the last 10 years, 4 Australian women have died from breast implant-associated lymphoma.
Usually both implants are removed, even if BIA-ALCL has only occurred in one breast – because there is a small, but real, risk it can develop in the opposite breast.
Q: How do I spot the symptoms?
A: The most common symptom is swelling caused by fluid build-up around the implant; but in some cases it may appear as a lump in the breast or armpit.
However as this is a rare disease, changes in your breast are unlikely to be breast implant associated cancer; for example, swelling immediately after implant surgery is normal. Nevertheless you should raise all concerns with your surgeon.
As a general rule, get to know the ‘normal look and feel’ of your breasts; self-examine your breasts regularly, such as in the bath or shower, and include your armpits and up to your collarbone.
It is also important to understand that generally breast implants are not ‘lifetime devices’ regardless of BIA-ALCL; typically they are removed after 10-15 years.
The longer you have the implant, the more likely it will need to be removed. Common reasons for removal are contracture (hard or painful implants) or movement of the implant.
BIA-ALCL: TGA ‘info for health professionals’
Australia’s Therapeutic Goods Administration (TGA) has also published a ‘BIA-ALCL: Information for Health Professionals’ summary.
The TGA emphasised: ‘As BIA- ALCL is rare, various aspects of this disease are not fully characterised. A more complete picture is expected over coming years. Health professionals should keep informed of the latest evidence.’
The TGA summary includes these Questions and Answers.
Q: What is BIA-ALCL?
A: BIA-ALCL is a rare form of non-Hodgkin lymphoma, classified by the World Health Organisation (WHO) in 2016 as a distinct clinical entity, separate from other categories of ALCL.
Its unique characteristics include: being purely T-cell; having no anaplastic lymphoma kinase gene translocation (ALK); being CD30 receptor protein positive on immunohistochemistry (CD30+); being in close anatomical association with a breast implant.
The aetiology of BIA-ALCL appears complex and multi-factorial; the complete set of causal factors is unknown. Breast implants are likely to be necessary, but not solely- sufficient to cause BIA-ALCL. Inter- related factors have been proposed that include: textured implants (with a higher risk for high surface area textures); bacterial contamination at the time of surgery to cause inflammation; patient genetic predisposition; time for the process to develop.
Most cases occur between 3-14 years after insertion of the implant (median 8 years, range 1-37 years). The risk appears between 1-in- 2,500 and 1-in-25,000 patients with implants, based on confirmed cases where only one brand of implant had been used. The risk increases with increasing texturing of the implant.
To date in Australia there have been no cases in patients who have a history of implantation with only smooth implants; all Australian cases have occurred with textured or polyurethane implants.
Q: Discussion of BIA-ALCL risk with patients?
A: The risk of BIA-ALCL must be discussed with the patient as part of obtaining ‘informed consent’, including the benefits and risks of different types of implants for their clinical circumstance. They should also be provided with educational material to read and consider at leisure.
After implantation, you should provide patients with written details about the name and type of implant and the procedure performed, including the breast implant manufacturer’s labelling, patient information leaflet and patient- specific implant card.
Women with implants should be made aware of the common presenting symptoms including asymmetry, pain, delayed effusion or seroma, or less commonly a mass or lymphadenopathy.
They should be reminded that generally breast implants are not lifetime devices, regardless of BIA- ALCL; typically they are removed after 10-15 years. Common reasons for removal are contracture, rippling, movement or rupture of the implant.
Q: Steps to reduce your patient’s risk?
A: Current data suggests the lower the surface area texture of the
implant, the lower the risk of ALCL. A current hypothesis, but not proven, is T-cell stimulation due to a chronic bacterial biofilm infection increases the risk of ALCL developing. Therefore standard-of- care preparations, such as antibiotic prophylaxis, pocket irrigation, sterility and skin preparation should be maintained when placing an implant.
A group of Australian breast implant researchers, led by Professor Anand Deva, has made the following recommendations:
- Use intravenous antibiotic prophylaxis at the time of anaesthetic induction.
- Avoid peri-areolar incisions; these have been shown in both laboratory and clinical studies to lead to a higher rate of contracture as the pocket dissection is contaminated directly by bacteria within the breast tissue.
- Use nipple shields to prevent spillage of bacteria into the pocket.
- Perform careful atraumatic dissection to minimise de-vascularised tissue.
- Perform careful haemostasis.
- Avoid dissection into the breast parenchyma. The use of a dual-plane subfascial pocket has
- anatomic advantages.
- Perform pocket irrigation (refer to hospital or health department guidelines).
- Use an introduction sleeve; we recommend use of a cut-off surgical glove to minimise skin contact.
- Use new instruments and drapes, and change surgical gloves prior to handling the implant.
- Minimise the time of implant opening.
- Minimise repositioning and replacement of the implant.
- Use a layered closure.
- Avoid using a drainage tube, which can be a potential site of entry for bacteria.
- Use antibiotic prophylaxis to cover subsequent procedures that breach skin or mucosa.
Q: Investigation of suspected BIA-ALCL cases?
A: The main method of investigation is ultrasound evaluation to: confirm the presence and extent of an effusion; determine if there is presence of a mass; and evaluate regional lymph node basins for lymphadenopathy.
Fine needle aspiration of an effusion is performed and the aspirate (tissue) is sent for cytology and flow cytometry molecular studies for confirmation of BIA-ALCL.
There does not appear to be a role for mammography in detection or investigation of BIA-ALCL.
Research has shown the disease can be categorised into stages, with:
- 63% of reported Australian cases having cancerous cells limited to the fluid (effusion/seroma) surrounding the implant and not present in the tissue surrounding the implant; and
- a further 23% having cancerous cells limited to the seroma and the tissue capsule that is removed upon explant of the implants.
Most diagnosed cases are adequately treated with complete capsulectomy and implant removal; however aggressive variants have been reported (4 deaths in Australia have been confirmed to the TGA).
