More Info on Risks of Breast Implants Needed, Says FDA Panel

Kerry Dooley Young

March 27, 2019

During a 2-day meeting on breast implants at the US Food and Drug Administration (FDA), a panel of federal medical advisers offered wide-ranging — and at times conflicting — suggestions for addressing known, suspected, and claimed risks from these products.

One of the risks is breast implant–associated anaplastic large cell lymphoma (BIA-ALCL), which is an ongoing concern, the FDA noted recently.

Although some panel members called for a ban on certain products, others emphasized the lack of data, and a range of different opinions was expressed during the free-flowing panel discussions.

At this meeting, the FDA did not ask the panel to vote on a specific set of recommendations, as it usually does during meetings of its advisory panels. Instead, the agency tasked this panel to broadly consider several topics, including improving the informed consent process and investigating the issue of BIA-ALCL.

At least one clear message emerged: physicians must help women better understand risks and shortcomings of breast implants, including the risk of developing the rare lymphoma.

Patients need to have more "realistic expectations" about these devices, said Frank R. Lewis Jr, MD, the chairman of the FDA's General and Plastic Surgery Devices Advisory Committee, in summarizing key points from of the March 25–26 meeting.

"Breast implants should not be regarded as a permanent fix that you can forget about and never expect problems," said Lewis, who earlier served as executive director (2002–2017) of the American Board of Surgery.

Patients often are unaware of the information that they need in order to make a sound decision about receiving breast implants, many panelists said. They may be confused by the dense documents that are written to please corporate lawyers, and they may not be savvy enough to press for simpler explanations of potential risks.

Panelist Natalie Compagni Portis, PsyD, suggested adopting tactics similar to those used to pitch costly medicines to Americans and to make the public aware of the dangers of smoking.

"I'm not a big fan of direct-to-consumer advertising, but what if there were ads about these things [breast implants] on TV?" she asked — maybe something like a public service advertisement for breast implants, she suggested. "What if industry were required to do it or FDA were required to do it?" she asked.

Members of the public attending the FDA hearing loudly applauded this idea from Portis, who served as the panel's patient representative.

Lymphoma Associated With Textured Implants

BIA-ALCL has been linked to textured implants, although there are case reports implicating smooth implants, the FDA said in the briefing materials for the meeting.

Textured implants are used more commonly in Europe, where they represent about 85% of the market, the American Society of Plastic Surgeons (ASPS) recently told Medscape Medical News. In the United States, smooth implants dominate.

Professional and regulatory bodies in the United Kingdom and France raised alarms last year about BIA-ALCL. One specific product, Allergan's Biocell textured implants, has been recalled in 33 European countries, as well as Israel and Brazil, the FDA said in a briefing for the March 25–26 meeting. Last month, a panel convened by the French National Agency for Medicines and Health Products Safety called for a ban on the Biocell product.

At this meeting, the FDA did not ask its advisory committee to directly address whether to seek a ban on textured implants.

Nevertheless, during the course of the meeting, two panelists separately suggested blocking these products from the US market.

Call to Ban Biocell Implants

During Tuesday's closing session, Pierre M. Chevray, MD, PhD, a plastic surgeon from Houston Methodist Hospital, Texas, noted that other nations already have acted to prevent people from receiving Allergan's Biocell implants, which are distinctive for a feature known as salt-loss texturing.

"I think that [a ban] should be considered by the FDA in this country," Chevray said. "That one particular type of texturing has been identified as being just so much higher at risk of being associated with lymphoma that it's striking actually."

In its presentation to the FDA, an Allergan rival claimed that its textured implants appear much less likely to cause BIA-ALCL.

Johnson & Johnson's Mentor implant unit said the overall incidence of BIA-ALCL among patients with Allergan's Biocell implants was 1.87 per 1 million person-years. In contrast, the overall incidence rate of BIA-ALCL among patients with Mentor's Siltex textured implants was 0.33 per 1 million person-years. Mentor said its imprinted textured implants were associated with a significantly lower incidence rate (P < .001).

When asked by Medscape Medical News to respond to this point, Allergan replied with a statement that addressed its efforts to mitigate the introduction of bacteria in the surgical environment and subsequent biofilm formation on implants. It has been proposed that bacteria and biofilm on breast implants are a cause of BIA-ALCL, perhaps in relation to a sustained T-cell response (Plast Reconstr Surg. 2017 Sep;140:427-431).

Enhanced aseptic steps were put in place for use during implant procedures in response to this concern, Allergan said.

"When these and other steps were taken, researchers reported no cases of BIA-ALCL in 42,000 patients with Biocell implants," Allergan said in its statement to Medscape Medical News.

"The safety profile of Allergan's breast implants is supported by extensive preclinical device testing, more than a decade of US and European clinical use as well as a large number of peer-reviewed and published studies," the company said in its statement.

Public Call for Ban

At the meeting, there was clear interest from the public in having US regulators block use of textured implants.

Members of the public strongly applauded Chevray's suggestion on Tuesday for a ban on Biocell implants, as they did regarding a call on Monday for blocking access to textured implants from panelist Rachel S. Brummert, president of the Quinolone Vigilance Foundation. Brummert, who served as the FDA panel's consumer representative, became involved in patient safety issues after suffering tendon ruptures after using the quinolone antibiotic levofloxacin (multiple brands).

Brummert highlighted cases of BIA-ACLC that had occurred in women who had undergone breast implantation after mastectomy as part of their treatment for breast cancer.

"A lot of these women who get the implants, they had cancer already, and then they get the textured implants and they are getting cancer again," Brummert said at the FDA meeting. "That's so much of a risk that I think they need to be taken off the market."

Arguing Against a Ban

However, some of the FDA panelists disagreed with the proposal for a ban on textured implants.

Mary H. McGrath, MD, MPH, a plastic surgeon from the University of California, San Francisco, suggested the textured implants may produce better results and thus spare patients from repeat procedures. Other implants might not stay in place without the use of surgical mesh.

At the meeting, the FDA also sought the panelists' feedback on approaches to gain a greater understanding of the risk and benefits of the mesh — acellular dermal matrix (ADM) — that is used with breast implants.

In the briefing materials for the meeting, the FDA said it is wrestling with a "mismatch between widespread clinical use of surgical mesh in breast reconstruction and the lack of data or FDA approval justifying its use."

"That's what we are weighing here. If we felt confident that wrapping the implants with ADM — with the mesh — was safe and as effective as the texturing, then I would absolutely agree with you [to call for a ban]," McGrath told Brummert. "But I don't know that, and there's a real downside to this, too. Completely losing texturing would be very problematic."

Unanswered Questions

It's not yet firmly established that the texturing on the surface of implants is the culprit in BIA-ALCL, said FDA panelist Stephen Li, PhD, a biomaterials expert.

He conceded that the data gathered so far suggest that a "highly textured" implant appears to be associated with a greater incidence of BIA-ALCL.

But Li said he was "very uncomfortable" about attributing all of the increased incidence to the texturing of the Allergan product.

"I'm not convinced what the mechanism is," Li said. He noted that other bacteria can grow on other textured implants. "It just doesn't seem to me that it's just texture."

He said he feared there was a drive to oversimplify the approach and hone in on the Allergan product.

"We could be like Europe and say, 'Listen, there's enough worry here. Let's just take this one off the market,' " Li said, but he pointed out that "they didn't take the others that had similar textures off the market, they just took that one."

Citing data from the ASPS, the FDA noted that there have been 673 worldwide cases of BIA-ALCL as of January 16, 2019, with 16 disease-related deaths. In a February update, the ASPS said it was aware of 688 cases worldwide, with 17 disease-related deaths in 30 countries.

Implants Used for 50 to 60 Years

Although the rare cancer was the marquee issue of the meeting, the cause of BIA-ALCL was far from being the FDA's only serious question about breast implants. The agency mentioned the possible use of artificial intelligence and mobile apps to collect and analyze data on what has been described as "breast implant illness," which covers a variety of common conditions, such as fatigue, rashes, and memory loss.

"Breast implants were invented in the early 60s and have been available to patients for close to 50 to 60 years, and we're still arguing about their safety," commented Sybil Niden Goldrich, a long-time activist regarding the risks of these devices.

Last year, 313,735 breast augmentation procedures were performed in the United States, said the ASPS. The group said its members performed 101,657 breast reconstruction procedures.

The nonprofit National Center for Health Research also cited data: "More than 300,000 women and teenagers underwent breast implant augmentation surgeries in 2017. In addition, approximately 106,000 women underwent breast implant surgery for reconstruction after mastectomy. The popularity of breast implants has risen dramatically in the last 20 years and is now more than three times the 1997 rate of 101,176."

In 1992, the FDA restricted use of silicone breast implants because of concerns about leakage. It then approved them in 2006, but asked companies to conduct large, long-term safety studies.

Earlier this month, the FDA issued warning letters to two manufacturers, Johnson & Johnson's Mentor Worldwide unit, and Sientra, Inc, because of their failure to fulfill their breast implant post-approval study requirements.

At the meeting, panel members expressed frustration at the limits of the agency's knowledge about the safety of breast implants.

"Today's medicine is practiced as evidence-based medicine," said Colleen M. Gallagher, PhD, who is executive director for integrated ethics at MD Anderson Cancer Center in Houston, Texas.

"The number of times that I sat here in these last 2 days listening to 'we don't have the data, we don't have the information, we don't know the answer'.... That's problematic," she commented.

BIA-ALCL Is a "Man-made Cancer"

During the meeting, there were four periods for public comment. During these sessions, several women told the panel about how they developed BIA-ALCL.

Among them was activist Raylene Hollrah, from Missouri.

Hollrah was diagnosed with breast cancer at age 33. After undergoing a bilateral mastectomy, she opted for implants. She told the FDA panel that she consulted three plastic surgeons, who told her that implants would be a safe choice. She said she was among the patients meant to be included in a long-term implant study.

"Ironically, I was dropped from that study at the same time I was diagnosed with my second cancer, with no reason or notification why," Hollrah said, referring to BIA-ALCL.

"Yes, a man-made cancer from my breast implants," Hollrah added. "I was never warned. I was never notified of the risk, and my life was forever changed again from another cancer diagnosis."

She said that to date, her healthcare costs related to treatment of BIA-ALCL have amounted to more than $288,000, not including time lost from work. She urged the FDA to take steps to make women aware of the risks of implants.

"We need a mandated patient informed consent, we need a mandated black box warning, we need a mandated patient checklist," Hollrah told the panel.

In its questions to the panel, the FDA proposed ideas such as a checklist or efforts to help patients better understand the risks of breast implants.

No Immediate Plans

The FDA has not disclosed any immediate plans regarding breast implants. It offered only a vague statement at the end of the meeting.

"The insightful feedback and deliberations will help inform the FDA's own thinking as we consider ways to promote informed benefit and risk discussions between patients and their providers, and what, if any, additional steps should be taken to improve breast implants safety," agency spokeswoman Stephanie Caccomo said in an email to Medscape Medical News.

In part, the FDA's decision to hold the meeting drew attention to its message about the risks and limits of implants, inasmuch as the meeting was widely covered by a range of media, including coverage on prime time television.

"Breast implants are not lifetime devices and the longer a patient has the implants, the more likely they are to experience local complications and adverse outcomes requiring breast implant removal," the FDA staff wrote in the briefing for the meeting.

Many patients are not informed about these shortcomings of implants, argued another member of the public, Meredith Garr Kilmer of Raleigh, North Carolina. She was among the women who told the FDA panel about breast implant illness. Kilmer told the panel that patients must be clearly presented with information about the risks of transplants so that they can make informed decisions.

"I never received a booklet or was told they would need to be replaced," Kilmer said. "I was told they were safe, FDA approved, and would outlive me in my grave."

Chevray has received compensation for expenses for food and beverages from Allergan and other companies. McGrath has received compensation for expenses for food and beverages from Mentor.

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