Implant replacement and anaplastic large cell lymphoma associated with breast implants: a quantitative analysis
Authors: Martina Vittorietti, Sergio Mazzola, Claudio Costantino, Daniele Domenico De Bella, Santo Fruscione, Nicole Bonaccorso, Martina Sciortino, Davide Costanza, Miriam Belluzzo, Alessandra Savatteri, Fabio Tramuto, Paolo Contiero, Giovanna Tagliabue, Palmira Immordino, Francesco Vitale, Arianna Di Napoli, Walter Mazzucco
Journal: Front Oncol (2023)
Keywords: anaplastic large cell lymphoma associated with breast implants, breast implants replacement, epidemiology, quantitative analysis, time to disease onset, treatment outcomes
MeSH terms: Systematic Review

Introduction:
Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin T-cell lymphoma associated with breast reconstruction post-mastectomy or cosmetic-additive mammoplasty. The increasing use of implants for cosmetic purposes is expected to lead to an increase in BIA-ALCL cases. This study investigated the main characteristics of the disease and the factors predicting BIA-ALCL onset in patients with and without an implant replacement.
Methods:
A quantitative analysis was performed by two independent researchers on cases extracted from 52 primary studies (case report, case series, and systematic review) published until April 2022 and searched in PubMed, Scopus, and Google-Scholar databases using "Breast-Implant" AND/OR "Associated" AND/OR "Anaplastic-Large-Cell-Lymphoma". The statistical significance was verified by Student's t-test for continuous variables, while Fisher's exact test was applied for qualitative variables. Cox model with time-dependent covariates was used to estimate BIA-ALCL's onset time. The Kaplan-Meier model allowed the estimation of the probability of survival after therapy according to breast implant exposure time.
Results:
Overall, 232 patients with BIA-ALCL were extracted. The mean age at diagnosis was 55 years old, with a mean time to disease onset from the first implant of 10.3 years. The hazard of developing BIA-ALCL in a shorter time resulted significantly higher for patients not having an implant replacement (hazard ratio = 0.03; 95%CI: 0.005-0.19; p-value < 0.01). Patients with implant replacement were significantly older than patients without previous replacement at diagnosis, having a median time to diagnosis since the first implant of 13 years (7 years in patients without replacement); anyway, the median time to BIA-ALCL occurrence since the last implantation was equal to 5 years.
Discussion:
Our findings suggest that, in BIA-ALCL patients, the implant substitution and/or capsulectomy may delay the disease's onset. However, the risk of reoccurrence in an earlier time should be considered in these patients. Moreover, the time to BIA-ALCL onset slightly increased with age. Selection bias, lack of awareness, misdiagnosis, and limited data availability could be identified as limits of our study. An implant replacement should be considered according to a risk stratification approach to delay the BIA-ALCL occurrence in asymptomatic patients, although a stricter follow-up after the implant substitution should be recommended.
Systematic review registration:
https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42023446726.