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Lymphoma associated with breast implants occurred substantially more often than previously reported, according to a review of national cancer databases.

From 2008 through 2018, primary breast anaplastic large-cell lymphoma (ALCL) occurred at a rate of 8.1 per 100 million persons per year, which translated into a cumulative lifetime risk of 7.5/100 million at age 79. The rate increased over time, reaching 14.5/100 million for 2012 to 2018. That compared with an FDA estimate of 3/100 million for 2001 to 2007.

The higher rate of breast ALCL in the U.S. is consistent with reports from the Netherlands, and Australia and New Zealand. The rising case rate also coincided with increasing use of textured breast implants, which have been implicated in breast ALCL, reported Connor Kinslow, MD, of the Columbia University Vagelos College of Physicians and Surgeons in New York City, and co-authors in .

"Previous studies have underestimated the risk of this rare cancer after breast implantation," Kinslow told 乌鸦传媒. "The hope is that these data are going to contextualize previous studies [to improve] understanding that [the number of cases] have been underestimated and that they will continue to underestimate the rate of ALCL."

"Risk estimates have varied widely in previous studies and, accordingly, different governments across the world have had very different responses," he added. "In Australia they banned certain types of textured implants. In the U.S., they put a black box label on all implants. Some countries haven't taken any action. Getting more accurate risk estimates will help governments decide how they should be responding to this."

Though "certainly concerning," the findings came from a study period that ended in 2018, the year before the FDA and regulatory agencies in other countries issued a recall of Allergan textured implants, the ones most closely associated with ALCL, noted Deanna J. Attai, MD, of the Jonsson Comprehensive Cancer Center at UCLA in Los Angeles.

"As all national databases lag by several years, it is likely too soon to determine if the incidence of ALCL has decreased as a result of the recall," Attai, who was not involved in the analysis, told 乌鸦传媒 via email. "However, as the FDA has not recommended removal of textured implants in the absence of symptoms, women with textured implants should be aware that prior estimates of the risk of ALCL are lower than what is currently being reported."

The increased incidence of breast ALCL could be multifactorial, commented Catherine Diefenbach, MD, of NYU Langone Perlmutter Cancer Center in New York City, who was also not involved in the research.

"The authors hypothesize that an increase in the use of textured breast implants may be driving the rise in ALCL, as well as other factors such as improved detection and overall increase in breast lymphoma," she said. "These updated risk estimates should be discussed with all patients who are considering undergoing breast augmentation and should support continued regulatory surveillance of this procedure."

Historical Perspective

More than a , the FDA issued an initial safety communication about silicone gel-filled implants. In the year before the Allergan recall, the FDA noted a growing number of cases of implant-associated ALCL and released several months before asking Allergan to withdraw its textured breast implants from the market. Other makers of textured implants were not affected by the recall. The agency subsequently called for a boxed warning for all implants sold in the U.S.

Neither the recall nor the boxed warning recommended removal of breast implants in the absence of signs and symptoms. Population-based estimates of the incidence of breast ALCL in the U.S. have been lacking, Kinslow and co-authors noted. Authors of one of ALCL estimated that 3 million women in the U.S. had textured breast implants as of 2015.

In an effort to provide contemporary data on breast ALCL, the authors queried the Surveillance, Epidemiology, and End Results (SEER) database for 2001 through 2018. For external validation, they compared ALCL statistics in SEER and the National Program of Cancer Registries with FDA-reported cases.

For the entire study period, the analysis suggested more than a twofold higher case rate as compared with FDA estimates (8.1 vs 3.0/100 million). The data showed the incidence of breast ALCL increased from 3.2/100 million from 2000-2005 to 4.4/100 million from 2006-2011 to 14.5/100 million from 2012-2018. An analysis that included cases of T-cell lymphoma not otherwise specified resulted in an incidence of 19.6/100 million for 2012-2018.

The authors estimated that 353 cases of breast ALCL were diagnosed through 2017 by SEER data and 310 cases by the SEER/National Program of Cancer Registries data compared with 333 cases reported to the FDA over a similar period.

Lack of Guidance

No specific guidance has been issued with regard to ongoing follow-up of patients with textured implants, said Kinslow. The FDA has only advised women against removing an implant except as indicated by signs or symptoms of complications. The interval from implantation to diagnosis of ALCL has averaged 7 to 8 years.

"I definitely think it's a disease that a lot of clinicians aren't aware of, besides plastic surgeons, in terms of how clinicians are responding to this," he said. "Textured implants make up about 90% of the market in Europe, but in the U.S. it's much less. Silicone implants were banned in the U.S. for several years because of concern about an association with lymphoma, which has since been discredited. The U.S. was able to start using them again ... and they're still getting more popular. There are data indicating that use of textured implants has still been increasing in recent years."

The rising incidence of breast ALCL is noteworthy but "certainly not a cause for panic," said senior author David Horowitz, MD, also of Columbia University.

"We just hoped to inform not just the regulatory bodies but also physicians, as they're having discussions with their patients about risks for these rare sorts of complications," he said.

Correction: An earlier version of this article referred to ALCL as leukemia instead of lymphoma.

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