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Low-level expression of human Epidermal growth Factor Receptor-2 (HER2) in High-Grade Mullerian Tumors: Implications for therapy decision making

INTRODUCTION: Reclassification of HER2-negative breast cancers to HER2 low-level expression allowed targeted anti-HER2 therapy in about 60% of patients, improving outcome. The high recurrence rates and often dismal outcomes with current therapies of high-grade Mullerian carcinomas, offers opportunit...

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Detalles Bibliográficos
Autores principales: Abada, Evi, Singh, Kamaljeet, Hansen, Katrine, Quddus, M. Ruhul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432814/
https://www.ncbi.nlm.nih.gov/pubmed/37600081
http://dx.doi.org/10.1016/j.gore.2023.101251
Descripción
Sumario:INTRODUCTION: Reclassification of HER2-negative breast cancers to HER2 low-level expression allowed targeted anti-HER2 therapy in about 60% of patients, improving outcome. The high recurrence rates and often dismal outcomes with current therapies of high-grade Mullerian carcinomas, offers opportunity to explore anti-HER2 therapies in the gynecologic tract carcinomas. We investigated HER2 low expression as currently defined in breast carcinomas. METHODS: We reviewed all high-grade Mullerian cancers between 2016 and 2021, where HER2 by IHC and/or FISH tests were available. Additional clinical information was recorded, and statistical analysis was performed using SPSS (version 27). RESULTS: Forty (49.4%) tumors were endometrial, 20 (24.7%) ovarian, 16 (19.8%) fallopian tubal, and 5 (6.2%) primarily peritoneal. Overall, 17 (21.0%) were HER2 positive (IHC 3+/IHC 2+/FISH amplified), 31 (38.3%) HER2 low (IHC 1+/2+/FISH non-amplified), and 30 (37.0%) were HER2 negative (IHC = 0). HER2 low expression was noted in 15% ovarian, 25% fallopian tubal, 53% endometrial, and 60% peritoneal tumors; 34% and 21% of serous carcinomas, 63% and 13% of carcinosarcomas, and 67% and 33% of endometrioid carcinomas were HER2 low and HER2 positive respectively. HER2 negative and HER2 low expression had a significant association with primary tumor location (p = 0.001); endometrium and peritoneal tumors were more likely to be HER2 low and HER2 negative. During a mean follow-up of 13.2 months (range: 1–34), 5% of the patients were deceased. CONCLUSIONS: Based on the current HER2-low recommendations in the breast, about one-third of patients with high-grade Mullerian carcinomas might qualify for anti-HER2 therapy with a potential for improved progression-free and overall survival.