AMP speaks with Prof Anand Deva about the current status of BIA-ALCL. In a rapidly moving area, here is what we know about the treatment, epidemiology, risk and pathogenesis of this emerging disease.

The first case of BIA-ALCL was reported in 1997 and, in the time since, its incidence has exponentially increased worldwide, culminating in the 2016 classification of BIA-ALCL as a unique disease entity by the World Health Organisation.

Research into the cause of this disease is a rapidly advancing area. Australian and New Zealand plastic surgeons are at the forefront of
this research, in collaboration with global partners and comprehensive patient databases, accruing epidemiologic data and literature
to help facilitate better surveillance and treatment.

Here we speak with Prof Anand Deva about the new understandings of BIA-ALCL.

Prof Anand Deva

Professor Anand Deva is a noted authority on BIA-ALCL and is the Director of Cosmetic and Plastic Surgery at the Faculty of Medicine and Health Sciences, Macquarie University and co-director of the Surgical Infection Research Group. He is considered a leading academic and has published widely on issues related to implant infection and wound healing.

What do we know about BIA-ALCL that we didn’t know three years ago?


We have a much better idea of epidemiology through global cooperation and tracking of cases, especially in Australia. We are zeroing in on the likely factors that cause it. We are also much more aware of 
it and, at least in Australia, we are picking up the majority of cases early, which translates into better survival and outcomes. In most cases, early diagnosis requires surgical treatment only for clearance of the tumour.

What is the new understanding of the medium- to long-term risks of breast implants? What are the triggering factors?

Clearly the risk of BIA-ALCL is highest for very rough implants. This has been supported by published risk data
 from Australia, New Zealand, US, UK and Canada. We have released a grading system [see table below] that measures surface area and surface roughness and using these parameters have classified implant surfaces into 4 grades.

The risk of BIA-ALCL for grade 3/4 implants (eg, biocell and polyurethane covered) is around 1 in 1,000 to 3,000. The risk drops significantly for grade 2 (around 1 in 15,000-30,000) and, to date, we do not have a confirmed case with exposure to grade 1 implants (smooth) alone. It is these data that regulators are using in part to suspend and/or cancel devices globally. Australia has just cancelled all remaining grade 3/4 devices.

We believe that long-term chronic inflammation drives transformation 
of T lymphocytes into lymphoma.
The likely causes of this inflammation include bacterial infection, particles and less likely allergic inflammation
or friction from rougher implants. The role of bacteria is supported by the increasing risk for surface grade – data shows that the rougher surfaces support the growth of more bacteria over time and we have just published data showing that bacterial antigens can talk to BIA-ALCL tumour cells and cause significant proliferation.

There is also increasing data evidence that the bacterial population living in and on our body (the microbiome) are a potent immune stimulator and changes to these bacteria can trigger both cancer and other disease.

We have put forward a unifying hypothesis that links four factors: bacteria living on textured implants interact with the immune system of genetically susceptible patients over time to cause BIA-ALCL.

How can these risks be mitigated? How do techniques employed in the operating theatre have a direct impact on outcomes?

To start with, the surgeon needs to provide informed educated consent
as to the risks of BIA-ALCL and breast implants in general. The FDA has just released informed educated consent checklists to ensure that patients are fully aware of the medium- to long-term risks of implants. I would encourage colleagues to become familiar with and start using them.

Secondly, the surgeon needs to be clear in his/her choice of implant type.

Thirdly, the use of bacterial mitigation in the operating theatre is critical and may reduce the risk of not just BIA- ALCL but also other adverse outcomes such as capsular contracture.
The use of textured devices and risk of BIA-ALCL needs to be clearly
of benefit in reducing the risk of reoperation and/or providing a better long-term stable outcome. We have published some early evidence suggesting that the certification/training of the practitioner and licensing of facilities where cosmetic augmentation are performed may significantly increase the risk of BIA-ALCL.

Finally, all patients with implants need lifelong surveillance. I have been advocating for many years that patients return for annual clinical review and periodic imaging with either MRI or ultrasound. I have done this for over 20 years – it is the best way as a surgeon to view your own outcomes, ensure that patients have continuity of care and, of course, learn how to become better at achieving good long-term results. Your own long- term results also make you more humble and more truthful about the real outcomes following breast implant surgery.

Breast implants are definitely not lifetime devices. Once again, the FDA has just released its recommendation for imaging of these devices. It would be great to see my colleagues now starting to offer surveillance programs to patients as part of their standard of care.

Where do you think the future of breast implant technology lies? Will there be increased consideration of the implant/host interaction process?

There is much work underway to improve the biological compatibility, tissue incorporation and immune tolerance of breast implants (and other medical devices).

The scrutiny of these devices prior to and after regulatory approval also needs to be overhauled. The history
of breast implants is littered with many devices that either had cursory testing and/or piggy backed on other devices to gain regulatory approval and then rushed to the marketplace for use in patients. The vetting and assessment of medium- to long-term safety of implantable devices needs to be better managed to ensure that devices approved for clinical use are safer.

How should surgeons be advising their patients?

Breast implants are not lifetime devices. They are not set and forget. This will not be the last operation on your breasts. You need to come back every year and #getchecked!

What do you see as the most important messages for both surgeons and the public at large?

Do not take the decision to have breast implant surgery lightly. #Beinformed and #Getchecked. AMP


The Unifying Hypothesis

A unifying hypothesis was presented in 2017 by Prof
 Deva in collaboration with the Joint BIA-ALCL Task Force, implicating a combination of high surface area textured implants, bacterial contamination, genetic susceptibility and time of exposure to explain its pathogenesis.

It has been hypothesised 
that the cancer is triggered by inflammation from bacteria residing within the textured surface of 
these implants, transforming the lymphocytes of some genetically prone patients over many years.
 A recent 2020 study submitted
 for peer review in Cancers, shows that bacteria are able to trigger activation and multiplication of these cancer cells in the laboratory, lending support that bacteria and their products play an important role in causation.

Unifying hypothesis
Textured breast implants, bacteria, genetics and time are the four factors thought to be at play.

Collaborative study to shed light on breast implant illness

Alongside the increased incidence and awareness of BIA-ALCL, breast implant illness (BII) has been thrust into the spotlight.

Breast Implant Illness is a
term used by women who have breast implants and who self- identify and describe a variety of symptoms, including fatigue, chest pain, hair loss, headaches, chills, photosensitivity, chronic pain, rash, body odour, anxiety, brain fog, sleep disturbance, depression, neurologic issues and hormonal issues that they feel are directly connected to their saline or silicone, textured or smooth breast implants.

It would appear the rise of patient advocacy and communication through social media has led to an increcrease in patients reporting BII symptoms. At the time of writing, one BII Facebook Group has more than 129,000 members.

While the relationship between breast implants and systemic disease has been reported since the 1960s, the debate continues today. Numerous studies of BII have neither supported nor refuted its existence and there is no o cial medical diagnosis.

BII, therefore, remains a challenging issue and is the subject of a new Australian collaborative study, led by Dr Mark Magnusson and Prof Anand Deva.

‘We have now over 500 women enrolled in our study (https://saferbreastimplants.org/breast-implant-removal/) and are now seeking to collaborate with colleagues around the world,’ says Prof Deva. ‘It will take a few years to tease out likely association and causative factors. I am grateful for the support of patients, colleagues and advocates. Together we
will ensure that women are kept informed and safe.’

The study suggests a two- pronged approach which is conditional on developing pathways for regular breast
implant surveillance. A new breast implant check clinic, commenced in Australia, is now scaling to two states and will provide an important low cost entry point for women with breast implant-related issues to be assessed both clinically and with imaging and/or pathology.

These clinics will serve to
capture patient, surgical, implant and outcome data. They will also serve to standardise work-up for patients with potential BII. These
will include wide ranging blood screening for autoimmune disease markers and also collect patient- reported outcome measure data with validated instruments such as the BREAST-Q, as pertaining to cosmetic surgery. These patients will need to be followed up closely and for a period of ≥2 years to
track their progress following explantation. The process of measuring the denominator, that is, number of implants deployed across a population over time, will allow assessment of the risk and scale of BII. International collaboration with national breast device registries
will also allow pooling these data
to generate overall risk for many breast-related complications.

The second part of this approach is to closely examine the implant, capsule, and peri-implant tissues to delineate the presence of pro-inflammatory substances and their subsequent e ect on
local tissues. The detection and characterisation of the microbiome on these implants and capsules will also be an important strategy to look for differences in measurable parameters between patients
 with BII and explantation for other indications, including capsular contracture, size change, intra-/ extracapsular rupture, and BIA-ALCL. These patients will also
 need genetic sequencing to look for patterns of gene mutations and HLA type that predispose to the development of autoimmune and other systemic disease. The analysis of various implant/patient and peri-implant parameters may also provide clues and patterns as to the natural history, pathogenesis, and outcome of patients with BII.

References

Keech JA Jr, Creech BJ. Anaplastic T-cell lymphoma in proximity to a saline- lled breast implant. Plast Reconstr Surg 1997;100(2):554-5.
Loch-Wilkinson A, Beath KJ, Knight RJW, et al. Breast Implant-Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand: High-Surface-Area Textured Implants Are Associated with Increased Risk. Plast Reconstr Surg. 2017, 140(4), 645-654.
Rastogi P, Riordan E, Moon D, Deva AK. Theories of Etiopathogenesis of Breast Implant-Associated Anaplastic Large
Cell Lymphoma. Plast Reconstr Surg.
2019 Mar;143(3S A Review of Breast Implant-Associated Anaplastic Large Cell Lymphoma):23S-29S.
Loch-Wilkinson A, Beath KJ, Magnusson MR, Cooter R, Shaw K, French J, Vickery K, Prince HM, Deva AK. Breast Implant-Associated Anaplastic Large Cell Lymphoma in Australia: A Longitudinal Study of Implant and Other Related Risk Factors. Aesthet Surg J. 2020 Jul 13;40(8):838-846.
Mempin M, Vickery K, Kadin M, Prince,
M, Hu H, Kouttab N, Adams, W, Deva AK. Gram-negative bacterial lipopolysaccharide (LPS) promotes tumor cell proliferation in breast implant associated anaplastic large-cell lymphoma. Cancers 2020, for peer review. Magnusson, MR, Cooter, RD, Rakhorst H, McGuire PA, Adams, WP, Deva, AK. Breast Implant Illness: A Way Forward, Plastic and Reconstructive Surgery: March 2019 – Volume 143 – Issue 3S – p 74S-81S.