Breast implants are associated with an increased risk — albeit small — of anaplastic large-cell lymphoma (ALCL) in the breast, according to Dutch researchers.

The results of the study, led by Mintsje de Boer, MD, of Maastricht University Medical Centre in the Netherlands, were published in JAMA Oncology.

The researchers, therefore, performed a case-controlled study to determine the relative and absolute risks of breast-ALCL in women with implants.

Using the population-based nationwide Dutch pathology registry, de Boer and colleagues were able to identify patients diagnosed with primary non-Hodgkin lymphoma in the breast between 1990 and 2016 and then retrieved their clinical data, including breast implant status.

Among the 43 patients with breast-ALCL (median age of 59), 32 had an ipsilateral breast implant (median age of 56) compared with only one patient among 146 women with other primary breast lymphomas, resulting in an OR of 421.8 (95% CI, 52.6-3385.2) for breast-ALCL associated with a breast implant.

The investigators also examined the connection between specific types of implants and breast-ALCL. Of the 28 patients with breast-ALCL with a known implant type, 23 (82%) had macrotextured implants, which was more than expected considering that less than half (45%) of implants sold in the Netherlands between 2010 and 2015 were macrotextured.

The cumulative risk of breast-ALCL in the general population increased with age, reaching about 0.35 per million at the age of 75. For women with implants, the cumulative risk increased from about 29 per million at age 50 to about 82 per million at age 70. De Boer and colleagues calculated that the number of women with implants needed to cause one breast-ALCL case before the age of 75 was 6,920.

“Our relative risk estimate of over 400, implying an attributable risk approaching 100%, is highly suggestive of a direct or indirect causal role of the breast implant-associated ALCL,” de Boer and colleagues wrote.

They also pointed out that their calculations concerning the absolute risk of breast-ALCL has multiple implications considering the relatively large number of women (3.3%) in the Netherlands having implants. These include the need for comprehensive counseling of women considering having breast implants for cosmetic or reconstructive surgery, alternative cosmetic/reconstruction procedures, and the establishment of a registry program for breast implants and their complications.

As for the study limitations, de Boer et al noted that retrospective data on the prevalence of breast implants were not available because of an absence of breast implant registration — which only began in the Netherlands in 2016 — and the lack of reliable and complete historical implant sales data.

“Therefore our absolute risks of breast-ALCL in implant carriers were based on extrapolated data. Even in this nationwide study, numbers were too small to allow definite conclusions on modifying factors, such as duration of implant exposure and implant types.”

In an accompanying commentary, Colleen M. McCarthy, MD, and Steven M. Horwitz, MD, both of Memorial Sloan Kettering Cancer Center in New York City, wrote that while de Boer and colleagues should be commended for their “rigorous approach” to defining the risk of breast-ALCL in patients with implants, the conclusions appear to “more confirmatory than new.”

For example, as noted in this article in MedPage Today, the FDA earlier this year affirmed a link between ALCL and breast implants, and suggested that women with implants should be regularly monitored for signs and symptoms of the disease.

De Boer et al “conclude that breast implants are associated with a strongly increased relative risk of breast-ALCL, yet the absolute risk of the disease presented here remains extremely low,” McCarthy and Horwitz wrote, pointing out that most women with implants newly diagnosed with ALCL are successfully treated with implant removal and capsulectomy alone.

“For a woman and her physician considering options for implant-based surgeries, differences in underlying beliefs and values among women will sway decision making in different directions. Thus, when considering options where there is uncertainty, it is particularly important that the process of decision-making be shared, because these decisions are highly dependent on individual patient preferences and assessment of risk.”