BRCA1/2 MUTATIONS IMPACT ON THE DEVELOPMENT OF BREAST IMPLANT‐ASSOCIATED LYMPHOMA (BIA‐ALCL) IN WOMEN WITH BREAST CANCER RECONSTRUCTED WITH TEXTURED BREAST IMPLANTS

Abstract

Introduction: Breast Implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a subtype of T-cell lymphoma arising as a seroma and/or mass in relation to the capsule of textured breast implants. Previous research in a Dutch population suggests a higher-than-expected prevalence of BRCA1/2 carriers in women with BIA-ALCL. Here we analyze the risk of BIA-ALCL occurrence related to BRCA in a large population of women with implants followed long term after breast cancer (BC) mastectomy. Methods: We compared the prevalence of BRCA1/2 pathogenic variants (pv) between women from a large cohort of BC patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) who did and did not develop BIA-ALCL after reconstruction with textured implants. Hazard ratios (HRs) of developing BIA-ALCL were estimated using Cox regression. To best control for age at BC diagnosis and length of follow up, we conducted a nested case-control within the cohort, matching 1:3, analyzed with conditional logistic regression. Results: Among 3312 women with BC assessed for pv in the context of MSK-IMPACT tumor and normal study at MSKCC the prevalence of BRCA mutations was 5.3%. Among 526 patients with textured implants post BC mastectomy, followed long term at MSKCC (median FU 82 mo, range 12, 316) and clinically assessed for BRCA1/2, the prevalence of pv of BRCA1/2 was 7.8%. Of 31 BIA-ALCL post-BC cases seen at MSKCC, 16 received capsulectomy at MSKCC and 5/13 (38.4%) were BRCA1–2 positive. Within the cohort of 526 patients with BC tested for BRCA, reconstructed with textured implants and followed long-term, the age-adjusted rate of developing BIA-ALCL for women with BRCA mutations was 11.0 times the rate of BIA-ALCL among women without BRCA (HR 95% CI 3.6, 33.9, p < .0001). Carrying bilateral versus unilateral implants (HR 6.9, 95% CI 0.9, 53.2), prior chemotherapy exposure (HR 0.7, 95% CI 0.2, 2.05), prior radiation therapy exposure (HR 0.5, 95% CI 0.1, 2.5) were not significantly associated with the rate of BIA-ALCL. Within this cohort, 13 BIA-ALCL cases were matched 1:3 with 39 controls. Median ages at BC mastectomy were 47.2 (37, 66) and 46.8 (35, 65) in cases and controls, respectively. The median time between reconstruction for BC and BIA-ALCL was 130 (80, 190) months. The odds ratio of BIA-ALCL associated with carriership of a BRCA1/2 pathogenic variant was 12.4 (Wald 95% CI 1.4, 109.5 p = 0.0074). Conclusions: In this study, we define the role of BRCA1/2 mutations as a significant risk factor in the development of BIA-ALCL in patients with BC reconstructed with textured implants. These results will help decision making for women with BRCA1/2 mutations undergoing breast reconstruction, or with textured implants in place. Analysis of pathogenic variants in other DNA repair genes in this cohort potentially affecting lymphomagenesis is ongoing. The research was funded by: NIH R03 grant number R03CA267435 Keywords: aggressive T-cell non-Hodgkin lymphoma, prevention and cancer interception No conflicts of interests pertinent to the abstract.