The results of a cohort study published in JAMA Network Open revealed an epidemiologic association between postmastectomy implant-based breast reconstruction for any breast tumor and both B- and T-cell non-Hodgkin lymphomas of the breast. According to Kinslow et al, this includes diffuse large B-cell lymphoma, small lymphocytic lymphoma, and peripheral T-cell lymphoma–not otherwise specified, as well as anaplastic large-cell lymphoma.
“We previously described an increase in the incidence of anaplastic large-cell lymphomas in association with breast implants; these adverse events have resulted in a black box warning by the U.S. Food and Drug Administration [FDA] on all breast implants,” the investigators commented. “Implant-associated anaplastic large-cell lymphoma has been attributed to chronic inflammation, which facilitates lymphoproliferation and malignant transformation within a hypoxic tumor microenvironment. Similar causes may contribute to the pathogenesis of other non-Hodgkin lymphomas, including B-cell lymphomas.”
Study Details
Using the Surveillance, Epidemiology, and End Results database, the investigators identified 61,043 women who underwent postmastectomy implant-based reconstruction for any breast tumor and had at least 12 months of follow-up from the date of their incident primary breast cancer diagnosis (median = 86 months). Of this population, 219 (0.4%) were American Indian or Alaska Native, 4,565 (7.5%) were Asian or Pacific Islander, 4,941 (8.1%) were Black, 6,227 (10.2%) were Hispanic, 44,947 (73.6%) were White, and 144 (0.2%) were reported as unknown. Patients were followed for the development of pathologically confirmed lymphomas until death, loss to follow-up, or the end of the study, with a 2-month latency exclusion period from the primary breast cancer diagnosis.
Key Findings
A total of 15 non-Hodgkin lymphomas of the breast (standardized incidence ratio [SIR] = 5.03, 95% confidence interval [CI] = 2.82–8.30) were diagnosed over 478,864 person-years, of which 7 were anaplastic large-cell lymphomas (SIR = 41.6, 95% CI = 16.7–85.8) and 8 were of other histologies (SIR = 2.84, 95% CI = 1.23–5.60). In the latter population, five diffuse large B-cell lymphomas (SIR = 5.26, 95% CI = 1.71–12.3), two small lymphocytic lymphomas (SIR = 16.7, 95% CI = 2.02–60.2), and one peripheral T-cell lymphoma–not otherwise specified (SIR = 11.8, 95% CI = 0.30–65.7) were reported. The investigators noted that five were diagnosed in the breast contralateral to the primary breast cancer. No patients reported receiving radiotherapy during their breast cancer treatment, whereas five underwent chemotherapy.
The median time from exposure to event was 83 months for breast anaplastic large-cell lymphoma (excess risk: 14.3 cases per 1,000,000 persons per year) and 82.5 months for other non-Hodgkin lymphomas (excess risk: 10.8 cases per 1,000,000 persons per year). The excess risks of diffuse large B-cell lymphoma, small lymphocytic lymphoma, and peripheral T-cell lymphoma–not otherwise specified were 8.5, 3.9, and 1.9 cases per 1,000,000 persons per year, respectively. Increased risks of non-Hodgkin lymphoma outside the breast and Hodgkin lymphoma of the breast were not reported. The risk of non-Hodgkin lymphoma of the breast was not found to be increased in patients who received mastectomy without immediate implant-based reconstruction (SIR = 1.31, 95% CI = 0.91–1.83) or lumpectomy with or without radiotherapy (SIR = 1.11, 95% CI = 0.78–1.52).
Limitations included the inability to evaluate women with cosmetic implants or noncancer-related surgeries in the contralateral breast. The investigators recommended that future studies further explore the pathophysiology, presentation, patient- and implant-specific risk factors, and treatment of these malignancies.
They concluded, “It is important to appreciate that the absolute risk of lymphoma is extremely low and similar for anaplastic large-cell lymphoma and the other non-Hodgkin lymphoma histologies. We and others have not identified an elevated risk of breast squamous cell carcinoma, another implant-associated malignant neoplasm identified by the FDA, following implant-based breast reconstruction. The FDA is aware of fewer than 30 cases of non–anaplastic large-cell lymphomas in breast implant capsules vs over 1,300 cases of anaplastic large-cell lymphoma. Continued surveillance of breast implant–associated malignant neoplasms is warranted by government and regulatory agencies.”
Alfred I. Neugut, MD, PhD, of Columbia University Irving Medical Center, New York, is the corresponding author of the JAMA Network Open article.
Disclosure: The study was funded by a grant from the National Cancer Institute and a Cancer Center Support Grant. For full disclosures of the study authors, visit jamanetwork.com.
