The US Food and Drug Administration (FDA) announced on July 24, 2019, that at the agency’s request, Allergan had issued a worldwide recall of certain models of its BIOCELL textured saline- and silicon-filled breast implants because of the risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The recall was a reversal of the FDA’s previous position that the implants should be kept on the market – and came on the heels of headlines about the agency’s failure to disclose thousands of breast implant-associated injuries and complications.1
As of July 24, 2019, the FDA had received reports of 573 pathology-confirmed cases of BIA-ALCL, 90.5% of them involving Allergan products, 7% related to Mentor breast implants, and 1% that could be linked to Sientra implants. Latency periods (lag times) between implantation and BIA-ALCL diagnosis have varied widely, from approximately 2 years to 27 years, with a mean lag time of 9.75 years.
Cases of BIA-ALCL have been suspected as far back as 1997, according to the FDA. But some researchers had raised the alarm much earlier.
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“We first reported our own concerns about breast implant-associated lymphoma in 2004,” recalled Leslie L. Popplewell, MD, a hematologist/oncologist at the City of Hope Comprehensive Cancer Center’s Toni Stephenson Lymphoma Center in Duarte, California.2 “They were all ALCL cases.”
It is unclear why textured breast implants might sometimes lead to ALCL. Local immune inflammatory responses and autoimmune responses might be factors — although to date, autoimmune responses have not been tied directly to BIA-ACL, cautioned Mark W. Clemens, MD, FACS, a plastic surgeon at the University of Texas MD Anderson Cancer Center in Houston.
Soft tissue implants invariably develop fluid capsules around the implant, noted study coauthor Daniel J. Gould, MD, PhD, division of plastic surgery, the University of Southern California, Los Angeles. Bacterial biofilms might have more opportunity to grow on their larger surface areas than those of smooth implants, or textured surfaces might irritate and inflame surrounding tissue. But neither the inflammation nor the bacterial hypothesis — the 2 are not necessarily mutually exclusive — has yet been confirmed, Dr Popplewell said. Implants can shed particles that appear to trigger peri-implant inflammation but their role in ALCL, if any, is far from clear.3
Preclinical studies have shown that in vitro, surface texture can strongly influence cellular differentiation, Dr Gould noted.
“We know for cells placed on hard versus soft surfaces, or surfaces with a lot of room versus little, these can change the differentiation of cells,” he said. “We know that physical interactions and environments change cellular differentiation.”
“Some kind of chronic stimulatory inflammation that is created by textured implants is involved,” Dr Clemens said. “Some research has determined that a lot of these patients seem to be mounting allergic reactions but we don’t know exactly why. We have not determined an allergen that would lead to that. But they seem to be having inflammation consistent with an allergic reaction.”
“Breast implants are generally safe and do what they were intended to do,” Dr Clemens emphasized.
But, he added, when BIA-ALCL does occur, patient genetics appear frequently to be a factor.
“There seem to be genetic mutations that predispose patients, [and] that flip a normal inflammatory response into a T-cell lymphoma,” he explained. “Three mutations have been identified to date: JAK, STAT, and p53.”
The analysis by Dr Clemens and colleagues of the FDA’s long-term breast implant postapproval surveillance data identified an association between breast implants and melanoma (the implants in this situation were mostly cosmetic, rather than reconstructive).4 But that association between breast implants and skin cancer is unlikely to be causal, he said; patients who undergo non-reconstructive cosmetic breast enhancement also tend to have higher levels of sun exposure.
