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Tuesday, June 17, 2025

BRCA Mutations Hike Risk of Rare Breast Implant-Associated Lymphoma

 Patients with BRCA-mutant breast cancer had a significantly higher risk of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL), a large cohort study showed.

BRCA1/2 mutations conferred a 16-fold increased risk of BIA-ALCL in women who received textured breast implants as part of breast reconstruction. The association between BRCA mutations and BIA-ALCL persisted in a secondary case-control analysis to rule out a non-association.

The findings confirm and build on those of a previous Dutch study and should help inform discussions with patients who have textured implants, reported Paola Ghione, MD, of Memorial Sloan Kettering Cancer Center in New York City, and coauthors in Blood Advancesopens in a new tab or window.

"If we look at the absolute numbers [of BIA-ALCL] it's still fairly rare, but the important thing to note is that when we look at women with this genetic predisposition, there is a big jump in the percentage with this lymphoma," Ghione said in a statementopens in a new tab or window.

Textured implants linked to lymphoma were withdrawn from the U.S. market in 2019opens in a new tab or window, but many women still have the implants in place. The FDA does not recommend implant removal from women who are asymptomatic.

"The implants that are put in place now are theoretically safe," said Ghione. "However, there are still a lot of women who are living with textured breast implants, so it's important that women know what implants they have, talk with their doctor, and remember to report this surgery as part of their medical history."

The finding that BRCA carriers have an increased risk of BIA-ALCL is not particularly surprising, said Kelly Hunt, MD, of the University of Texas MD Anderson Cancer Center in Houston. BRCA pathogenic variants increase the risk of developing several types of cancer, including ovarian and pancreaticopens in a new tab or window, in addition to breast cancer.

"The condition is already rare and they were looking at a subgroup of patients who have the condition, so the numbers are small," Hunt told MedPage Today. "The important point of this study is to make sure that women who still have the implants are aware of the risks and tell their doctors about any symptoms that might be related to the implants."

Textured implants were used much more commonly outside the U.S. and are still available in some countries, so the global number of women potentially at risk of BIA-ALCL is fairly large, she added. Symptoms of BIA-ALCL include pain, lumps, swelling, or unexpected changes in breast shape. At least one recent case was identified in a woman who had discomfort and swelling in a lymph node.

The earliest documented caseopens in a new tab or window of BIA-ALCL was reported in 1997. In 2011, the FDA reported a "possible association"opens in a new tab or window between breast implants and ALCL. Since then, multiple reports have documented a growing number of cases. In its most recent updateopens in a new tab or window on the issue, the FDA reported a total of 1,380 reported cases worldwide and 64 deaths attributable to BIA-ALCL.

A potential link between BRCA pathogenic variants and ALCL emerged within the past 5 years. Investigators in the Netherlandsopens in a new tab or window reported a higher prevalence of germline BRCA1/2 mutations in patients with BIA-ALCL versus the overall Dutch population (26.7% vs 0.5%). Then Ghione and colleagues published a study showing a BIA-ALCL incidenceopens in a new tab or window of one case per 322 women with textured breast implants, substantially higher than reported rates for the general population.

"However, our high-risk estimate for BIA-ALCL might be related to characteristics of our population that have not yet been identified, including a relatively high prevalence of germline mutations," the authors acknowledged.

To examine more closely the relationship between BRCA1/2 mutations and BIA-ALCL risk, investigators analyzed data for 520 women with breast cancer and implants, all tested for BRCA status. During a median follow-up of 138 months, seven patients developed BIA-ALCL.

The data showed that 43 (8.3%) of the patients tested positive for BRCA pathogenic variants. Comparison of patients with and without BRCA pathogenic variants showed that the risk of BIA-ALCL was 16 times higher in patients with germline BRCA mutations (95% CI 3.6-76.1, P<0.0003).

To explore the association between BRCA status, implants, and ALCL, Ghione and colleagues performed a case-control study comparing 13 women with BIA-ALCL (six outside of the 520-patient cohort) and a control group of 39 women with breast implants and no BIA-ALCL. The results showed that five of the 13 patients (38.5%) with BIA-ALCL had BRCA pathogenic variants versus three of the 39 patients (7.8%) in the control group.

"The number of cases in our cohort is very small, which is certainly related to the rarity of the disease, and this might impact the reliability of our estimate," the authors acknowledged. "The 95% confidence interval for the HR [hazard ratio] calculated in our analysis is statistically significant but quite wide, indicating that there is an association of BRCA1/2 pathogenic variants with BIA-ALCL development, but the real weight of this association is still to be defined."

Disclosures

The study was supported by the National Cancer Institute.

Ghione and co-investigators reported no relevant relationships with industry.

Hunt has disclosed relationships with Leica Microsystems, Merck, and AstraZeneca.

Primary Source

Blood Advances

Source Reference: opens in a new tab or windowGhione P, et al "BRCA1/2 impact on the development of implant-associated lymphoma in women with breast cancer and textured implants" Blood Adv 2025; DOI: 10.1182/bloodadvances.2025016810.


https://www.medpagetoday.com/hematologyoncology/lymphoma/116126

'Gilgo Beach murders tied to Heuermann by ‘unreliable’ DNA software, needed ‘updates’ for glitches'

 The DNA software that linked Rex Heuermann to the Gilgo Beach murders was so glitchy that it was updated multiple times after it tied the accused serial killer to the grisly murders, a defense expert testified Tuesday.

Nathaniel Adams, a biotechnology expert for Heuermann’s defense team, testified at a fiery court hearing that the IDBGEM program was prone to misreading genotype data that was used to link the suspected killer to six of the seven sex workers butchered and dumped on Long Island over more than 30 years.

“It’s unreliable,” Adams, a 27-year-old graduate student and systems engineer for Forensic Bioinformantics in Ohio, testified in Suffolk County court. “The software has been updated multiple times since the DNA in this case has been tested.”

Rex Heuermann, in court with lawyer Michael Brown, is charged with seven Long Island cold case killings.Newsday

He said the software bugs would require a “risk and hazard analysis” to avoid a “catastrophic failure” that could lead to “a miscarriage of justice.”

Adams revealed there here have been 65 small updates, and that even newer software versions of the program have dropped since June 2020, when they tested Heuermann and his family’s DNA.

But Suffolk County District Attorney Ray Tierney scoffed at Adams’ qualifications as an expert on DNA — maintaining his testimony in about 30 other court cases have often been deemed “inadmissible.”

“You’ve been in school for 10 years and have only obtained a bachelor’s degree in all this time?” Tierney said as he grilled Adams on the stand. “You’re supposed to be an expert, but you don’t even know who your adviser was or if you graduated summa cum laude or not.”

DNA is crucial to the prosecution’s case as the most direct link to Heuermann and the killings.

Expert DNA witness Nathaniel Adams testified that DNA software used in the Gilgo Beach killings is unreliable.James Messerschmidt
The seven sex workers allegedly killed by accused Long Island serial killer Rex Heuermann between 1993 and 2010.Suffolk County Police Department

Suffolk prosecutors said they have linked Heuermann, a 61-year-old Manhattan architect from Massapequa Park, through hairs found on the seven victims. They were all sex workers who disappeared between 1993 and 2010 and were later found along desolate stretches of Long Island.

The deaths of the victims — Valerie Mack, 24, Taylor, 20, Megan Waterman, 22, Melissa Barthelemy, 24, Maureen Brainard-Barnes, 25, Sandra Costilla, 28, and Amber Lynn Costello, 27 — remained unsolved until authorities reopened the cold case in 2022.

Heuermann, a married father of two, was arrested in July 2023 for three of the murders and was later tied to the other four through the DNA matches.

Investigators matched some of the victims through DNA links to Heuermann’s wife, Asa Ellerup, and his adult daughter, Victoria Heuermann, authorities said.

Authorities have searched Rex Heuermann’s Massapequa Park home twice searching for evidence in the killings.New York Post
Suffolk County DA Ray Tierney scoffed at the credentials of the DNA witness called by Rex Heuermann’s lawyer.Dennis A. Clark

Authorities have twice executed search warrants at the Heuermann home, combing through the property, digging up the back yard and testing a basement gun bunker prosecutors believed was a “kill room” — but have not revealed finding any physical evidence.

The DA did uncover a sick computer file, described as a “how to” record on some of the killings and notes that appear to provide tips on how to improve the slayings.

The high-profile serial murder case has captured the nation’s imagination, and is the subject of a newly released three-part Peacock docu-series that features first-ever interviews with Heuermann’s family.

https://nypost.com/2025/06/17/us-news/gilgo-beach-murders-tied-to-rex-heuermann-by-dna-software-that-needed-updates-due-to-glitches-expert-testifies/