ALCL more common than previously thought

New research has found a link between bacteria on breast implants and anaplastic large cell carcinoma, a rare form of immune system cell cancer.

New research has found contaminated breast implants may increase the chance of women developing a rare type of cancer.

Recently published in Plastic & Reconstructive Surgery Journal, the Australian-led research looked at tissue samples from 22 women who developed a rare form of non-Hodgkin lymphoma called anaplastic large cell carcinoma (ACLC) after undergoing breast enhancement procedures.

It was found that the women developed ALCL within eight years of having the surgery. Led by Associate Professor Anand Deva from Macquarie University’s Health Sciences Centre, this is the first time that implants contaminated with bacteria have been linked to this type of lymphoma.

Professor Deva’s previous research has found bacteria that live in clumps attached to breast implants are a major cause of capsular contracture.

It has been found that bacteria gain access to the implant’s surface, most commonly at the time the implant is inserted. Once attached to the implant, they secrete a thick sticky ‘glue’ and become a firmly adherent bacterial biofilm.

“Once you have a contaminated prosthetic in the body, the body can’t get rid of it,” Dr Deva told the Australian Broadcasting Commission (ABC). “This chronic irritation goes on and on, and over a period of time, it stimulates the immune system where some of these cells can potentially transform into cancer.”

Researchers also found that implants with a textured surface were 70 times more likely to be associated with bacteria than smooth surfaced implants. “We now know macro-textured implants, which have a higher surface area, carry a significantly higher risk of BIA-ALCL,” Dr Deva said.

“If breast implant surgery is performed without proper infection controls, bacteria can enter the body and slowly cause scar tissue to harden around the implants.”

Over several years, the infection puts stress on the patient’s lymphatic system and in some cases triggers ALCL.

It was previously estimated that the risk for ALCL stood between one in three million to one in 50,000, however the TGA now estimates that it ranges between one in 1,000 and one in 10,000.

What is breast implant-associated ALCL?

This is a rare form of non-Hodgkin lymphoma. In 2016, the WHO classified breast implant-associated ALCL (BIA-ALCL) as a distinct clinical entity, separate from other categories of ALCL.

Unique characteristics include:

• being purely T-cell
• having no anaplastic lymphoma kinase gene translocation (ALK-)
• being CD30 receptor protein positive on immunohistochemistry
• being in close anatomical association with a breast implant.

How can the risk be reduced?

Based on advice from an expert advisory committee, the TGA says the currently available data suggest that the risk might be reduced by using smooth implants.

In addition, a hypothesis currently in favour, but not proven, is that T-cell stimulation due to a chronic bacterial biofilm infection increases the risk of ALCL developing. Therefore, standard-of-care precautions, such as antibiotic prophylaxis, antibiotic irrigation, sterility and skin preparation should be maintained when placing an implant. It is also hypothesised that such precautions would have the additional benefit of reducing the risk of contracture.

A group of Australian breast implant researchers have made the following recommendations:
1. Use intravenous antibiotic prophylaxis at the time of anaesthetic induction.
2. Avoid periareolar 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.
3. Use nipple shields to prevent spillage of bacteria into the pocket.
4. Perform careful atraumatic dissection to minimise devascularised tissue.
5. Perform careful haemostasis.
6. Avoid dissection into the breast parenchyma. The use of a dual-plane, subfascial pocket has anatomic advantages.
7. Perform pocket irrigation with triple antibiotic solution or betadine.
8. Use an introduction sleeve. Use of a cut-off surgical glove to minimise skin contact is recommended.
9. Use new instruments and drapes, and change surgical gloves prior to handling the implant.
10. Minimise the time of implant opening.
11. Minimise repositioning and replacement of the implant.
12. Use a layered closure.
13. Avoid using a drainage tube, which can be a potential site of entry for bacteria.
14. Use antibiotic prophylaxis to cover subsequent procedures that breach skin or mucosa.

While it is essential to be aware of the latest evidence and developments, it is important to understand that the risk is still very small. In Australia, 46 women have been diagnosed with ALCL in the past 10 years. ‘Normal’ breast cancer is 40,000 times more common.

Dr Deva urges Australian doctors not to panic, stressing that only a small percentage of women have gone on to develop cancer: “There’s probably about 300 cases worldwide.”

Instead, women should monitor their breasts for any changes and consult their surgeon if they have concerns. Signs may include a palpable mass in the breast or axilla, generalised breast pain, or breast firmness.

The TGA does not recommend preventative breast implant removal in patients without symptoms or other abnormality. Based on external expert clinical advice received by the TGA, regular screening is also not recommended at this time.

“It’s important to emphasise that the risk still remains very low, so unless there are associated symptoms such as a sudden swelling of the breast or a lump, women do not need to have implants removed. However, we recommend women get their implants checked regularly,” said Australian Society of Plastic Surgeons (ASPS) president, Dr James Savundra.

“The vast majority of women with swelling of the breast do not have BIA-ALCL but it should be investigated via an ultrasound scan with the fluid around the implant analysed,” said Dr Savundra.

ASPS is developing a national register of member surgeons who are willing to see concerned women with symptoms and assess their implants for no out-of-pocket expense consultation.

ASPS and ASAPS are also pushing for the creation of a mandated breast device registry that would capture all women with breast implants, allowing researchers to track problems associated with the implants and act as an early warning system when issues arise.

The new research findings are significant and reveal that breast implant cancer may be more common than previously thought. They offer a valuable insight for surgeons, breast imagers and oncologists into the diagnosis, treatment and prevention of this rare but deadly cancer. With further research, there will be a focus on revolutionary anti-bacterial technologies that will prevent implant infection.

Because breast implant-associated ALCL is rare, various aspects of this disease are not fully characterised. With further studies, a more complete picture is expected over coming years. However, it becomes essential for health professionals to keep themselves apprised of the latest evidence and know how to reduce risks.

What to tell your patients

The possibility of breast implant-associated ALCL should be included in informed consent. The disease is rare. A one-number estimate of the risk is not possible with the currently available data. Current expert opinion is that the risk is between 1 in 1000 and 1 in 10,000 women with implants. Most cases occur between 3 and 14 years after insertion of the implant (median: 8 years; range: 1-37 years).

Based on the currently available data, BIA-ALCL does not seem to occur when only smooth implants are used. All Australian cases to date have occurred in women with textured or polyurethane implants.

Women with implants should be made aware of the common presenting symptoms: delayed effusion/seroma or, less commonly, a mass or lymphadenopathy.

Based on the current epidemiological evidence, the expert panel advised the TGA that breast implants were likely to be a necessary, but not sufficient, cause of breast implant-associated ALCL. The expert panel’s reasoning included:

• the ALCL cells occur in close proximity to the implant
• breast implant-associated ALCL is a distinct clinical entity, separate from other categories of ALCL2
• ALCL, with the distinct features of BIA-ALCL (eg, ALK-negative, CD30-positive, typical clinical course), has not been reported in the absence of an implant.

The complete set of causal factors is unknown. To date, no patient-specific susceptibility factors, which might help predict risk, have been identified.

STATEMENT FROM THE TGA

Expert advisory panel advice on association with anaplastic large cell lymphoma

20 December 2016

As part of the TGA’s ongoing monitoring of the association between breast implants and anaplastic large cell lymphoma (ALCL), consumers and health professionals are advised that an expert advisory panel was convened to discuss the issue on 16 November 2016 and has been providing ongoing advice.

The expert advisory panel included representation from plastic surgeons, cosmetic surgeons, breast-cancer surgeons, cancer epidemiologists, data analysts and public-health practitioners. The panel’s advice is outlined in the ‘Information for consumers’ and ‘Information for health professionals’ sections on the TGA website (see link below).

Breast implant-associated ALCL is a rare type of lymphoma that develops near breast implants. The TGA published safety communications regarding this issue on 27 January 2011 and 27 September 2016.

Since the last safety communication, the TGA has been provided with additional data and is advising that 46 cases of breast implant-associated ALCL have now been confirmed in Australia, including three that resulted in death. These cases have all occurred since 2007. Most cases of breast implant-associated ALCL are cured by removal of the implant and the capsule surrounding the implant, however a small number are more aggressive.

The TGA is also aware of a small number of unconfirmed cases. These are being investigated.

Consumers and health professionals are asked to report any suspected cases to the TGA.

Future TGA actions

• The TGA will work with research groups to obtain better estimates of the risk of breast implant-associated ALCL.

• The TGA will work with manufacturers, Australian experts on breast implant-associated ALCL, and Australian experts on breast augmentation and reconstructive surgery to evaluate the benefit-risk balance of the various types of breast implants.

• The TGA will continue to liaise with its major overseas regulatory partners and collaborate in international working groups.

… For women who already have implants, the current consensus of expert opinion is that screening or prophylactic removal in asymptomatic patients is not recommended.

Because breast implant-associated 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 themselves apprised of the latest evidence.

See www.tga.gov.au/alert/breast-implants for more information, including Q&As for both patients and practitioners, references and how to report problems.