More cases of a rare T-cell lymphoma associated with breast implants have been reported, says the US Food and Drug Administration (FDA).
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) can develop in the capsule around a silicone gel- or saline-filled implant used in breast reconstruction after mastectomy or in cosmetic breast augmentation. The average lag time between surgery and diagnosis is 9.2 years.
"We understand that the information presented shows an increase of 246 new MDRs since last year," the agency adds.
An in-depth analysis suggests that this corresponds to 457 unique cases of BIA-ALCL, including nine patient deaths.
The FDA explains that the number of unique cases is lower than the total number of reports because the FDA's medical device reporting system allows patients, providers, and manufacturers to each file their own reports even if it is about the same case, which can lead to duplicate reports.
The agency also issued a letter to healthcare providers, saying: "We want to ensure that all providers who treat patients with breast implants have information regarding identification, diagnosis, and treatment. Patients are more likely to seek routine care from primary care physicians, gynecologists, and others besides their treating plastic surgeon."
"Doctors and patients need to be aware of this and patients need to know what kind of implant they have," said Alan Matarasso, MD, president of the American Society of Plastic Surgeons (ASPS), and clinical professor of surgery at Hofstra University/Northwell School of Medicine in Hempstead, New York.
"In the vast majority of patients with confined disease, total capsulectomy with removal of the implant and any lumps or masses is curative," he told Medscape Medical News in an interview.
Concern Over Textured Implants in Europe
In recent months, concern about the risk for BIA-ALCL in women with textured implants has escalated in Europe, where 85% of the implants used in breast surgery are textured. (Notably, 85% of implants used in breast surgery in the US are smooth, said Matarasso.)
Professional and regulatory bodies in the UK and France issued warnings in August, recommending the use of smooth implants.
Then in December, the National Agency for the Safety of Medicines & Health Products (ANSM) in France went a step further, recommending that all textured implants across Europe be recalled when product certification expired. On December 19, Allergan, one of the world’s largest breast implant manufacturers, announced it was suspending European sales of its Microcell and Biocell textured breast implants.
Matarasso told Medscape Medical News that "a moratorium" has been declared on the use of textured breast implants in France, with surgeons performing prophylactic implant removal in concerned patients. "Fortunately, this has been a very rare situation," he said.
In its latest figures (as of January 25), the ASPS has recognized 265 cases of BIA-ALCL in the US and 673 unique cases in more than 30 countries worldwide.
Based upon current confirmed cases and textured implant sales data over the past two decades, the ASPS estimates that the current lifetime risk of BIA-ALCL in US women is about 1 in 30,000. "This is an extraordinarily rare illness," said Matarasso.
When approached for comment, David Euhus, MD, chief of breast surgery in the Division of Surgical Oncology, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, told Medscape Medical News there have been no reports of BIA-ALCL at that institution, where none of the surgeons use textured implants.
Autologous breast reconstruction is always discussed as an option to breast implants "but not because of concerns surrounding BIA-ALCL," said Euhus.
He estimated that 25% of patients are generally aware of BIA-ALCL, and that "late seromas or implant capsule-associated masses prompt careful imaging and a needle biopsy."
Constance M. Chen, MD, clinical assistant professor of plastic surgery at Weill Cornell Medical College in New York City, and at Tulane University School of Medicine in New Orleans, Louisiana, also said she does not have any patients with BIA-ALCL. However, she said she has responded to patient concerns by testing all those with implant seromas and implant capsules for CD30 antigen, a marker for ALCL.
"That said, the focus of my practice is natural tissue breast reconstruction and breast implant removal with complete en bloc capsulectomy, which is the treatment for ALCL," she told Medscape Medical News.
In a statement, Chen noted that all breast implants remain approved for breast reconstruction or cosmetic enhancement in the US. However, she predicted that this could change as more data on BIA-ALCL becomes available. The fact that many plastic surgeons have stopped using textured breast implants but continue to use smooth breast implants creates "a false sense of security," said Chen.
For women considering breast reconstruction after mastectomy, autologous reconstruction is a potential alternative, Chen pointed out. This could also be an option, once the implants are removed, for women who have undergone cosmetic breast augmentation. Accepting a smaller breast size would be another option, said Chen.
The ASPS estimates that a total of 550,000 breast implants are used each year in the US and that of these, 70,000 are textured. This trend has remained stable over the past 6 years.
Almost 56% of BIA-ALCL cases have been reported following cosmetic breast enhancement, Matarasso said, with 44% of cases reported in breast cancer survivors who have received implants as part of breast reconstruction.
Matarasso emphasized the importance of differentiating BIA-ALCL from primary lymphoma of the breast. The latter is predominantly a B-cell lymphoma with an incidence of about 1 in 4 million, he said.
As previously reported by Medscape Medical News, BIA-ALCL is always CD30 positive and anaplastic lymphoma kinase (ALK) negative. The disease spectrum ranges from indolent CD30-positive fluid collections within the capsule, to capsular tumors, to lymph node involvement and in rare cases, distant metastases.
In 2016, the National Comprehensive Cancer Network (NCCN) issued standardized guidelines for the diagnosis and treatment of BIA-ALCL.
Regular routine monitoring of the breast implant is mandatory with prompt investigation of any breast changes, particularly late-onset persistent seroma, says the ASPS on its website. When seroma is delayed for more than a year, fluid should be aspirated and sent for CD30 immunohistochemistry, cytology, and flow cytometry, "H&E [hematoxylin and eosin] staining can frequently miss the diagnosis," the ASPS says.
In the 35% of women with BIA-ALCL confined to the capsule, or in the 40% with a resectable mass, total capsulectomy and implant removal is often curative. However, in the 14% of patients with lymph node metastasis or the 1% with organ metastasis, chemotherapy may be required, said Matarasso. Radiation therapy should be reserved for patients with local unresectable disease involving the chest wall and mediastinum.
There is strong worldwide data on BIA-ALCL, said Matarasso, adding that "it is probably a combination of four risk factors."
Since BIA-ALCL has only been reported in textured implants so far, the type of device is considered a risk factor, he continued. Studies looking at the impact of different types of implant texturing indicate that some have greater or lesser effects on the development of BIA-ALCL.
Other risk factors include the length of time after implantation, and the amount of chronic inflammation caused by the implant. Genetics may also play a role, said Matarasso, noting that certain geographic locations have demonstrated variable risks for textured implants.
In December 2016, for instance, Australia and New Zealand reported a risk of 1 in 1000 to 1 in 10,000 women. Researchers in the Netherlands recently reported a risk of 1 in 6900 women, and Health Canada has estimated a risk of 1 in 24,000 women based on five reported cases.
"These discrepancies may represent variable reporting or may represent geographic and genetic predisposition, which is under investigation," the ASPS points out.
In the meantime, all confirmed cases of BIA-ALCL should be reported to the FDA's Manufacturer and User Facility Device Experience (MAUDE) database, to the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma Etiology and Epidemiology (PROFILE) registry at ASPS, and to the implant manufacturer. The FDA and the ASPS/Plastic Surgery Foundation (PSF) are collaborating to prospectively track BIA-ALCL in the US, said Matarasso.
The issue of BIA-ALCL will also be discussed at next month's meeting of the General and Plastic Surgery Devices Panel, to be held March 25-26 at the FDA's headquarters in Silver Spring, Maryland.
Matarasso and Euhus have disclosed no relevant financial relationships. Chen reported relationships with AxoGen and KCI.
Medscape Medical News © 2019
Cite this: Breast Implant Link to Rare T-Cell Lymphoma an Ongoing Concern - Medscape - Feb 06, 2019.