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 Advances.
"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 statement.
Textured implants linked to lymphoma were withdrawn from the U.S. market in 2019, but many women still have the implants in place.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 pancreatic, 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 case of BIA-ALCL was reported in 1997. In 2011, the FDA reported a "possible association" between breast implants and ALCL. Since then, multiple reports have documented a growing number of cases. In its most recent update 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 Netherlands 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 incidence 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: Ghione 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
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